If the patient develops signs of respiratory compromise, there should be no

hesitation in proceeding with endotracheal intubation of the patient and

providing mechanical ventilatory support until the drug effects have
dissipated. If subcutaneous injection occurs in patients receiving baclofen,
the patient may exhibit signs of overdose including CNS depression,
somnolence, hallucinations, agitation, mydriasis, nausea and vomiting and
may progress to severe bradycardia, hypotension, and respiratory failure. If
baclofen overdose is suspected, immediate admission to the hospital is
warranted. These patients should be closely monitored and can require
supportive care to maintain hemodynamic and respiratory function. A
nonspecific reversal agent for baclofen overdose is physostigmine which
should be administered in incremental doses.

PHARMACOLOGIC COMPLICATIONS AND DRUG-

RELATED SIDE EFFECTS
Side Effects of Intrathecal Opioids
It is commonly held misconception that switching from systemic to IT
delivery of opioids alleviates all of the clinically significant side effects.
However, IT opioid infusion is commonly associated with side effects.
Often, these side effects are mild and well tolerated and do not interfere
with therapy. As patients develop tolerance to the analgesic effects of the
drug, they also tend to develop tolerance to the side effects. Nonetheless,
some patients develop side effects that may be so bothersome as to have a
significant impact on the treatment. The most common side effects
experienced by patients receiving IDDS include respiratory depression,
gastrointestinal symptoms, urinary dysfunction, hormonal alterations, and
itching.
Aside from true anaphylaxis, which is rare with the use of opioids,
respiratory depression is the most clinically concerning drug-related side
effect. Respiratory depression results from the supraspinal interaction of
the drug with µ-opioid receptors in the brainstem. It can occur from rostral
spread of the drug and is probably more common when using hydrophilic
agents which can attain significant concentrations in the CSF. Respiratory
depression can also occur with systemic absorption from the CSF into the
blood and redistribution to the CNS. It is most likely to occur in patients

5001
who are opioid naive. There are relatively few reports of clinically
significant respiratory depression in patients who have been exposed to
opioids before instituting IDDS. Additional risk factors for development of
respiratory depression include advanced age, absence of severe pain,
debilitated physical condition, preexisting pulmonary disease, sleep apnea,
and use of additional opioids delivered by alternative routes. Respiratory
depression can occur as early as 4 hours following IT dosing, although it is
often delayed in onset up to 24 hours. Treatment consists of support of
respiration and the judicious use of a µ-receptor antagonist such as
naloxone and employing appropriate precautions as outlined previously in
this chapter.45
Urinary retention is another common side effect of IT opioids, reported
in 20% to 40% of patients. It is a direct spinal side effect caused by
reduction in detrusor muscle tone and detrusor-urethral sphincter
dyssynergia. It does occur with the intraventricular administration of
morphine. It is believed to be mediated primarily through µ- and δ-
receptors. It is more common in males and rare in women and individuals
who are opioid tolerant. It is often self-limited and usually resolves within
24 to 48 hours. Treatment entails intermittent bladder catheterization until
the problem resolves. One can also consider adjunct pharmacologic
treatment with opioid antagonists and/or phenoxybenzamine. If the
problem persists, an alternative strategy involves switching to another
opioid.45
Gastrointestinal side effects such as nausea, vomiting, and constipation
are less common than with systemic delivery. However, they still occur in
up to 25% to 30% of patients, especially those who are opioid naive.
Nausea and vomiting are mediated by the interaction of opioids with the
chemoreceptor trigger zone. Treatment is usually symptomatic with
antiemetic agents.
Pruritus occurs in about 25% of patients exposed to IT opioids and may
be more common in opioid-naive individuals. It is more common with
morphine than other opioids and is believed to result from degranulation of
mast cells. The problem is usually self-limited and can be managed with
antihistamines albeit with mixed results. In the case of severe persistent
itching, the best approach is to switch to an alternative opioid such as

5002
hydromorphone or fentanyl. It is important to differentiate opioid-induced
pruritus from true allergy. Most patients and many clinicians not familiar
with the actions of IT opioids will misconstrue itching as an allergic
reaction. In fact, true allergic reactions to morphine or its congeners is
unusual.45
Finally, there is compelling evidence that opioids can have a negative
effect on neuroendocrine function.46 Morphine has been shown to inhibit
the release of gonadotropin- and corticotrophin-releasing hormones from
the hypothalamus, resulting in reduced circulating levels of luteinizing
hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic
hormone (ACTH), and β-endorphin. The end result is reduction in serum
levels of cortisol and testosterone. Clinically, the end effect is reduction in
libido and/or impotency. In men, reductions in testosterone can also result
in decreased muscle mass and increased fat mass. In addition to these
effects, IT morphine administration can also produce significant fluid
retention, likely due to alterations in antidiuretic hormone function.

Opioid Tolerance
Tolerance can be defined as the requirement for progressively escalating
doses of medication in order to achieve the same degree of clinical effect.
In pharmacologic terms, tolerance represents a pharmacodynamic effect
manifested by a rightward shift in the dose–response curve. Two
mechanisms for opioid tolerance have been proposed: desensitization (i.e.,
decreased activation) of opioid receptors following prolonged exposure to
opioids and opioid receptor downregulation.7 Desensitization involves
changes in opioid receptor physiology that are believed to result from
alterations in G-protein coupled receptor (GPCR) function. The end result
is a decrease in analgesia. Like many other GCPRs, downregulation, the
second mechanism believed to produce opioid tolerance occurs when
opioid receptors are internalized from the cell membrane by endocytosis,
is mediated through the β-arrestin pathway.
Although tolerance is discussed mostly in terms of loss of analgesia, it
should be noted that tolerance also occurs to other effects of a given drug.
Tolerance is believed to be an important causal factor in the loss or
complete failure of analgesia in patients with implanted drug delivery

5003
systems, particularly those patients primarily receiving opioid medications.
Tolerance usually develops over the course of time, and the rate at which
tolerance develops may vary between individuals. Moreover, tolerance
does not usually develop equally to all effects of a given drug at the same
rate. Before concluding that loss of analgesia is indeed related to tolerance,
it is important for the clinician to exclude other reasons such as problems
with the delivery system or progression of disease.
Management of tolerance depends to large degree on the baseline
treatment protocol for a given patient.45 In some cases, simple dose
titration by 10% to 30% per day will overcome the problem. If indeed the
problem is simply a tolerance issue, then increasing the dose should result
in demonstrably improved pain control, at least for some period of time.
Depending on the delivery system, dose escalation will be limited by the
volume that can be safely infused. The maximum infusion rate generally
recommended for an epidural infusion is around 10 to 15 mL per hour; for
IT infusion, the rate should not exceed more than 10% of the patient’s
calculated CSF volume (typically 75 mL total, limiting the daily infusion
to 7.5 mL per day). These limitations can make restoration of analgesia
impossible by dose titration alone unless the infusion prescription can be
prepared in a higher concentration, although there are also limits to this
(Table 100.7).

TABLE 100.7 Current Suggested Dose and Concentration

Limitations for It Drug Delivery
Drug Maximum Concentration Maximum Daily Dose
Morphine 20 mg/mL 15 mg/d
Hydromorphone 10 mg/mL 4 mg/d
Fentanyl 2 mg (2,000 µg)/mL Unknown
Sufentanila 50 µg/mL Unknown
Bupivacaine 40 mg/mL 30 mg/d
Clonidine 2 mg (2,000 µg)/mL 1.0 mg (1,000 µg)/d
Ziconotideb 100 µg/mL 19.2 µg/d
aSufentanil is not available for compounding.
bMaximum daily dose based on recommendations of Jazz Pharmaceuticals.
From Deer T, Krames EJ, Hassenbusch SJ, et al. Polyanalgesic consensus conference 2007:
recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of
an interdisciplinary expert panel. Neuromodulation 2007;10(4):300–328. Adapted by permission

5004
 of John Wiley & Sons, Inc.

It has been suggested that continuous drug delivery is less likely or will
less rapidly lead to the development of tolerance, although there are no
studies that clearly demonstrate this to be the case. Switching to a more
potent opioid may result in a slower development of tolerance by reducing
the rate of receptor downregulation. One can also consider switching to a
different opioid assuming there is incomplete cross tolerance between the
two drugs. Another strategy is to add other agents such as clonidine that
act through alternative spinal modulating systems and therefore might
have some opiate-sparing effects. Finally, some experts have suggested
that a local anesthetic be substituted for the opioid to provide for an
opioid-free interval.

Intrathecal Inflammatory Masses (Intrathecal Granuloma)

Inflammatory masses associated with the tip of an IT catheter is a
potentially serious complication that, if not promptly recognized and
managed, can result in neurologic injury. IT granuloma was first reported
in 1991 and, over the course of time, additional case reports and small case
series appeared in the literature. By 2000, 41 cases had been reported. Due
to growing concern about this problem, a consensus panel met and
subsequently published recommendations on the management of catheter-
tip inflammatory masses. A similar consensus panel was reconvened in
2007 and the recommendations and guidelines of this panel were recently
published.47 The panel reviewed the pertinent literature including
preclinical data, information on pathophysiology of inflammatory mass
formation, and clinical data, and ultimately developed an algorithm for
prevention, early detection, and treatment.
An inflammatory catheter tip mass typically is composed of both acute
and chronic reactive inflammatory cells derived from the arachnoid and/or
fibrosis that does not directly involve the spinal cord parenchyma.
Although these masses represent a buildup of granulation tissue and have
been termed “granulomas,” they do not fit the classical histopathologic
description of a true granuloma. An infectious agent has never been
associated with these inflammatory masses. There are a number of
preclinical studies in both dogs and sheep that demonstrate that catheter-tip

5005
inflammatory masses occur predictably in animals receiving IT morphine
infusions. Based on preclinical studies, the panel concluded that these
masses likely occurred as a result of infusion of high concentrations and/or
high daily doses of IT morphine.
Although most of the preclinical evidence implicated the use of
morphine, more recent data indicate that other opioid infusions may be
associated with inflammatory catheter tip masses. There has also been a
more recent report implicating IT baclofen as a potential causative agent.
Although the occurrence of inflammatory masses in humans is less
predictable than in animal models, it is believed that the incidence in
humans increases with the duration of IT therapy, ranging between 0.4%
after 2 years of treatment up to 1.16% after 6 years of treatment.
Moreover, animal data fails to clarify whether there is dose in humans
below which granuloma formation will not occur. Available data do
support the concept that both concentration and total dose of all opioids,
with the exception of fentanyl, are important in the development of
inflammatory masses. Based on the available data, the 2007 consensus
panel has published recommendations for maximum doses and
concentrations of the currently used IT agents (see Table 100.7).
The first clinical clue of the development of an inflammatory catheter
tip mass in a patient who has otherwise been doing well is often an
increase in the patient’s pain and the requirement for repeated and rapid
dose escalations. In such cases, absent an obvious progression of disease,
one should begin to consider that diagnosis of an inflammatory mass. Any
patient who develops new neurologic symptoms should be evaluated with
spinal imaging, preferably MRI. A catheter-tip inflammatory mass can
usually be detected with MRI (Fig. 100.5).

5006
FIGURE 100.5 Magnetic resonance imaging (MRI) study of a patient with an inflammatory mass
surrounding the tip of an implanted intrathecal drug delivery catheter. A: Midline, sagittal, T2-
weighted image. The inflammatory mass involves the dorsal aspect of the spinal cord at the level of
the inferior end plate of T10. B: Axial, T2-weighted image through the inflammatory mass. The
mass displaces the spinal cord toward the left. (Reprinted with permission from Ferrante FM,
Rathmell JP. Complications associated with intrathecal drug delivery systems. In: Neal JM,
Rathmell JP, eds. Complications in Regional Anesthesia and Pain Medicine. Philadelphia, PA:
Lippincott Williams & Wilkins; 2013:279. Figure 25-7.)

Management of the patient with an inflammatory catheter tip mass

depends on the clinical situation but is primarily related to the presence or
absence of neurologic signs and/or symptoms. If a mass is detected and the
patient does not have neurologic symptoms, it is possible to retract the
catheter caudally a few centimeters out of the granuloma and reduce the
drug dose and/or concentration. One additional suggestion has been to
switch to a “safer” medication such as fentanyl or ziconotide. If symptoms
persist despite these changes, the patient should be rapidly weaned off all
IT opioids, the medication should be removed from the pump, and the
pump filled with saline. One needs to pay close attention to signs of
withdrawal, not only from opioids but also from adjuvant medications that
may also be in the pump such as clonidine and/or baclofen. If the
symptoms resolve after removing the catheter from the mass, the patient
should be reimaged in 6 months to confirm resolution of the granuloma
before reinstituting the therapy. If a small granuloma is still evident, one
must decide between further retraction or removal of the catheter. If
neurologic signs and symptoms persist or in the event that a granuloma is
detected that is producing significant neural compression, then the system
should be removed. In patients with a large granuloma compressing the
spinal cord and producing neurologic dysfunction, consultation with a

5007
neurosurgeon should be obtained to determine whether removal of the
granuloma itself is warranted.

Drug Withdrawal
Disruption of the IT catheter, pump battery failure, and human error during
refill and reprogramming can all lead to sudden cessation of drug delivery
and result in drug withdrawal. Of the medications that are currently used
for IT delivery, distinct abstinence syndromes are most commonly
associated with opioids, baclofen, and clonidine. There are currently no
reports of withdrawal associated with the use of IT ziconotide.
The clinical symptoms and signs associated with opioid withdrawal
include any or all of the following: increased lacrimation and rhinorrhea,
diaphoresis, mydriasis, pilomotor erection, restlessness, irritability or
agitation, gastrointestinal symptoms (nausea, vomiting, diarrhea), tremor,
abdominal cramping, and, of course, increased pain levels.45 In severe
cases, acute opioid withdrawal can lead to pulmonary edema or
cardiovascular collapse resulting in death. The most common causes of
opioid withdrawal are catheter disruption and pump refill/programming
errors. Because of the risk of opioid withdrawal, antagonist medication
must be used with caution in patients undergoing chronic opioid therapy.
Treatment should be aimed at respiratory and hemodynamic support with
restoration of the drug infusion as soon as possible.
Baclofen withdrawal is a serious complication that, if unrecognized, can
be life-threatening. It is usually heralded by increase in spasticity,
sometimes to the point of rigidity, pruritus, hyperthermia, drowsiness
progressing to obtundation, respiratory depression, rhabdomyolysis, acute
renal failure, acute multiorgan failure, and even death.45 Early recognition
is the key to treatment. The treatment of baclofen withdrawal requires
urgent attention, the goal being restoration of the IT baclofen infusion as
soon as possible. For patients with signs of severe baclofen withdrawal, it
is not sufficient to merely provide oral medication until the problem can be
fixed. In such cases, it may be prudent to place a temporary lumbar drain
and restart the infusion until such time as the problem can be correctly
diagnosed and treated. Abrupt cessation of clonidine can also be associated
with adverse effects such as rebound hypertension, particularly in patients

5008
receiving higher doses. All patients receiving clonidine should be provided
a prescription for either oral or transdermal clonidine and advised to
contact the implanting physician should they develop any symptoms or
signs of clonidine withdrawal.

Patient Outcomes and Intrathecal Drug Infusion

CANCER PAIN
Continuous IT infusion of opioids was first used for the management of
cancer pain in the early 1980s and, over the next decade, remained the
single most common indication for IDDS. During the past several years, it
seems the use of IT opioids for cancer pain has declined due in large
measure to the development of more effective long-acting oral opioids as
well as the development of less expensive drug infusion reservoirs.
Nevertheless, continuous IT opiate infusion remains one of the most
effective methods of controlling cancer pain and affording patients,
maximal independence.
IT opioids are indicated for the management of cancer pain in two
circumstances: (1) in patients whose pain is refractory to reasonable doses
of oral opioids and (2) in patients who are unable to tolerate sufficient
doses of oral medications needed to adequately treat their pain due to
undesirable systemic side effects, mainly sedation. Although appropriate
management of the patient is the paramount goal, the current climate of
health care in the United States has dictated an ever increasing recognition
of the cost of care. In order to justify the cost of an implanted system,
potential candidates for pump implantation should have a life expectancy
of at least 3 to 6 months. Cost analysis studies comparing implanted
programmable pumps to external infusion systems have shown that for
patients requiring treatment more than 3 months, an IDDS is the more
cost-effective device.48,49
Continuous infusion of IT opiates has proven to be an effective and safe
method for controlling cancer pain.2,50–52 Adequate pain control that
results in significant reduction in oral narcotic intake and increase in
activity can be achieved in the majority of patients. A retrospective
multicenter survey regarding intraspinal opiate therapy revealed the

5009
average reduction in pain to be just over 60% (n = 382) regardless of
etiology.52 Increase in activity was noted in nearly 82% of patients (n =
399) with 59% realizing moderate to significant increases in activities of
daily living (ADL). Just over 95% of patients reported either good (42.9%)
or excellent (52.4%) pain relief. There were no significant differences in
the level of pain relief reported between patients with cancer and those
with nonmalignant pain syndromes. Complications related to the delivery
system occurred in 21.6% of patients (n = 380) and were most often
related to the catheter. Adverse drug effects were reported in
approximately one quarter of the patients. The most common adverse
effects were nausea and vomiting (25.2%) and pruritus (13.3%).
Perhaps the best evidence for the use of IDDS in patients with cancer
pain comes from the study of Smith et al.48 The authors performed a
randomized controlled trial of IDDS versus conventional medical
management (CMM) in a cohort of 202 patients. Entry criteria include
inadequately controlled pain of 5 or greater (0 to 10 VAS scale). Clinical
success was defined as either a 20% reduction in baseline VAS score or
equivalent VAS score accompanied by at least a 20% reduction in toxicity
following 4 full weeks of treatment. Nearly 85% (60 of 71) of patients
randomized to IDDS achieved clinical success compared to 70% (51 of
72) of patients who received CMM (P = .05). Mean pain scores fell from
7.8 to 3.7 (52%) for the IDDS group compared to 7.8 to 4.8 in the CMM
group (P = .055). Toxicity scores fell 50% for the IDDS group compared
with only 17% for the CMM group (P = .004). Interestingly, the IDDS also
showed improved survival, with 54% alive at 6 months compared with
37% in the CMM group.

INTRATHECAL DRUG DELIVERY FOR CHRONIC

NONCANCER PAIN
During the past two decades, there has been an increasing trend toward the
use of chronic IT opiates in the management of refractory noncancer pain
syndromes.6,8,52–60 Noncancer pain related to failed back surgery
syndrome is now the most common indication for the use of IDDS.
However, in spite of encouraging results in carefully selected patients with
noncancer-related pain, the use of intraspinal opiates for these chronic pain

5010
conditions has remained a controversial issue among clinicians, lay
persons, and government regulators. Indeed, much of the fear regarding
this issue has been born of the belief that the use of opioids in noncancer
pain invariably leads to tolerance and drug abuse. However, numerous
retrospective and prospective studies suggest that these previously held
beliefs may have been overly critical. Noncancer pain syndromes for
which IT opiates have been and might be used are outlined in Table 100.8.
The treatment strategy in patients with noncancer pain syndromes should
obey the principle that the least invasive and least costly interventions
should be attempted first, reserving more invasive and expensive therapies
for patients who fail the former. Unfortunately, patient selection for IT
administered opiates is not as straightforward as in patients with cancer.
Although there are ample reports of significant pain reduction using IDDS,
translation of pain reduction into functional improvement has been more
difficult to achieve.

TABLE 100.8 Chronic Pain States Currently Treated with Chronic

Spinal Drug Infusion
Cancer pain
Postlaminectomy syndrome
Nerve root injury
Adhesive spinal arachnoiditis
Brachial or lumbosacral plexitis
Complex regional pain syndrome
Type I (reflex sympathetic dystrophy)
Type II (causalgia)
Spinal cord injury pain
Phantom pain
Postherpetic neuralgia
Painful peripheral neuropathy
Poststroke pain
Intractable angina
HIV-related pain

Winkelmüller and Winkelmüller56 reported on 120 patients with

noncancer pain syndromes managed with long-term IT opiates with an
average follow-up of more than 3 years. Nearly three-quarters (74.2%) of
the patients derived benefit from the therapy, with a mean pain reduction
of 58%. Overall, 92% of patients were satisfied with the treatment and

5011
81% reported an improvement in their quality of life. The incidence of
tolerance was low, only 5.8% (seven patients) and was successfully
managed in four patients by means of “drug holidays.” Anderson and
Burchiel57 investigated the long-term efficacy and safety of IT morphine
in 33 patients with noncancer pain. These investigators noted a significant
reduction in pain which persisted up to 2 years. Although the daily IT of
morphine appeared to increase for the initial months of treatment, this
tended to stabilize and remain constant after 1 year.
Roberts et al.58 reported their results of IDDS for noncancer pain in 84
patients who were followed on average for 3 years. Nearly two-thirds of
their patients suffered from low back and/or radicular pain. Mean pain
reduction was around 60%, and 74% of patients self-reported increased
activity levels as well as significant reduction in oral medication. These
gains were not accompanied by change in work status. Technical
complications requiring an additional surgical procedure occurred in 40%
of patients. These patients were initially receiving relatively high doses of
morphine (9.95 mg per day) and by the end of 6 months, the mean daily
dose had escalated to 15.3 mg per day.
Finally, Deer et al.59 reported the results of IDDS for the treatment of
low back pain from the National Outcomes Registry for Low Back Pain.
Out of 166 patients enrolled to be trialed for an IDDS system, 136 (82%)
received a permanent implant. Scores for back and leg pain fell by an
average of 47% and 31% respectively at 12 months follow-up for those
who received an implant. In addition, more than 65% of patients
demonstrated reduction in Oswestry scores by at least one level compared
with baseline. At 1-year follow-up, 80% of patients indicated they were
“satisfied” with the therapy, and 87% said they would undergo the
procedure again for the same outcome.

Conclusion
IT drug delivery has evolved since its inception more than 30 years ago.
This technique represents a viable option for patients with intractable pain
conditions. Although once viewed solely as a salvage treatment, this is no
longer the case. The surgical procedure for IDDS placement is relatively

5012
simple, yet the management of patients with IDDS is has many associated
challenges. IDDS, particularly for patients with noncancer pain, represents
a long-term commitment on the part of both the patient and clinician.
Multiple problems will inevitably develop over the course of treatment,
including drug-related side effects and system complications that must be
addressed. Consequently, this therapy should be reserved for those who do
not respond to less invasive treatments. In spite of the potential problems
associated with this therapy, IDDS can be useful and beneficial to patients
who fail to respond to simpler pain treatments, so long as one adheres to
the principles of judicious patient selection, meticulous surgical technique,
and diligent patient management.

ACKNOWLEDGMENT
The authors would like to thank Richard K. Osenbach for his contributions
to the previous edition of this chapter.

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33. Malmberg AB, Yaksh TL. Pharmacology of the spinal action of ketorolac, morphine, ST-91,
U50488H, and L-PIA on the formalin test and an isobiologic analysis of the NSAID
interaction. Anesthesiology 1993;79:270–281.
34. Yu LC, Hansson P, Lundeberg T. The calcitonin gene-related peptide antagonist CGRP8-37
increases the latency to withdrawal responses in rats. Brain Res 1994;653:223–230.
35. Saulino M, Kim PS, Shaw E, et al. Practical considerations and patient selection for
intrathecal drug delivery in the management of chronic pain. J Pain Res 2014;7:627–638.
36. Hassenbusch SJ, Paice JA, Patt RB, et al. Clinical realities and economic considerations:
economics of intrathecal therapy. J Pain Symptom Manage 1997;14(3 suppl):S36–S48.
37. Kumar A, Maitra S, Khanna P, et al. Clonidine for management of chronic pain: a brief
review of the current evidences. Saudi J Anaesth 2014;8(1):92–96.
38. Fanciullo GJ, Rose RJ, Lunt PG, et al. The state of implantable pain therapies in the United
States: a nationwide survey of academic teaching programs. Anesth Analg 1999;88(6):1311–
1316.
39. Deer TR, Pope JE, Hayek SM, et al. The Polyanalgesic Consensus Conference (PACC):
Recommendations for intrathecal drug delivery: guidance for improving safety and mitigating
risks. Neuromodulation 2017;20:155–176. doi:10.1111/ner.12579.
40. Johnston J, Reich S, Baily A, et al. Shiley INFUSAID pump technology. Ann N Y Acad Sci
1988;531:57–65.
41. Synchromed Infusion System. Clinical Reference Guide for Pain Therapy. Minneapolis, MN:
Medtronic Neurological; 1998.
42. Follett KA, Burchiel KJ, Deer T, et al. Prevention of intrathecal drug delivery catheter-related
complications. Neuromodulation 2003;6:32–41.
43. Narang S, Srinivasan SK, Zinboonyahgoon N, et al. Upper antero-medial thigh as an
alternative site for implantation of intrathecal pumps: a case series. Neuromodulation
2016;19(6):655–663.
44. Coffey RJ, Divisions of Neuromodulation Clinical Research, Regulatory Vigilance, and
Biostatistics, Medtronic Inc, Minneapolis, MN. Mortality associated with implantation and
management of intrathecal opioid drug infusion systems to treat non-cancer pain:
identification, analysis and mitigation of risk factors. Oral presentation during the American
Society of Regional Anesthesia and Pain Medicine Annual Pain Meeting, Huntington Beach,
California, November 20, 2008.
45. Patt RB, Hassenbusch SJ. Implantable technology for pain control: identification and
management of problems and complications. In: Waldman SW, ed. Interventional Pain
Management. 2nd ed. Philadelphia, PA: WB Saunders; 2001:654–670.
46. Cole BE. Neuroendocrine implications of opioids therapy. Curr Pain Headache Rep
2007;11:89–92.
47. Deer T, Krames ES, Hassenbusch SJ, et al. Management of intrathecal cathetertip
inflammatory masses: an updated 2007 consensus statement from an expert panel.
Neuromodulation 2008;11:77–91.
48. Smith TJ, Staats PS, Deer T, et al. Randomized clinical trial of an implantable drug delivery
system compared with comprehensive medical management for refractory cancer pain: impact
on pain, drug-related toxicity, and survival. J Clin Oncol 2002;20(19):4040–4049.
49. Bedder MD, Burchiel KJ, Larson A. Cost analysis of two implantable narcotic delivery
systems. J Pain Symptom Management 1991;6:368–373.

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50. Krames ES, Gershow J, Glassberg A, et al. Continuous infusion of spinally administered
narcotics for the relief of pain due to malignant disorders. Cancer 1985;56:696–702.
51. Onofrio BM, Yaksh TL. Long-term pain relief produced by intrathecal morphine infusion in
53 patients. J Neurosurg 1990;72:200–209.
52. Paice JA, Penn RD, Shott S. Intraspinal morphine for chronic pain: a retrospective,
multicenter study. J Pain Symptom Manage 1996;11(2):71–80.
53. Krames ES. Intrathecal infusional therapies for intractable pain: patient management
guidelines. J Pain Symptom Manage 1993;8:36–46.
54. Krames ES. Intraspinal opioid therapy for chronic nonmalignant pain: current practice and
clinical guidelines. J Pain Symptom Manage 1996;11:333–352.
55. Tutak U, Doleys DM. Intrathecal infusion systems for treatment of chronic low back and leg
pain of noncancer origin. South Med J 1996;89:295–300.
56. Winkelmüller M, Winkelmüller W. Long-term effects of continuous intrathecal opioid
treatment in chronic pain of nonmalignant etiology. J Neurosurg 1996;85:458–467.
57. Anderson A, Burchiel KJ. A prospective study of long-term intrathecal morphine in the
treatment of nonmalignant pain. Neurosurgery 1999;44:289–301.
58. Roberts LJ, Finch PM, Goucke CR, et al. Outcome of intrathecal opioids in chronic non-
cancer pain. Eur J Pain 2001;5:353–361.
59. Deer T, Chapple I, Classen A, et al. Intrathecal drug delivery for treatment of chronic low
back pain: report from the National Outcomes Registry for Low Back Pain. Pain Med
2004;5:6–13.
60. Turner JA, Sears JM, Loeser J. Programmable intrathecal opioid delivery systems for chronic
non-cancer pain: a systematic review of effectiveness and complications. Clin J Pain
2007;23:180–195.

5016
CHAPTER 101
Intradiscal Therapies for Low
Back Pain
YAKOV VOROBEYCHIK and NIKOLAI BOGDUK

Intradiscal therapies are interventions in which agents—physical or

chemical—are delivered into an intervertebral disk, either to stop pain or
to reverse or remove processes responsible for the pain. Fundamental to
the use of such interventions is the belief that the lumbar intervertebral
disks are a common source of chronic low back pain. This belief has a
long history and is based on a variety of circumstantial and direct
evidence.

Discogenic Pain
The proposition that lumbar disks could be a source of back pain has been
espoused at least since as long ago as 1940.1 Over the ensuing years,
opponents have raised various arguments against the concept. However,
each of these arguments has been systematically refuted.1
Originally, the argument was that disks could not hurt because they
lacked a nerve supply. This argument was maintained as recently as
19802,3 despite the fact that studies published in 19404 and 19595 had
shown that the lumbar disks were, indeed, innervated. Studies in 19806 and
19817 confirmed that innervation and established its source. Later studies,
using modern techniques, confirmed the presence of nociceptive nerves in
the outer third of the anulus fibrosus of normal disks.8–11 Other studies
showed that, in addition to their normal innervation, damaged or
degenerated disks can attract an ingrowth of new nerves, which follow
blood vessels and granulation tissue.12–14
The second argument was that, although disks might be innervated, they
did not hurt (the innervation being vasomotor or serving some function

5017
other than nociception). This was refuted by observations that back pain
could be provoked by noxious stimulation of disks. When discography was
developed as a diagnostic test for disk herniation, investigators noted that
injections of contrast medium into affected disks reproduced the patients’
low back pain.15–18 Others, when operating on patients under local
anesthesia, observed that probing the disk evoked back pain.19,20 A
modern study found that, of all the structures in the lumbar spine
submitted to mechanical provocation, the disks were the most potent
source of back pain.21
The third argument was that, although disks might hurt, there are no
means of diagnosing the condition. This argument is correct if the
diagnostic test relies on detecting degenerative changes on imaging of the
disk. So-called degenerative changes are almost as prevalent in patients
with back pain as in asymptomatic subjects and have no clinically
significant, statistical association with pain.22 For this reason, those who
pursue discogenic pain rely on disk stimulation as the diagnostic test.
Disk stimulation is an adaptation of discography.23 Discography was
originally developed in order to demonstrate the internal morphology of
the disk, but this is largely irrelevant to diagnosis. Disk stimulation differs
in that its emphasis is on the patient’s response to stimulation of the disk
with injections of contrast medium or normal saline. Morphologic changes
are of secondary importance.
The operational guidelines for disk stimulation23 are that for a disk to be
deemed to be the source of pain:
• Stimulating the disk must reproduce the patient’s pain (known as a
concordant response).
• Stimulation of adjacent disks does not reproduce pain.
• Pain is evoked at low thresholds of stimulation: less than 20 psi (0.14
kPa).
• The evoked pain is clinically significant, that is, rated as greater than
7 out of 10 on a numerical pain rating scale or its equivalent.
These guidelines were developed on the basis of various studies that
were performed in order to ensure consistency of practice and
interpretation and to minimize false-positive rates caused by excessive
stimulation or by hyperalgesia.1

5018
 The validity of disk stimulation was challenged by studies that reported
purportedly high false-positive rates.24 However, when the data of those
studies were analyzed according to operational guidelines, the false-
positive rates all but disappeared.1 A systematic review showed that the
false-positive rate of disk stimulation was less than 10% and probably
closer to 6%,25 which is a tolerably low rate.
The final argument against lumbar discogenic pain has been that there is
no pathology that renders the disk painful. This has now been
comprehensively refuted,1 as shown in the following section.

Pathology
It is now evident that the lumbar disk responds to a variety of nutritional,
metabolic, and mechanical insults in a similar manner.26,27 Those
responses are expressed as what, to date, have been called degenerative
changes.
The disk matrix is produced by chondrocytes in the nucleus pulposus,
and synthesis is promoted by factors such as transforming growth factor
(TGF) and insulin-like growth factor (IGF), which reside in the matrix
(Fig. 101.1). Under normal conditions, the matrix is continually renewed.
For this to occur, old matrix has to be degraded. The chondrocyte produces
enzymes—known as matrix metalloproteinases (MMPs), which degrade
the matrix. These enzymes are controlled by tissue inhibitors of matrix
metalloproteinases (TIMMPs).26,27

5019
FIGURE 101.1 The molecular biology of disk degeneration and internal disk disruption. Bold
arrows and plus signs (+) indicate production, promotion, or stimulation. Dashed arrows indicate
attraction. Dotted arrows and minus signs (−) indicate inhibitory influences. Open arrows and
asterisks (*) indicate degradative effects. Chondro, chondrocyte; IFN, interferon; IGF, insulin-like
growth factor; IL, interleukins; LTs, leukotrienes; NOS, nitric oxide synthetase; NO3, peroxynitrite;
NO, nitric oxide; O2−, hyperoxide; PGs, prostaglandins; PLA2, phospholipase A2; Macro,
macrophage; MMPs, matrix metalloproteinases; TFG, transforming growth factor; TIMMPs, tissue
inhibitors of MMPs; TNFα, tumor necrosis factor alpha.

Injury disturbs the normal balance between synthesis and degradation

toward degradation26,27 (see Fig. 101.1). Injury results in the liberation of
phospholipases (PLAs), which in turn act on arachidonic acid to produce
prostaglandins (PGs) and leukotrienes (LTs). LTs are chemotactic and
attract macrophages. Macrophages release superoxide and cytokines such
as tumor necrosis factor alpha (TNFα), interleukins (IL), and interferon
(IFN). These cytokines stimulate the chondrocyte to produce more MMPs
and, thereby, promote matrix degradation. The cytokines also stimulate
nitric oxide synthetase to produce nitric oxide (NO). NO not only inhibits
the chondrocyte but also combines with superoxide to produce
peroxynitrite, which inhibits the tissue inhibitors of MMPs, thereby
promoting matrix degradation. Superoxide itself inhibits the chondrocyte
and directly degrades the matrix.

5020
 As the nucleus degrades, it is no longer able to retain water and loses its
hydrostatic properties. Pressures within the nucleus become irregular and
reduced28,29 (Fig. 101.2), and the nucleus is less able to sustain
compression loads. Meanwhile, compression loads are increasingly borne
by the posterior anulus, which is subjected to loads substantially above
normal28,29 (see Fig. 101.2). Irregular pressures in the nucleus and
increased stresses in the posterior anulus are each independently associated
with the disk being painful.30

FIGURE 101.2 The internal stress profile across a diameter of an injured intervertebral disk.
Stresses are normal in the anterior anulus, decreased and irregular across the nucleus, and raised in
the posterior anulus.

The depressurized nucleus is unable to brace the anulus internally. As a

result, the inner anulus buckles and delaminates. Progressive disruption of
the anulus leads to the development of radial fissures, which are
characteristic of the condition known as internal disk disruption.31–33 The
severity of disruption can be graded according to the extent to which
fissures penetrate the anulus (Fig. 101.3). Grade III fissures reach the outer
third of the anulus and become grade IV fissures if they extend
circumferentially around the outer anulus. These fissures are the hallmark
of internal disk disruption. They do not represent age changes34 and are
most likely features of previous injury. Grade III or grade IV fissures are
imperfectly but nonetheless significantly associated with the disk being
painful on disk stimulation.1,34–39

5021
FIGURE 101.3 The grading of radial fissures in internal disk disruption.

Experimental studies have now produced internal disk disruption in

laboratory animals.40,41 The initiating injury was fracture of the vertebral
endplate. This injury precipitates the biochemical and morphologic
changes of internal disk disruption. Biomechanics studies in cadavers have
shown that endplate fractures can be precipitated by fatigue failure.28
Immediately after fracture of the endplate, the disk expresses the
biophysical features of internal disk disruption.28 Endplate fractures are
caused by repeated compression loading and can occur after as few as 100
cycles of compression at 50% to 80% of ultimate tensile strength of the
endplate.42,43 This level of stress is well within the range experienced
during normal occupational heavy lifting.
Internal disk disruption can be diagnosed in patients. Radial and
circumferential fissures can be demonstrated by computed tomography
(CT) discography, in which a CT scan is obtained after contrast medium
has been injected into the disk (Fig. 101.4). Demonstrating such fissures
converts the diagnosis from discogenic pain to painful internal disk
disruption. Otherwise, certain features evident on magnetic resonance
imaging (MRI) are consistent with features of internal disk disruption.

5022
FIGURE 101.4 Postdiscography computed tomography scans showing Grade 0 and a Grade IV
internal disk disruption. In the Grade 0 disk, the contrast medium is contained in the nucleus
pulposus, with a regular, smooth perimeter. In the Grade IV disk, a Grade III radial fissure has
penetrated the anulus fibrosus and has spread circumferentially to become a Grade IV fissure.
(Images kindly provided by Dr. Milton Landers, Wichita, Kansas.)

High-intensity zones (HIZ) in the posterior anulus (Fig. 101.5) represent

the cross-sectional appearance of a circumferential fissure. They occur in
20% to 30% of patients with chronic low back pain and correlate with the
affected disk being painful. Although figures differ between studies (Table
101.1), the pooled data show that an HIZ has a positive likelihood ratio
greater than 3 for the affected disk being the source of pain.

5023
FIGURE 101.5 A T2-weighted, midline, sagittal magnetic resonance scan showing a high-
intensity zone (arrow) in the anulus fibrosus of the L4–L5 disk. (Image kindly provided by Dr.
Milton Landers, Wichita, Kansas.)

TABLE 101.1 The Sensitivity, Specificity, and Likelihood Ratio of

the High-intensity Zone as a Predictor of the Affected Disc being
Painful, as Reported by 12 Studies
Likelihood
Sample Size Sensitivity Specificity Ratio 95% CI Source
142 0.37 1.00 ∞ — Peng et al.44
120 0.82 0.89 7.5 4.0–14.1 Aprill et al.36
256 0.45 0.94 7.5 3.7–15.1 Chen et al.45
152 0.27 0.95 5.4 1.7–17.1 Saifuddin et
al.46
101 0.52 0.90 5.2 2.4–11.2 Ito et al.47
155 0.81 0.79 3.9 2.5–6.0 Lam et al.48
178 0.57 0.84 3.6 2.2–5.7 Kang et al.49
109 0.45 0.84 2.8 1.4–5.5 Carragee et
al.50
152 0.26 0.90 2.6 1.2–5.8 Kokkonen et
al.39
97 0.56 0.70 1.9 1.2–3.0 Lim et al.38
116 0.27 0.85 1.8 0.9–3.8 Weishaupt et

5024
 al.51
80 0.09 0.93 1.3 0.3–5.4 Ricketson et
al.52
1,658 0.45 0.88 3.8 3.1–4.5 ALL
95% CI, 95% confidence interval, the prevalence represents the number of disks studied that
showed the sign.

Modic lesions occur in the spongiosa of the vertebral body above an

abnormal disk (Fig. 101.6). Type 1 lesions appear dark on T1-weighted
images but bright on T2-weighted images and represent bone marrow
edema. Type 2 lesions appear bright both on T1-weighted images and T2-
weighted images and represent fat deposition (implicitly
postinflammatory). They occur in about 33% of patients with chronic back
pain and correlate significantly with the affected disk being painful, the
pooled data indicating a positive likelihood ratio of about 3 (Table 101.2).

FIGURE 101.6 Sagittal magnetic resonance scans showing the appearance of type 1 and type 2
Modic lesions on T1-weighted and T2-weighted scans. (Images kindly provided by Dr. Tim Maus,
Mayo Clinic, Rochester, Minnesota.)

5025
 TABLE 101.2 The Sensitivity, Specificity, and Likelihood Ratio of
Modic Changes as Predictors of the Affected Disc being Painful, as
Reported by 12 Studies
Likelihood
Sample Sensitivity Specificity Ratio 95% CI Source
2,457 0.25 0.94 4.2 3.3–5.2 Thompson et
al.53
152 0.23 0.97 7.7 1.9–31.6 Braithwaite et
al.54
101 0.22 0.95 4.4 1.3–15.0 Ito et al.47
255 0.18 0.90 1.8 0.9–3.5 Sandhu et al.55
178 0.14 0.87 1.1 0.5–2.6 Kang et al.49
97 0.09 0.83 0.52 0.2–1.8 Lim et al.38
3,240 0.24 0.83 3.4 2.8–4.1 ALL
95% CI, 95% confidence interval of likelihood ratio, the prevalence represents the number of disks
studied that showed the sign.

In patients with chronic low back pain, the prevalence of internal disk
disruption is about least 40%.56,57 The diagnostic features are reproduction
of the patient’s pain by disk stimulation and demonstration of a radial
fissure on postdiscography CT scan.1
The mechanism of pain in internal disk disruption appears to be a
combination of mechanical and chemical factors. The increased pressures
in the posterior anulus provide a basis for mechanical pain. The inordinate
pressures in the posterior anulus would stimulate the nociceptive nerve
endings in the outer anulus. Inflammatory mediators from the degraded
nucleus provide a basis for chemical pain. Mediators that track through the
radial fissure would reach the nerve endings in the outer anulus. They
could stimulate the nerve endings to produce chemical nociception or they
could sensitize the endings and lower their threshold to mechanical
stimulation. Both mechanisms could be amplified if new nerve fibers are
attracted into the disk by the radial fissure.12–14

Therapies
The recognition of lumbar discogenic pain and internal disk disruption has
attracted the exploration of a number of therapies that specifically target

5026
this condition. Variously they involve ablating the nerves that mediate the
pain, injecting drugs or chemicals to suppress chemical nociception, or
injecting agents intended to reverse the degradative processes within the
disk.

ABLATION
Attempts have been made to denervate painful disks at a variety of sites,
using a variety of means. Most have proved unsuccessful.

Ramus Communicans Lesions

A prospective, controlled study compared the effects of thermal
radiofrequency lesioning in the region of the ramus communicans with
those of injections of lidocaine over the same site.58 Statistically,
significant differences arose in favor of radiofrequency treatment, at 4
months following intervention. However, the degree of relief afforded by
radiofrequency therapy was modest, amounting to only a 46% mean
decrease in pain, and the authors did not report the number of patients
experiencing high-grade relief (75% to 100%). Moreover, the study was
confounded because patients who received radiofrequency therapy also
received an injection of triamcinolone (40 mg) at the site treated, which
the control group did not receive. It is, therefore, not evident if the modest
improvements seen in the study group arose from the radiofrequency
lesion created, or the injection of corticosteroids.

Intranuclear Radiofrequency
The nucleus pulposus is normally devoid of nerve endings. Therefore,
placing radiofrequency lesions in the nucleus has no prospect of
coagulating nerves in the immediate vicinity of the electrode. However,
proponents of intranuclear radiofrequency argued that the electric field
produced around the electrode would be sufficient to heat and destroy
nerve fibers in the outer anulus fibrosus, and thereby provide relief of
pain59; but cadaver studies have dispelled this notion.60,61 Significant
heating does not occur in the outer anulus. A controlled trial demonstrated
that intranuclear radiofrequency achieved no greater relief of pain than
sham therapy.62 What were promoted as successful outcomes in earlier

5027
observational studies amounted to no more than placebo responses.

PERCUTANEOUS INTRADISCAL RADIOFREQUENCY

THERMOCOAGULATION
Percutaneous intradiscal radiofrequency thermocoagulation (PIRFT)
involves inserting a flexible radiofrequency electrode into the posterior
anulus fibrosus in order to coagulate fissures and nociceptors with a heat
lesion.63 Good results were reported in a pilot study, with some 40% of
patients achieving at least 50% relief of pain, coupled with improvement in
disability.63 However, a controlled trial later found minimal improvements
in pain and no differences in outcome between active and sham
treatment.64

Intradiscal Electrothermal Therapy

Intradiscal electrothermal therapy (IDET) was a treatment developed in the
mid-1990s that involved threading a flexible heating element into the
posterior anulus fibrosus or along the nucleus–anulus boundary in order to
ablate nociceptors in the posterior anulus and to seal fissures.65–69 The
procedure attracted attention in the form of observational and controlled
studies.69–74
In observational studies, the proportion of patients who achieved greater
than 50% relief ranged from 50%75–77 to 70%,78,79 and up to 20% of
patients achieved complete relief.75,76 In some studies, outcomes were
maintained for 2 years.76,80,81
Two randomized, placebo-controlled trials had different results.82,83 In
one trial, a clear difference was demonstrated between placebo and
experimental groups, although success rates were modest.82 Greater than
50% relief was achieved in 40% of patients, among whom 22%
experienced 75% to 100% relief of pain. These outcomes were consonant
with those reported from observational studies. The other controlled
study83 found no effect, either from active treatment or from sham
treatment. This lack of any response is dissonant with the outcomes of
observational studies, and the lack of any placebo effect is curious and
unexplained. However, because no placebo effects were demonstrated, this
study does not provide evidence that the responses in other studies were

5028
due to placebo effects.
Despite these data, the popularity of IDET has all but evaporated. To
some extent, that could be because successful outcomes occurred in only a
modest proportion of patients or because many patients suffer exacerbation
of the pain rather than relief. The principal factor, however, seems to be
the failure of the procedure to attract reimbursement in the US health
system.

L’DISQ
L’DISQ is the proprietary name for a flexible and navigable electrode that
can be used to deliver thermal lesions into an anulus fibrosus. It differs
from its predecessors in that the tip of the electrode can be bent by an
internal mechanical device in order to change its course as it is pushed
across the anulus. A single case series reported that 11 of 20 patients
treated with this device achieved 50% relief of pain at 24 weeks and 48
weeks after treatment.84 From the data published, it is not clear the extent
to which these same patients reduced their disability or improved their
function.

Coblation
Coblation is a procedure that uses an electrode bathed in saline that
produces a so-called “plasma field” around the tip of the electrode
consisting of ionized particles. The electrode can be used to dissolve and
remove (“coblate”) tissues. When used for discogenic pain, the electrode is
inserted into the outer anulus fibrosus ostensibly to remove material in
radial fissures. One study reported that 10 of 17 patients so treated
achieved at least 50% reduction in pain,85 but no outcome data were
reported on restoration of function or continuing health care.

Biacuplasty
Intradiscal biacuplasty is a procedure in which cooled, radiofrequency
electrodes are inserted into opposite, posterolateral corners of the anulus
fibrosus of the target disk (Fig. 101.7). The rationale for the procedure is
that arcing a heat lesion between the electrodes will ablate nociceptors in
the posterior anulus or around fissures traversing the anulus. This

5029
procedure has received sustained attention from one particular group.

FIGURE 101.7 Fluoroscopy images of electrodes placed for intradiscal biacuplasty. A:

Anteroposterior view. B: Lateral view. C: Declined view, with the x-ray beam passing to view the
L4–L5 disk from behind and below. D: Declined view on which the posterior margin of the disk
has been drawn as a dotted line, in order to show how the electrodes are inserted radially across the
posterolateral corners of the anulus fibrosus. (Reproduced with permission from International
Spinal Intervention Society. Lumbar disc access: Appendix 2: Transdiscal Biacuplasty. In: Bogduk
N, ed. Practice Guidelines for Spinal Diagnostic and Treatment Procedures. 2nd ed. San Francisco,
CA: International Spine Intervention Society; 2013:417–419.)

A pilot study of 15 patients reported that 6 had greater than 50% relief
of pain at 6 months, coupled with improvement in physical function.86 A
subsequent letter reported that 7 patients had this same response at 12
months.87 In a randomized study, biacuplasty was shown to be more
effective than sham therapy,88 but success rates were modest. With success
being defined as a reduction of pain by 2 points out of 10 and
improvement in physical function by 15 points out of 100, 8 of 27 patients
(30%) achieved a successful outcome after biacuplasty compared with

5030
only 1 of 30 after sham treatment. At 12 months follow-up of 22 patients,
group scores for pain and physical function continued to improve, but only
4 patients (18% of those followed, or 15% of those originally treated)
satisfied the criteria for successful outcome.89
Similar, modest outcomes have been reported by others. In one study, 8
of 15 patients had 50% relief of pain or better.90 In another study, 4 of 14
patients had greater than 60% relief at 6 months, sustained for 12 months,
with 1 having complete relief over this period.91
Although the outcomes of biacuplasty appear to be modest, they can be
viewed in the context of alternatives for patients with discogenic pain. A
randomized controlled study showed that, despite modest success rates,
biacuplasty coupled with conventional medical management was clearly
superior to conventional medical management alone, in terms of group
scores for pain and function.92,93 Some 42% of patients treated with
biacuplasty had at least 50% relief of pain at 6 months, compared with
only 7% treated by conventional medical management.92 This outcome
was largely sustained at 12 months.93 Furthermore, the group scores for
relief of pain and improvement in function were not appreciably different
from those for surgery for the same condition.93
Taken in context, the outcomes of biacuplasty make it an entertainable
option for patients with discogenic pain. It is a remarkably safe procedure
that is easy to perform and tolerated by patients. No alternatives have
proven to offer better prospects of relief. A technical issue limits the
efficacy of biacuplasty. The iliac crests can prevent optimal placement of
electrodes into L5–S1 disks, such that not all of the posterior anulus can be
adequately encompassed by the thermal lesion delivered. If this can be
overcome, success rates might be improved.

CHEMICAL THERAPIES
Various chemicals have been used for discogenic pain. For some, there is a
reasonable rationale because the drug administered targets one or other of
the agents involved in disk degradation. For others, a solid rationale is
lacking.

Intradiscal Steroids

5031
Because phospholipase A2 (PLA2) has been implicated in disk
degeneration and disk injury, intradiscal injection of corticosteroids has a
rationale. By inhibiting PLA2, steroids prevent the arachidonic acid
cascade and the production of PGs and LTs (see Fig. 101.1).
In early studies, investigators claimed good results when they used
intradiscal steroids to treat patients with a variety of complaints described
as back pain and/or sciatic but without a diagnosis of discogenic pain
having been made objectively.94–97 In later studies, a diagnosis of
discogenic pain was established by discography, and therapeutic injections
were performed at the time of discography.98–100
Two controlled trials have refuted any attributable effect from
intradiscal steroids for discogenic pain diagnosed solely by disk
stimulation. The first compared the therapeutic effects of intradiscal
methylprednisolone (80 mg) with those of 1.5 mL intradiscal bupivacaine
(0.5%).98 At 10 to 14 days after treatment, improvements in pain and
disability occurred in similar, small proportions of patients in both groups.
In the second trial, responses to intradiscal injections of either 40-mg
methylprednisolone or 1-mL normal saline were compared. At 1-year
follow-up, there were no discernible improvements in disability or pain
scores in either group.99
A different picture has emerged for the treatment of painful disks that
exhibit Modic changes. In one study at 1 month after intradiscal injection
of 25 mg prednisolone, 1 of 11 patients with type 2 lesions reported greater
than 50% relief of pain, whereas 18 of 33 patients with type 1 lesions and
13 of 25 patients with combined lesions reported that degree of relief.101
Another study found significant improvements in pain 1 day after
intradiscal injection of steroids in patients with type 1 lesions,102 but
improvements attenuated over 12 months or longer follow-up. However, a
controlled trial has provided support for intradiscal steroids in such
patients.
Patients with Modic type 1 or Modic type 2 lesions were randomized to
receive intradiscal injections of saline, betamethasone, or betamethasone
mixed with a Chinese medicine extract.103 No significant improvements
occurred in patients treated with normal saline, but at 3 and 6 months,
significant improvements in pain scores and in disability occurred in all

5032
groups treated with betamethasone, with or without extract, and regardless
of lesions being type 1 or type 2. In those groups, no significant
differences arose according to type of treatment or type of Modic lesion.
At 6 months, mean pain scores dropped from 7 to 2, and disability scores
dropped from 35 to 15. However, the authors did not report the success
rates for any given definition of success.
Had there been no placebo-controlled trial, the observational studies of
intradiscal steroids for Modic lesions could be dismissed as showing no
more than placebo responses. However, there being a positive, placebo-
controlled trial, the treatment cannot be summarily dismissed as a placebo.
What is still required, however, is evidence that this treatment obviates
need for other health care and evidence either that it has long-term effects
or can be repeated safely in order to reinstate relief if it wanes.

Etanercept
Because TNFα is involved in the degradation of lumbar disks (see Fig.
101.1), there is a rationale for using TNF-blocking agents to treat
discogenic pain. One such agent is etanercept, which binds TNF receptors.
A placebo-controlled study assessed the efficacy of intradiscal injection
of etanercept in doses increasing from 0.1 to 1.5 mg.104 No differences
were found at 1 month, either within or between patients treated with
etanercept or normal saline, with respect to relief of pain or disability. A
second controlled trial compared the effects of 10 mg etanercept plus
bupivacaine with those of bupivacaine alone.105 At 4 weeks after
treatment, improvements in pain scores and disability were significantly
greater in the etanercept group. Moreover, 56% of patients treated with
etanercept achieved at least 50% relief of pain, compared with only 23%
of those treated with bupivacaine alone. However, at 8 weeks, the
therapeutic benefits had extinguished.
Thus, there is evidence that a high dose of etanercept has therapeutic
effects beyond those of placebo, but those effects occur only in some
patients and are not lasting. By inference, it seems that etanercept can
block the inflammatory processes of internal disk disruption, but a single
dose is not enough to overcome continued production of TNFα.

5033
Methylene Blue
Methylene blue has weak neurolytic effects and inhibits guanylate cyclase
and nitric oxide synthesis. The latter property affords it a role in the
treatment of discogenic pain by blocking the degradative effects of NO
(see Fig. 101.1).
In a pilot study, a team of investigators in China reported astounding
results from the use of intradiscal methylene blue for discogenic back
pain.106 They subsequently published a sham-controlled trial that
corroborated these results. At 24 months, 19% of the patients treated with
methylene blue had complete relief of pain and no restriction in activities;
a further 72% had only slight pain and mild restriction of activities.107 Of
the sham control group, only 15% had slight pain; the remainder had
continuing pain. Later, another study from China echoed these results but
published only group data that showed improvements in pain scores and
disability.108
These results have not been reproduced in open-label studies by others.
One study had only 1 patient out of 8 who obtained complete relief of
pain, which continued for 12 months; the other 7 patients had no relief or
various grades of relief that lasted no longer than 6 months.109 A second
study reported success rates based on 2 points reduction of pain but did not
report the proportions of patients achieving 50% relief or complete
relief.110 A third study provided 50% relief to 5 of 15 patients.111 A fourth
study had 3 of 16 patients achieve 50% relief or greater at 2 months,
dwindling to 1 of 16 patients at 6 months.112
Observational studies are considered a low level of evidence when
results are positive, but when results are negative, such studies constitute
strong evidence. In the process of scientific enquiry, reproduction of
results is essential for credibility. The failure to match the results of the
original studies from China is enigmatic, if not curious.

Antibiotics
A group of investigators explored the conjecture that back pain in patients
with Modic lesions was due to infection of the disk by anaerobic
organisms. On this assumption, they conducted a pilot study, followed by a
placebo-controlled trial of antibiotic therapy for back pain in patients with

5034
disk herniations and Modic lesions affecting the same level.113 Their group
data showed significantly greater improvements in pain and disability in
those patients treated with antibiotics. Despite these results, however,
some 67% of their patients still had pain at 1 year. Although heralded as a
major breakthrough in the treatment of back pain, this study has attracted
criticism on several counts.114,115 A later study, using ribosomal assays of
herniated disk material, found no evidence of bacterial infection.116

Proliferants
Some investigators have sought to ameliorate disk pain through the
injection of substances purported to enhance healing of diseased disk
tissue. Typically, solutions have been used that contain chondroitin sulfate,
glucosamine hydrochloride, dimethyl sulfoxide (DMSO), bupivacaine, and
hypertonic dextrose117,118 or hypertonic dextrose alone.119
The literature on using these agents is limited to isolated publications
that claimed good outcomes but which provided little objective data.
Although they reported various degrees of relief of pain, for various
durations, none provided data on function or subsequent use of other
health care. So, it is not evident from the literature if these interventions
make any impact on the burden of illness.
Although authors have referred to injection of these agents as
“regenerative” or “proliferative” therapies, chondroitin and glucosamine
have not been shown to have any specific anabolic effect on the disk, and
DMSO is neurolytic rather than restorative. The term regenerative seems
more appropriate for emerging intradiscal therapies that have a known
positive effect on connective tissue metabolism.

BIOLOGICS
The term biologics is used to refer to elements, naturally found in blood or
bone marrow as cells or proteins, that are known from studies in vitro and
in laboratory animals to promote healing of connective tissues or to inhibit
cytokines or degradative enzymes. Jointly or severally, such elements have
been used extensively to treat musculoskeletal disorders such as tendon
injuries and osteoarthritis. Based on their reputed success in these
conditions, they have been explored for the treatment of discogenic pain.

5035
Sealant
A proprietary preparation of fibrinogen, referred to as a sealant, has been
used to control bleeding in neurosurgery, but it also inhibits cytokines and
MMPs. These properties made it an attractive agent ostensibly to seal
radial fissures and inhibit the degradative processes of internal disk
disruption. A pilot study of intradiscal injection of sealant in 15 patients
provided 7 patients with greater than 50% relief of pain, accompanied with
improvements in disability, at 1 year after treatment, with 6 maintaining
this response to 2 years.120

Platelet-Rich Plasma
Platelet-rich plasma (PRP) contains high concentrations of TGF, IGF,
basic fibroblast growth factor, and platelet-derived growth factor, which
promote matrix synthesis (see Fig. 101.1) and connective tissue healing.121
It has, therefore, been used in attempts to produce these responses in
internal disk disruption.
The first study compared the effects of intradiscal PRP with those of a
control injection of contrast medium.122 Statistically significant
differences in favor of PRP were found in some outcome measures,
although not for “current pain” or physical function. Success rates of
treatment were not reported. An open-label study provided 9 out of 22
patients with greater than 50% relief of pain, coupled with greater than
30% improvement in disability, at 6 months after treatment.123

α2 Macroglobulin
Fibronectin-aggrecan complex (FAC) is a marker of cartilage degradation.
Its formation is inhibited by α2 macroglobulin (A2M). A study explored
the effects of intradiscal injection of plasma rich in A2M in 24 patients in
whom disk lavage detected FAC or not.124 At 6 months after treatment,
significantly greater improvements in pain and in disability were found in
those patients who were FAC positive.

Stem Cells
Of all the biologics, intradiscal stem cell therapy has attracted the greatest
amount of attention. There is an abundant literature on the effects of stem

5036
cells on disk tissue in vitro and in laboratory animals.125–127 In these
models, stem cells suppress genes for synthesis of degradative enzymes,
increase proteoglycan content and extracellular matrix, improve the
histologic appearance of the disk, increase disk height, and improve MRI
appearance.125–127 Several small studies have established the feasibility
and safety of intradiscal injection of stem cells in humans.125
With respect to effectiveness, an observational study found that 16 of 26
patients achieved greater than 50% relief of pain at 12 months after
intradiscal stem cells, with 2 of these patients being completely pain free.
Relief was accompanied by improvements in disability.128 These outcomes
were largely sustained at 2 years.129
An earlier study compared the outcomes from intradiscal stem cells with
those of sham therapy.130 It claimed that stem cell therapy was effective on
the grounds that patients had greater and more sustained relief of pain after
treatment with intradiscal stem cells. However, pain scores and disability
scores were not compared statistically between groups. Inspection of the
published data suggests that stem cell therapy reduced the mean values of
pain scores to levels slightly lower than those achieved by sham therapy at
6 months after treatment but not at 3 or 12 months. Furthermore, although
5 of 12 treated patients had good relief of pain, so did 4 of 12 control
patients. The authors were concerned that active treatment appeared to
work in only 40% of patients and were not able to explain this
phenomenon.
A leading possibility stems from the fact that all of the preliminary and
subsequent studies of intradiscal injection of stem cells selected patients on
the basis of MRI features of disk degeneration, but disk degeneration
occurs commonly in asymptomatic subjects and has no clinically
significant association with the affected disk being painful.22 Therefore,
the disks that were treated may not have been the source of pain in many
of the patients treated. The prospect arises that the success rates of
intradiscal stem cell therapy might be substantially improved if the
treatment was applied to disks shown to be painful by disk stimulation or
likely to be painful on the basis of Modic changes or HIZs on MRI.

Discussion
5037
A common theme in most of the studies of treatments for discogenic pain
is that many investigators seem intent on discovering a cure for discogenic
pain. Some have affiliations with or proprietary interests in the device,
technique, or agent that they have investigated or promoted.
Another theme is “50% relief in 50% of patients.” This seems to be
offered as sufficient evidence that the treatment is successful. However,
what is missing from the literature is any evidence that such outcomes
actually reduce the burden of illness: that patients return to normal
function or near normal but satisfying function and require no continuing
health care for their back pain.
These themes create points of resistance among consumers of research
data. Tutored consumers would be wary of reporting bias and generous
definitions of success. Developments in this field would be more
compelling if and once independent, third parties conducted replication
studies to determine how well a new treatment works, for how long, and in
which types of patients.
A parallel theme is the hope that ablating parts of a disk, or injecting
something into it, will be enough to produce a cure. This overlooks the fact
that disrupted disks continue to be subject to offending compression loads
during normal activities of daily living. Biomechanics continues to drive
degradative processes and threatens to overwhelm the effects of single-
shot interventions. Thus, although thermal interventions might temporarily
ablate fissures and degrade cytokines, continued compression threatens to
create new fissures and cytokines. Thermal interventions might destroy
nociceptors, but they will likely regenerate. Chemicals might inhibit agents
currently active in the disk, but the dose will not be enough to antagonize
newly secreted agents. Biologics might promote synthesis of new matrix,
but will they be strong enough to overcome continued degradation? In that
regard, what is seen in a Petri dish is not what happens in vivo. Cells that
benefit from biologics in a Petri dish are not constantly subjected to
offensive compression loads. These considerations warn that the current
battery of interventions for discogenic pain might have partial or
temporary effects, but none are designed to stop permanently the
biochemical and morphologic responses to biomechanical injury.

5038
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96. Graham CE. Chemonucleolysis: a double blind study comparing chemonucleolysis with intra
discal hydrocortisone: in the treatment of backache and sciatica. Clin Orthop Relat Res
1976;117:179–192.
97. Wilkinson HA, Schuman N. Intradiscal corticosteroids in the treatment of lumbar and cervical
disc problems. Spine 1980;5:385–389.
98. Simmons JW, McMillin JN, Emery SF, et al. Intradiscal steroids. A prospective double-blind
clinical trial. Spine 1992;17:S172–S175.
99. Khot A, Bowditch M, Powell J, et al. The use of intradiscal steroid therapy for lumbar spinal
discogenic pain: a randomized controlled trial. Spine 2004;29:833–836.
100. Yavuz F, Tas¸kaynatan MA, Aydemir K, et al. The efficacy of intradiscal steroid injections in
degenerative lumbar disc disease. Turk J Phys Med Rehab 2012;58:88–92.
101. Fayad F, Lefevre-Colau MM, Rannou F, et al. Relation of inflammatory Modic changes to
intradiscal steroid injection outcome in chronic low back pain. Eur Spine J 2007;16:925–931.
102. Beaudreuil J, Dieude P, Poiraudeau S, et al. Disabling chronic low back pain with Modic type
1 MRI signal: acute reduction in pain with intradiscal corticotherapy. Ann Phys Rehabil Med
2012;55:139–147.
103. Cao P, Jiang L, Zhuang C, et al. Intradiscal injection therapy for degenerative chronic
discogenic low back pain with end plate Modic changes. Spine J 2011;11:100–106.
104. Cohen SP, Wenzell D, Hurley RW, et al. A double-blind, placebo-controlled, dose-response
pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain
or lumbosacral radiculopathy. Anesthesiology 2007;107:99–105.
105. Sainoh T, Orita S, Miyagi M, et al. Single intradiscal administration of the tumor necrosis
factor-alpha inhibitor, etanercept, for patients with discogenic low back pain. Pain Med
2016;17:40–45.
106. Peng B, Zhang Y, Hou S, et al. Intradiscal methylene blue injection for the treatment of
chronic discogenic low back pain. Eur Spine J 2007;16:33–38.

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107. Peng B, Pang X, Wu Y, et al. A randomized placebo-controlled trial of intradiscal methylene
blue injection for the treatment of chronic discogenic low back pain. Pain 2010;149:124–129.
108. Zhang X, Hao J, Hu ZM, et al. Clinical evaluation and magnetic resonance imaging
assessment of intradiscal methylene blue injection for the treatment of discogenic low back
pain. Pain Physician 2016;19:E1189–E1195.
109. Gupta G, Radhakrishna M, Chankowsky J, et al. Methylene blue in the treatment of
discogenic low back pain. Pain Physician 2012;15:333–338.
110. Kim SH, Ahn SH, Cho YW, et al. Effect of intradiscal methylene blue injection for the
chronic discogenic low back pain: one year prospective follow-up study. Ann Rehabil Med
2012;36:657–664.
111. Kallewaard JW, Geurts JW, Kessels A, et al. Efficacy, safety, and predictors of intradiscal
methylene blue injection for discogenic low back pain: results of a multicenter prospective
clinical series. Pain Pract 2016;16:405–412.
112. Levi DS, Horn S, Walko E. Intradiskal methylene blue treatment for diskogenic low back
pain. PM R 2014;6:1030–1037.
113. Albert HB, Sorensen JS, Christensen BS, et al. Antibiotic treatment in patients with chronic
low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized
clinical controlled trial of efficacy. Eur Spine J 2013;22:697–707.
114. O’Dowd J, Casey A. Antibiotics a cure for back pain, a false dawn or a new era? Eur Spine J
2013;22:1694–1697.
115. Lings S. Antibiotics for low back pain? Eur Spine J 2014;23:469–472.
116. Alamin TF, Munoz M, Zagel A, et al. Ribosomal PCR assay of excised intervertebral discs
from patients undergoing single-level primary lumbar microdiscectomy. Eur Spine J
2017;26:2038–2044.
117. Klein RG, Eek BC, O’Neill CW, et al. Biochemical injection treatment for discogenic low
back pain: a pilot study. Spine J 2003;3:220–226.
118. Derby R, Eek B, Lee SH, et al. Comparison of intradiscal restorative injections and intradiscal
electrothermal treatment (IDET) in the treatment of low back pain. Pain Physician 2004;7:63–
66.
119. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal lumbar disc
derangement with intradiscal injection of hypertonic dextrose. Pain Physician 2006;9:115–
121.
120. Yin W, Pauza K, Olan WJ, et al. Intradiscal injection of fibrin sealant for the treatment of
symptomatic lumbar internal disc disruption: results of a prospective multicenter pilot study
with 24-month follow-up. Pain Med 2014;15:16–31.
121. Monfett M, Harrison J, Boachie-Adjei K, et al. Intradiscal platelet-rich plasma (PRP)
injections for discogenic low back pain: an update. Int Orthop 2016;40:1321–1328.
122. Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar intradiskal platelet-rich plasma
(PRP) injections: a prospective, double-blind, randomized controlled study. PM R 2016;8:1–
10.
123. Levi D, Horn S, Tyszko S, et al. Intradiscal platelet-rich plasma injection for chronic
discogenic low back pain: preliminary results from a prospective trial. Pain Med
2016;17:1010–1022.
124. Montesano PX, Cuellar JM, Scuderi GJ. Intradiscal injection of an autologous alpha-2-
macroglobulin (A2M) concentrate alleviates back pain in FAC-positive patients. Ortho &
Rheum Open Access J 2017;4:555634.
125. Oehme D, Goldschlager T, Ghosh P, et al. Cell-based therapies used to treat lumbar
degenerative disc disease: a systematic review of animal studies and human clinical trials.
Stem Cells Int 2015;946031.

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126. Priyadarshani P, Li Y, Yao L. Advances in biological therapy for nucleus pulposus
regeneration. Osteoarthritis Cartilage 2016;24:206–212.
127. Zeckser J, Wolff M, Tucker J, et al. Multipotent mesenchymal stem cell treatment for
discogenic low back pain and disc degeneration. Stem Cells Int 2016;3908389.
128. Pettine KA, Murphy MB, Suzuki RK, et al. Percutaneous injection of autologous bone
marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months.
Stem Cells 2015;33:146–156.
129. Pettine K, Suzuki R, Sand T, et al. Treatment of discogenic back pain with autologous bone
marrow concentrate injection with minimum two year follow-up. Int Orthop 2016;40:135–
140.
130. Noriega DC, Ardura F, Hernández-Ramajo R, et al. Intervertebral disc repair by allogeneic
mesenchymal bone marrow cells: a randomized controlled trial. Transplantation
2017;101:1945–1951.

5045
CHAPTER 102
Neurolytic Blockade for
Noncancer Pain
JOHN MACVICAR and NIKOLAI BOGDUK

Introduction
DEFINITION
Stedman’s Medical Dictionary defines neurolysis as either the selective,
iatrogenic destruction of neural tissue to secure the relief of pain, or a
procedure in which the nerve is electively freed surgically from
inflammatory tissue.1 This chapter deals with the former half of this
definition. It covers using chemical or physical means to damage
peripheral nerves focally in order to prevent the transmission of
nociceptive information along the target nerve in order to provide relief of
pain. Surgical interventions are described in Chapters 103–105.
Etymologically, the term neurolysis actually means teasing apart or
dissolving a nerve, and neurotomy means opening a nerve, but no superior
term has been advanced and accepted to refer to producing focal damage
to a nerve while leaving it intact. In this chapter, the term neurolytic
blockade has been adopted, as a general term, to refer to all procedures
whose intent is to prevent the conduction of nociceptive traffic along it.
Reflecting convention, rather than good etymologic practice, “neurolysis”
has been retained in the context of chemical procedures and “neurotomy”
in the context of physical procedures.

PRINCIPLES
Neurolytic blockade is a therapeutic option when the actual source of pain
cannot be treated. The objective is to relieve the pain by blocking the
nerves that transmit nociception from its source.
The primary indication for neurolytic blockade is complete relief of pain

5046
when the target nerve is anesthetized temporarily with controlled, local
anesthetics (see Chapter 98). Longer lasting relief can then putatively be
achieved by neurolysis or neurotomy.
Of the chemical agents, phenol and alcohol are the most commonly
used, and there are no comparative outcome data by which to choose
between the two. Glycerol has a special application in the management of
trigeminal neuralgia.
Of the physical modalities, heat and cold have both been used to
interrupt conduction along peripheral nerves. In both instances, a probe or
an electrode is placed on the nerve and is used to produce a small lesion
that incorporates a segment of the nerve. Cold lesions (cryoneurotomy) are
produced by passing carbon dioxide through a probe. Thermal lesion
(thermal neurotomy) are produced by passing a radiofrequency (RF)
current through an electrode. Variants of RF neurotomy have been
developed in which the emphasis lies in the frequency and modulation of
the current applied rather than the heat that it generates.

HISTORY AND TRENDS

The earliest form of neurolytic blockade was surgical neurectomy, in
which the nerves from a source of pain were simply transected. This
approach has largely been abandoned for several reasons. Neurectomy did
not achieve long-term results, and when pain returned, the procedure could
not be repeated, painful neuromas could develop on the proximal stump of
transected nerve, and transecting large nerves could result in
deafferentation pain.
Chemical and physical neurolytic blockades were developed to
overcome or circumvent these problems. Neuroma formation could be
avoided by not transecting the nerve. If the nerve recovered, and pain
recurred, the neurolytic procedure could be repeated. Small nerves, not
readily accessed surgically, could be targeted with electrodes or injections
in order to avoid having to target their larger, parent nerves.

LIMITATIONS
Classical pathology teaching describes how nerves recover after they have
been transected. Wallerian degeneration occurs in the distal stump and is

5047
completed within 24 hours in small nerve fibers and in 48 hours in larger
nerve fibers. In the proximal stump, regeneration of axon tubules occurs
within hours of the transection. The process is driven by neurotrophic
agents, such as tumor necrosis factor α (TNF-α), T cells, macrophages,
leukocyte inhibitory factor (LIF), and cell adhesion molecules, which are
expressed in a highly coordinated fashion.2–4 A growth cone, containing
mitochondria, vesicular elements, neurofilaments, and endoplasmic
reticulum, emerges from the proximal stump and proceeds into the distal
stump, if it is accessible; Schwann cells undergo mitotic activity and form
a framework for developing fibers.2 Regeneration occurs at a rate of
approximately 1 mm per day so that reinnervation of a structure 5 cm
away would take approximately 50 days. This process requires an intact
dorsal root ganglion to synthesize the regenerative proteins and other
nutrients.
Neurolytic blockade involves a different pathology, much of which has
not been explored and explained. The differences arise according to where
in the nerve the lesion is made, the nature of the lesion, and its size.
If the dorsal root ganglion is destroyed, regeneration will not occur
because the cell nucleus is not available to drive the process.
Consequently, not only permanent relief of pain but also permanent side
effects and complications can be expected from neurolytic procedures that
target a dorsal root ganglion.
If a peripheral nerve is targeted, chemical neurolysis does not destroy it.
Instead, the chemical applied denatures the components of the axons, in
one way or another, and only focally. Chemicals can bind to membrane
proteins or other elements, or they can exert an osmotic effect which
focally desiccates the nerve. From such processes, the nerve can recover.
All that is required is that the damaged elements be replaced in the normal
course of endocellular maintenance of the cell membrane or other
constituents. The rate at which this happens, however, has not been
established.
Cryoneurotomy works by freezing intracellular water; the ice expands
and essentially fractures the nerve membrane, thereby preventing
conduction along it. From this effect, the nerve can recover by
reconstituting the damaged segment of membrane. Based on the duration

5048
of relief of pain following cryoneurotomy, this recovery process appears to
be relatively fast: measurable in weeks.
Thermal RF neurotomy denatures all the proteins in the segment of
nerve incorporated in the lesion made. Nevertheless, the nerve remains
macroscopically intact. Regeneration does not occur by classical processes
because the nerve is sealed by the coagulated proteins, not transected, and
left open. Therefore, growth cones cannot emerge. Before the nerve can
regenerate, the coagulated material has to be removed by endocellular
repair mechanisms. The rate of this process has not been determined but
appears to be measurable in months based on the duration of effect of
thermal RF neurotomy. Critical in this regard is the length of nerve
affected. It is axiomatic that, if a short segment (1 to 2 mm) is coagulated,
recovery will be faster than if a longer segment (10 to 15 mm) is
coagulated. An appropriate simile is that endocellular repair is like
tunneling a mineshaft that has caved in; it takes longer to tunnel a longer
length of caved-in shaft.

Chemical Neurolytic Blockade

PRINCIPLES
Phenol, alcohol, and glycerol are locally neurotoxic in a dose-dependent
manner. These dehydrating agents cause a nonselective destruction of
neuronal tissues followed by necrosis, nonsegmental demyelination,
wallerian degeneration, and complete conduction block occurs within 10
minutes of application.5–12

PHENOL
First introduced by Lister in 1867 as an antiseptic, phenol (carbolic acid) is
a neurolytic agent with local anesthetic properties. Concentrations of less
than 1% produce local anesthesia without toxicity or neurolysis and may
be used as a topical anesthetic. Phenol can be injected directly onto
peripheral nerves or into the subarachnoid space in order to target dorsal
root ganglia. Nonselective neuronal destruction leading to wallerian
degeneration is its principle mode of action.

5049
ALCOHOL
Alcohol (absolute alcohol, ethanol, ethyl alcohol) is a clear volatile
hygroscopic liquid that exerts its analgesic effect by nonselective neuronal
destruction.8–10 Because of its irritant effect, alcohol may exacerbate local
pain on injection and may produce dose-dependent burning and
dysesthesia. Prior injection of local anesthetic may minimize this effect.
Alcohol has produced variable results, and some consider that the risk of
complications outweighs its benefits.8

APPLICATIONS
Alcohol or phenol has been widely used to perform neurolytic blockades
of various parts of the sympathetic nervous system of the abdomen.
Targets have included the lumbar sympathetic trunks and the splanchnic
nerves but most commonly the celiac plexus and ganglia.
In patients with visceral disorders, neurolytic blocks of the celiac
ganglion or plexus are most commonly used to treat the pain of carcinoma
of the pancreas. Various techniques are available by which to block the
celiac plexus, ranging between anterior or posterior approaches, using
fluoroscopy, computed tomography (CT), or endoscopic ultrasound, for
guidance.13 For carcinoma of the pancreas, neurolytic blocks are often
helpful to reduce pain14–17 but are not necessarily more effective than
treatment with analgesics and opioids.17–20
For the pain of chronic pancreatitis, the evidence is less robust and less
heartening. Response rates are low,13,15 and unequivocal data on efficacy,
and long-term outcomes are lacking.21
Descriptive studies promoted neurolytic lumbar sympathetic blocks as a
worthwhile treatment for rest pain in patients with peripheral vascular
disease, particularly those in whom surgery could not be performed.22–24 A
controlled trial showed that neurolytic blocks were far more effective than
local anesthetic blocks,25 but higher levels of evidence have not appeared.
Phenol or alcohol can be injected intrathecally in order to target
particular nerve roots. Mixing the neurolytic agent with glycerine produces
a hyperbaric solution, which can be guided under gravity to the target
nerve or nerves. Adding contrast medium to the solution allows the
movement of the solution to be monitored. With skillful technique, the

5050
solution can even be guided into a single nerve root pouch by
appropriately tilting the patient. In case reports and book chapters, such
injections have been promoted as a treatment for cancer pain, but there
have been no controlled trials.26 The treatment provides complete relief of
pain in up to half of the patients treated.27 The duration of effect is
measurable in weeks or months, which may be sufficient for patients with
short life expectancy. Intrathecal injections of phenol have not been
promoted for the treatment of noncancer pain.
Neurolytic blocks of the lumbar or cervical sympathetic chains have
been used, at times, for the treatment of complex regional pain syndromes,
albeit on the basis of very little published evidence. A systematic review
concluded that there is no good evidence for the effectiveness of
sympathectomy—particularly with regard to long-term effectiveness
outcomes—and it should be used with great caution if at all outside a
research context, in carefully selected patients after thorough assessment
and probably only after failure of other treatment options.28 A narrative
review concluded that no high-level evidence exists to support the
widespread use of neurolytic blocks for complex regional pain syndromes,
particularly because there is evidence to support other forms of
treatment.29
Although injections of phenol have been used to treat lumbar
zygapophysial joint pain,30 this treatment has not been widely adopted by
others and has neither been corroborated nor validated by controlled trials.

GLYCEROL
Propane-1,2,3 triol, or glycerol, is a colorless hygroscopic, syrupy liquid
that has a unique application in the management of trigeminal neuralgia.
Percutaneous retrogasserian glycerol rhizolysis is achieved by the
instilling, under fluoroscopic guidance, no more than 0.3 mL of glycerol
into the gasserian cistern. Glycerol nonselectively damages both the axons
and the myelin sheath,11 and 30% to 76% of patients suffer sensory loss.12
Some achieve good pain relief without detectable facial numbness.31 Onset
of analgesia takes about 1 to 10 days to occur but can be delayed for up to
6 weeks.31 It provides excellent pain relief while largely sparing trigeminal
nerve function in most patients.32 As many as 72% of patients can be

5051
totally free of pain for 3 years, and in one series, 60% remained pain-free
for more than 10 years after a single injection.31 Within the first year, 10%
to 53% recur,32 whereas 25% to 83% recur between 2 and 5 years.33 These
long durations of effect are concordant with the trigeminal ganglion being
the target of the treatment. Damaging ganglion cells prevents or impedes
regeneration of the peripheral nerve fibers that they subtend.
Glycerol is preferred when pain is localized to the first division as it
rarely produces corneal anesthesia, but the overall effectiveness is less
than for RF neurotomy.34 In the elderly or where microvascular
decompression is contraindicated, glycerol ganglion lysis is safer, more
effective than stereotactic surgery and is more cost-effective.35 Head-to-
head comparisons of effectiveness indicate that glycerol is at least as
effective as RF neurotomy,36 but balloon compression may be slightly
more effective than either of these procedures.37

Cryoneurotomy
Cryoneurotomy relieves pain by causing a variable degree of nerve injury.
Freezing is achieved by a simultaneous reduction in pressure and
temperature as expanding carbon dioxide is forced through a specialized
probe. An ice ball averaging 3.5 to 5.5 mm in diameter rapidly forms at
temperatures as low as −50° to −70° C. Subzero temperatures cause
nonselective but reversible conduction block, and the effect is prolonged
when the intracellular contents are crystallized. There is little clinical
difference provided that the temperature is maintained below −20° C for 1
minute.38,39
Nerve injury is dose dependent and ranges from a mild “neurapraxia” to
changes of wallerian degeneration, associated with very minimal
inflammatory reaction. Within a few days of freezing, the lesion is seen as
a dense cellular matrix of macrophages.40 In contrast to chemical
neurolysis, painful neuromas, neuritis or dysesthesia is avoided as exact
regeneration is facilitated by an intact epineurium and perineurium.38,39
The duration of the block depends on the rate of nerve regeneration at the
proximal stump, which averages 1 to 3 mm per day.38,39 Cryolesioning is a
safe, simple, and repeatable procedure: It produces a temporary block, and

5052
its therapeutic effect may last for many weeks. The main disadvantage is
that the relief of pain is often of short duration and unpredictable.41
Cryotherapy has been used by some as an effective adjunct to the
pharmacologic management of trigeminal neuralgia when other more
invasive treatments are contraindicated. In most patients, the relief of pain
is immediate, and in one series, at least 58% remained pain free for 12
months with a mean time to recurrence of 20 months.42
For chronic lumbar zygapophysial joint pain, modest outcomes have
been noted in two studies. One study claimed a 72% success rate 6 weeks
after cryotherapy.43 The other found that 62% of patients reported at least
50% relief of pain for 12 months, with parallel improvements in activities
of daily living.44
Cryoneurotomy has been reported as useful for the management of
postthoracotomy pain and intercostal neuralgia.45 In these conditions, the
short duration of relief obtained may be enough to render patients
comfortable while natural healing occurs or other measures are
implemented.

Thermal Radiofrequency
INTRODUCTION
Thermal (continuous) percutaneous RF procedures have now evolved as
one of the better and more practical neurosurgical procedures for the
management of chronic disabling pain. With modern imaging and the
development of sophisticated equipment, precise ablation of neural
pathways is possible. When meticulously executed in correctly selected
patients, RF neurotomy with temperature monitoring has proven itself to
be safer and more effective than any other procedure. The technique
required principally depends on the source of nociception and the
accessibility of the nerves that innervate it. Critical to its correct
application is an understanding and appreciation of its limitations, the
pathophysiology of the primary condition, and a valid diagnosis.

PHYSICS
Thermal RF should not be confused with electrocautery. Tissues are not

5053
burned or oxidized. Rather, they are coagulated in situ by the application
of a high-frequency, alternating electric field.46 The objective of RF
lesioning is to deliver sufficient heating power into biologic tissue such
that the tissue temperature is raised above the “lethal temperature” range
of 45° to 50° C. Neural cells exposed to these temperatures for 20 seconds
or more will be destroyed by heat.47,48 This requires an RF generator, an
insulated electrode with an exposed (“active”) tip of 2 to 10 mm, and a
ground or dispersive (“passive”) plate with a large surface area.49 The
electrode is placed either into (central nervous system) or onto (peripheral
nerve) the target structure. The larger dispersive plate is placed at a
convenient location of the body remote from the electrode. The patient
completes the electrical circuit, and the generator delivers the alternating
current between exposed tip of the insulated electrode and the large
dispersive plate.
The passage of low-energy, high-frequency alternating current (100,000
to 500,000 Hz) causes intense oscillation of ions. This oscillation heats
charged molecules, notably proteins.50 The exposed, active tip of the
electrode acts as an antenna, around which the current concentrates into a
greater density. Consequently, greater heating occurs in the tissues around
the electrode, and it is the tissue about the electrode tip, rather than the
electrode itself, that becomes the source of heat. The tissues heat the
electrode, and a thermocouple, built into the electrode, monitors the
temperature generated. Once a certain temperature is reached, lesion
formation (“coagulation”) occurs.
Tissue temperature (T) is related directly to current density (I) but
inversely to the fourth power of the radius (R) from the electrode, that is, T
= IR−4. Current density is less at the distal tip of the electrode than at its
sides. Therefore, the lesion extends little, if at all, in a longitudinal
direction from the tip. Rather, it extends radially around the circumference
of the exposed shaft and generally assumes the shape of a prolate spheroid
(football).50 However, because the tissue temperature drops rapidly with
distance from the electrode, the lesion is limited in size, to 2 mm or less
beyond the surface of the electrode (Fig. 102.1).

5054
FIGURE 102.1 Longitudinal sections through thermal radiofrequency electrodes, showing the
geometry of the lesions that they produce. The lesion has a transverse radius (r) that is proportional
to the width (w) of the electrode. Less lesion is produced distally (d). For the same electrode on
different occasions, the size of the lesion varies around a mean value in a normal distribution.
Smaller electrodes generate smaller lesions. Smaller lesion may fail to incorporate a target nerve (n)
completely, even if the electrode is placed close to the nerve.

The physical variables that govern lesion size include current density, its
rate of application, lesioning temperature, electrode size, the duration of
heating, and impedance.48,50–52 Temperature is the fundamental lesioning
parameter, and temperature monitoring remains central to the safety of the
procedure and quantification of lesion size.53,54 Because there is no
consistent relation between temperature and voltage, temperature-
controlled RF lesioning is preferred to voltage-controlled lesioning in
order to create reproducible and well-defined lesion sizes.55 The use of
lower temperatures may not be acceptable in the clinical setting because it
may not produce a permanent or long-term or sufficiently extensive lesion.
Above 60° C,56,57 soft tissues generally will coagulate, and if the surface
temperature of the electrode is elevated to 80° to 85° C, then tissues within
a short distance from the surface will be heated to 60° to 65° C or more.
Once the electrode surface temperature reaches 80° C, lesion size increases
with time as the temperature is maintained. Most of the increase in size
occurs within 60 seconds, but an appreciable growth continues between 60
and 90 seconds.57 After 90 seconds, further growth is prevented because
the coagulated tissues present an increasing impedance (resistance) to flow
of current and, therefore, the generation of any further lesion.
The lesion should be generated by increasing the temperature by about

5055
1° C per second. This avoids cavitation, steam formation, microexplosions,
and charring,48,50,51 but more critically in the event that the patient
experiences adverse sensations, heating can be aborted promptly, before
the temperature rises too high and any damage is done.49
The size of the lesion is directly proportional to the diameter (width) of
the electrode. Because lesions develop from the surface of the electrode,
those formed by a larger electrode will reach further away from its center.
Lesions made by small-diameter electrodes will extend only a short
distance from their surface (see Fig. 102.1). In practice, the radius of a
lesion is equal in length to between 1 and 2 times the width of the
electrode used. Beyond this range, tissues may escape coagulation.49,57
Because electrodes generate lesions radially, they must be placed close
and parallel to the target nerve in order for the lesion to be optimally
effective.49,56 If the electrode is placed perpendicular to the nerve, the
lesion made may fail to incorporate the target nerve (Fig. 102.2).
Throughout the lesioning process, the electrode must be held in place lest
it dislodges, and its proper placement should be checked by periodic
fluoroscopic monitoring.

FIGURE 102.2 The influence of orientation on the effects of thermal radiofrequency neurotomy.
A: If an electrode is placed perpendicular to the target nerve, it may coagulate the nerve only
partially and for a short length because of the limited range over which the electrode generates a
lesion distally. B: If an electrode is placed parallel to a nerve, it incorporates a large volume of the
nerve along a greater length.

PATHOLOGY
Heating by RF causes many cells to die rapidly at temperatures greater

5056
than 45° C. Similar effects are produced irrespective of whether the
electrode is placed either inside the dorsal root ganglion or onto a
peripheral nerve. Above 55° C, there is an indiscriminate destruction of
both small and large myelinated fibers, focal necrosis, hemorrhages,
extensive edema, and features of wallerian degeneration.58–63 Even with a
low voltage of 0.1 V, an electrode placed inside a dorsal root ganglion and
heated to 67° C causes a total loss of myelinated fibers, with
hemorrhages.63

PHYSIOLOGY
The study by Letcher and Goldring64 is often misrepresented as showing
that RF neurotomy selectively destroys small-diameter fibers while
preserving large-diameter fibers. Rather, what the study showed was that
depression of C-fiber and Aδ-fiber action potentials preceded depression
of the potentials of Aβ fibers, but, within in a short time, all fibers were
ultimately and equally affected, and the disappearance of action potentials
was independent of fiber size. No class of fiber was exempt from the
effects of heat.64 These findings were confirmed in two independent
clinical studies which showed that RF neurotomy of the medial branches
of the lumbar dorsal rami resulted in electromyographic abnormalities in
over 80% of patients.65,66 These abnormalities indicated that large-
diameter α motor neurons were not spared by RF neurotomy.

APPLICATIONS
In general medicine, thermal RF is widely used for the treatment of
supraventricular tachyarrhythmias.67 Water-cooled electrodes permit the
generation of larger lesions to ablate thick ventricular muscle effectively.68
In pain medicine, thermal RF has been used to treat trigeminal neuralgia,
to interrupt pain pathways in the spinal cord or brainstem, and to treat
various types of spinal pain and miscellaneous other types of pain.

Trigeminal Neuralgia
For the symptomatic treatment of trigeminal neuralgia, various descriptors,
such as RF trigeminal neurolysis, RF thermocoagulation of the gasserian
ganglion, or retrogasserian thermorhizotomy, each refer to the generation

5057
of thermal lesions in an area between the trigeminal ganglion and its
sensory root. Under fluoroscopic guidance, the electrode is introduced via
the foramen ovale until the active tip sits at the posterior end of Meckel’s
cave, the average depth of insertion being 5 to 6 cm. Once the electrode
appears to be adequately placed, a test electric stimulus is delivered to the
nerve. If the electrode has been accurately placed, test stimulation will
evoke pain in the area in which the patient normally experiences pain.
Lesioning temperature may range between 55° and 90° C,33,69,70 and the
current may be applied either continuously for up to 300 seconds69 or in
45- to 90-second cycles.70
The evidence of effectiveness for trigeminal RF neurotomy consists of
several, large, observational studies, some encompassing over 1,000
patients.71 In one series, 41% of patients sustained relief for 20 years.70
However, because of methodologic inconsistencies, a systematic review72
found only four studies on which sound conclusions could be
based.69,70,73,74 Nevertheless, collectively, these studies reaffirmed the
general, favorable impression conveyed by the literature at large.
Compared with other, commonly used, ablative techniques, RF neurotomy
provided the highest rate of complete pain relief: Some 75% of patients
were free of all pain for at least 6 months. At 12 months, RF provided a
higher rate of complete pain relief than stereotactic radiosurgery.72 In a
later, unrelated study,75 90% of patients reported complete pain relief from
their first RF, and a significant proportion continued to enjoy excellent
relief some 15 years later. Presumably due to neuronal regeneration, the
success rate diminishes and pain returns such that just over 50% remain
completely relieved at 5 years72 with a 14-year recurrence rate of 25% in
one series.75
Common side effects are sensory loss, sufficient to affect quality of life,
in more than 30% of patients; keratitis in some 10%; and dysesthesia in
4% to 10%. Although rare, reported complications include cranial nerve
palsies, brainstem injury, meningitis, and vascular fistula formations.76–79

Central Ablative Procedures

In conditions where pain is intractable and refractory to most forms of
nonsurgical and minimally invasive interventions, relief may be secured by

5058
interrupting pathways in the spinal cord.80 The most common target sites
are the dorsal root entry zones, the spinothalamic tract, and trigeminal
pathways.

Dorsal Root Entry Zone Lesions

Dorsal root entry zone (DREZ) lesioning is performed for the relief of
central (deafferentation) and peripheral (neuropathic) pain caused by
disease of peripheral nerves or injuries to them.80,81 In these conditions,
deafferentation results in spontaneous activity in the apical neurons of the
dorsal gray column of the segments to which the affected nerves relay.82
DREZ lesioning involves inserting a small electrode into this region in
order to ablate the spontaneously active cells.81 Multiple lesions are
usually required in order to capture all the active neurons. Better outcomes
are obtained when the dorsal root and the dorsal horn are primarily
affected by the injury and both the pain and the pathology are
topographically well defined. Conversely, DREZ lesioning is
contraindicated where pain is poorly localized because identifying the
level at which the operation should be performed is difficult.80 The
ablative process includes the central portion of the dorsal root, the tract of
Lissauer, and layers I to V of the dorsal horn. In this manner, the lateral
portion of the dorsal horn, where C fibers predominate, is destroyed. By
sparing the medial portion of the dorsal horn, tactile and proprioception
senses are preserved.
Better outcomes are obtained if test electrical stimulation is used.
Stimulation not only confirms the relevant segments but also identifies
additional zones of dorsal horn electrical hyperactivity which would have
been missed if topographical landmarks alone are used.83,84
Controlled trials have not been performed, but this may be
understandable given the nature of the disorder and the nature of the
intervention. Advocacy is based on multiple observational studies in which
significant proportions of recipients report remarkable relief. DREZ
lesioning has been particularly effective for the pain of brachial plexus
avulsion with 66% and 87% patients affirming more than 70% relief,85–94
and an appreciable proportion not requiring supplementary medication.86
For traumatic spinal cord injuries, percentage relief of pain can range from

5059
at least 50% to complete relief with no limitation of activity or the need for
opioids,94–96 but a recent review found the published evidence to be
limited.97 With respect to postamputation pain, the outcomes are better for
phantom pain than for stump pain alone.86 DREZ lesioning has not been
particularly effective for postherpetic neuralgia. Some 18% to 47% report
complete pain relief, but such relief is not consistently maintained.85 The
close neuroanatomical relationship between the site of DREZ lesioning,
the lateral corticospinal tract, and the dorsal column can lead to severe
neurologic complications such as motor weakness, bladder or sexual
dysfunction, and dysesthesia (see Chapter 107).98

Brainstem Procedures
Pain subtended by the nucleus caudalis of the trigeminal nerve can be
treated by ablating various sites within the brainstem, such as the
descending trigeminal tract (trigeminal tractotomy), the nucleus caudalis
(trigeminal nucleotomy), or all of the substantia gelatinosa of the nucleus
caudalis (nucleus caudalis dorsal root entry zone, NCDrez). Nociceptive
type pain is most sensitive to NCDrez ablation.85 Indications have
included severe glossopharyngeal neuralgia, craniofacial dysesthesia,
posttraumatic neuropathy, atypical facial pain, complex craniofacial pain,
and anesthesia dolorosa.94,99–101 For intractable facial pain, such as “end-
stage” trigeminal neuralgia that has failed all other means of treatment
including microvascular decompression, DREZ lesioning of the nucleus
caudalis has been successful in 60% to 70% of cases.102,103

Cordotomy
Percutaneous cordotomy can be used to treat unilateral intractable pain
transmitted by the lateral spinothalamic tract.99 A lesion made in the
anterolateral segment of the spinal cord totally abolishes pain and
temperature in one-half of the body below the lesion.99 The procedure is
typically performed percutaneously at the C1–C2 level, using a lateral
approach to insert the electrode. Indications for these procedures have
included severe neuropathic pain arising from brachial plexus root
avulsion imitating phantom pain, electric burns, postherpetic neuralgia,
and cancer pain.104 In patients with cancer pain, some 70%105 or

5060
more106,107 initially obtain worthwhile relief. This relief wanes with time
but persists in most for the duration of remaining life.

Medial Branch Neurotomy

Medial branch neurotomy is a procedure in which an RF electrode is used
to coagulate one or more medial branches of the dorsal rami of the spinal
nerves.108,109 The strictest, taxonomically purest definition of the
indication for the procedure is that it is used to treat pain mediated by one
or more medial branches. A corollary of this definition is that the
indication requires complete relief of pain when the target nerve or nerves
is anesthetized using controlled diagnostic blocks (see Chapter 98).
However, the medial branches of the dorsal rami have a restricted
distribution. They supply the zygapophysial joints and certain of the
posterior spinal muscles. These muscles, however, are innervated in a
myotomal fashion such that only those fascicles stemming from a
particular spinous process are innervated by the nerve of the same
segmental number. There are no known disorders that affect selectively
only particular myotomes of the back muscles.110,111 Therefore, the most
likely sources of pain mediated by medial branches are the zygapophysial
joints. Consequently, medial branch neurotomy has come to be regarded as
a treatment for zygapophysial joint pain. However, stipulating the actual
source of pain is immaterial, for the indication for treatment is relief of
pain after blocking the nerve or nerves that mediate the pain.

Lumbar Medial Branch Neurotomy

Background. The history of lumbar medial branch neurotomy is replete
with misconceptions, errors, and misrepresentations. These apply both to
surgical technique and to patient selection.
The original version of the procedure—known as “facet
denervation”112–115—was based on the concept that coagulating articular
nerves would relieve pain from the zygapophysial (“facet”) joints. An
abundant literature followed, with many studies claiming remarkable
success for relieving back pain.108 However, it was subsequently shown
that there were no nerves in the location where electrodes were
placed.116,117 This converted the procedure to a sham.

5061
 At the same time, it was shown that the only suitable targets for
denervating a zygapophysial joint were the medial branches that supplied
the joint.116,117 Consequently, the procedure was renamed medial branch
neurotomy.117 Furthermore, the practice became to place the electrode
perpendicular to the nerve.118 However, some 7 years later, it was shown
that perpendicular placements risked missing the nerve, or capturing it
only partially (see Fig. 102.2).56 The resultant revision was to place the
electrode parallel to the nerve in order to capture a maximal thickness of
the nerve and a maximal length of it in the lesion created by the
electrode.56
Studies showed56,57,119 that large-gauge (16 gauge) electrodes made
larger lesions and were more likely to capture the target nerve than would
small-gauge (20- to 22-gauge) electrodes. If smaller electrodes were used,
they had to be in direct contact with the nerve in order to capture it.
Displacements as little as 1 mm could result in failure to capture the nerve.
Furthermore, it became apparent that the exact location of the nerve
could vary, by up to a few millimeters.119 Therefore, a single target point
could not be used. Instead, in order to capture the nerve, multiple lesions
need to be made across the target zone in which the nerve could lie. The
smaller the gauge of the electrode used, the greater the number of lesions
that needed to be made in order to fully coagulate the target zone.108
Despite the research over 20 years that established these principles, not
all surgeons have heeded them. They have developed, used, and continue
to use flawed techniques, despite warnings publicizing these flaws.120,121
Electrodes have been placed in locations where nerves are not located,
which renders the procedure a sham. Electrodes have continued to be
placed perpendicular to the nerve, which risks coagulating the nerve
inadequately and, therefore, lowering the success rate, the degree of relief,
and its duration.
A different set of confounding influences pertains to patient selection.
They relate to the validity of diagnosis and its subsequent effects on the
success of treatment.
The paradigm of medial branch neurotomy is that the patient’s pain
must be relieved by prior diagnostic blocks.108 If the pain is not relieved,
there is no logic using medial branch neurotomy to treat the pain, for the

5062
patient does not have the condition for which the treatment is designed.
The strictest operational criteria for diagnostic medial branch blocks are
that the patient’s pain must be completely relieved by double-blind
controlled blocks and that relief is accompanied by restoration of activities
of daily living previously impeded by the pain.122 Any deviation from
these criteria threatens the validity of the blocks.
Single diagnostic blocks are not valid. Not only do single blocks fail to
identify the 34% or so of patients who fail to get any relief when a block is
repeated,123 they also have false-positive rates that range between 25% and
45%.124–129 Depending on the prevalence of the condition, such false-
positive rates mean that even if the patient reports complete relief of pain,
up to 60% or more of patients will not actually have the condition being
tested. In turn, that means that up to 60% of patients will not respond to
treatment, except perhaps through a placebo effect.
For diagnosis to be valid, diagnostic blocks must be controlled.
Vexatious, however, is the type of control that should be used. That, too,
depends on the prevalence of the condition. For common conditions, such
as cervical zygapophysial joint pain, lesser controls are adequate. For less
common conditions, such as lumbar zygapophysial joint pain, tighter
controls are required in order to ensure validity.
For common conditions, comparative local anesthetic blocks are
practical.130,131 They provide a credibility of 75% if agents are fully
randomized or 50% if agents are only routinely alternated.131 For less
common conditions, diagnostic confidence plummets such that when the
prevalence is only 30% or less, as many as two-thirds of positive responses
to comparative blocks will be false.122,131 For those conditions, placebo-
controlled blocks are required for consummate diagnostic accuracy.130,131
The degree of relief from a diagnostic block is also critical. Optimally,
the relief should be complete. In that regard, nuances apply. In a patient
with pain stemming from consecutive zygapophysial joints, a physician
might have initiated investigations by anesthetizing the upper of the two
levels. In that event, the patient may report complete relief but only in the
upper part of his or her region of pain.122,132 Reciprocally, if the physician
anesthetizes the lower of the two joints, the patient may report complete
relief but only in the lower region of his or her pain. However, once both

5063
sources of pain have been correctly identified, complete relief can be
achieved by performing diagnostic blocks simultaneously of both sources
of pain. Detailed protocols for these situations are available
elsewhere.122,132
That situation is different from a patient reporting only, say, 50% relief
of all of his or her pain. Without further information, such a response is
uninterpretable. A physician cannot tell if the patient is reporting some sort
of placebo response; is uncertain of the effect of the block; does not
understand the purpose and significance of the block; or has some other,
unknown, concurrent source of pain. Although it might be convenient to
assume that the patient has a concurrent source of pain, that assumption
cannot be held to be true unless and until that other source of pain is
identified in a valid manner. However, regardless of the reason, 50% relief
pain from a diagnostic block means that, at best, the patient could not
expect better than 50% relief following treatment.
Witnessing restoration of activities of daily living is a critical
requirement of diagnostic blocks. Relief of pain is a subjective
phenomenon, but restoration of activities previously limited by pain
renders the response to a block objective122 For example, seeing a patient
being able to move freely without pain serves to confirm the positive
response to the block. Not being able to move is incongruous with a
positive response to the block.
If these various requirements are not satisfied, the validity of a block is
compromised, and poorer outcomes from medial branch neurotomy can be
expected. If blocks are not repeated in order to confirm the response, or if
controlled blocks are not used, the resultant false-positive responses mean
that large proportions of patients will not respond to medial branch
neurotomy because they do not have the condition that the treatment is
designed to treat or they will have only placebo responses to treatment. If
the patient does not get complete relief from a block, they cannot expect
complete relief from the treatment. If a block does not restore the patient’s
activities of daily living, they cannot expect the treatment to do so. These
various features have confounded much of the literature concerning the
evidence for the effectiveness of medial branch neurotomy.

5064
Technique. The one technique for lumbar medial branch neurotomy that is
based on the research literature concerning the anatomical basis for this
procedure, and for which there is evidence of effectiveness, is that
described by the Practice Guidelines of the International Spine
Intervention Society.108 Details for the conduct of that procedure are
provided in those guidelines. Figure 102.3 illustrates the critical features.

FIGURE 102.3 Fluoroscopy views of an electrode in place for an L4 medial branch

radiofrequency neurotomy. A: Declined (pillar) view showing the tip of the electrode lodged in the
notch between the superior articular process and transverse process of L5. B: Oblique view showing
the tip of the electrode crossing the junction of the superior articular process and transverse process.
C: Posteroanterior view showing the electrode orientated obliquely, cephalad and medially, against
the lateral surface of the superior articular process. D: Lateral view showing the active tip of the
electrode lying opposite the middle two-fourths of the neck of the superior articular process.

The electrode must be inserted so that its tip lies parallel to the target
nerve. This requires an insertion from below, along a ventrorostral
trajectory (Fig. 102.3A). The electrode must also avoid the
mamilloaccessory ligament. Therefore, the trajectory must also be slightly
abducted (Fig. 102.3C). The electrode is inserted until its tip enters the
target zone for the medial branch, which lies opposite the middle two-
quarters of the neck of the superior articular process.108,119
Because of idiosyncrasies in anatomy, for the L1–L4 nerves, the target

5065
is the medial branch. At L5, the target is actually the L5 dorsal ramus
itself. It is the L5 dorsal ramus, rather than the L5 medial branch, that
crosses the target zone opposite the middle two-quarters of the neck of the
S1 superior articular process.108,110,119
Once the electrode has been placed, the tissues surrounding its tip are
coagulated by raising the temperature of the electrode to 80° to 85° C for
90 seconds. However, for optimal outcomes, adjustments have to be made
to cater for the gauge of the electrode and the length of its exposed tip. A
single lesion may not be adequate to ensure capturing the entire nerve.
Because the nerve may lie slightly higher or slightly lower on the neck of
the superior articular process, lesions may need to be placed high and low
in the target zone. This is less of an issue if large-gauge electrodes are
used, for such electrodes form large lesions that can encompass the entire
height of the target zone, but if smaller electrodes are used, two or three
placements may be required in order to encompass the entire target
zone.108 If the exposed tip of the electrode is only 5 mm, lesions may need
to be made both distally and proximally along any given insertion, in order
to capture a maximal length of the nerve.108 If these precautions are not
taken, either the nerve may escape coagulation or be only partially
coagulated, either of which consequence compromises the outcome of the
treatment.

Effectiveness. The effectiveness of this technique of lumbar medial branch

neurotomy was benchmarked by two studies. Both studies selected patients
for treatment on the basis of responses to comparative local anesthetic
blocks. Both placed large-gauge electrodes parallel to the target nerves,
across the target zone for each nerve.
The earlier study selected patients on the basis of greater than 80% relief
from pain following each of two diagnostic blocks.66 Anatomical success
in coagulating the target nerves was confirmed by postoperative
electromyography of the myotomes of the nerves coagulated. At 12
months after treatment, 80% of patients continued to have at least 60%
relief of pain, and 80% had at least 60% relief.
The later study was conducted in two neighboring practices.133 The data
from each practice differed only in that one practice performed treatments

5066
over a longer period of survey and performed more repeat treatments when
pain recurred. Patients were selected on the basis of complete relief of pain
following comparative local anesthetic blocks. Successful outcome was
defined as complete relief of pain for at least 6 months, accompanied by
restoration of activities of daily living and no need for continuing care for
back pain. In the two practices, the initial success rates were 58% (44% to
72%) and 53% (40% to 66%). In the first practice, the median duration of
relief from the first treatment was 15 months, with an interquartile range of
10 to 28 months. In the second practice, the corresponding figures were 15
(10 to 29) months. Repeat treatments were performed to reinstate relief if
pain recurred after the first treatment. A total of 35 treatments in 29
patients were performed in the first practice, and 66 treatments in 30
patients in the second practice, resulting in a median duration of relief, per
treatment, of 13 months, over a 5-year period.
These data established that good outcomes could be achieved if patients
were correctly selected using controlled diagnostic blocks and if
meticulous surgical technique was used. Moreover, a success rate of over
50% for achieving complete relief of pain, with restoration of activities of
daily living and no need for continuing care is unprecedented in the
treatment of back pain.
Other studies, including controlled trials, have not matched these
outcomes, but nor have they applied the same discipline and rigor, either
for selection of patients, for surgical technique, or both. Consequently,
none of the other literature constitutes legitimate evidence concerning the
effectiveness or efficacy of lumbar medial branch neurotomy as prescribed
by the International Spine Intervention Society. Any evidence that other
studies provide pertain to other variants of this procedure.
This distinction has been overlooked or ignored by authors of systematic
reviews. Any objective appraisal of the evidence requires stratifying the
data according patient selection and surgical technique, for variations in
those domains seriously compromises the outcomes achieved. Not making
the distinctions creates a false impression of the effectiveness of lumbar
medial branch neurotomy.
Relying on single blocks to select patients and not using controlled
blocks does not provide a valid diagnosis. The high false-positive rates of

5067
single blocks means that the study sample will be contaminated by patients
who are unlikely to have the condition that lumbar medial branch
neurotomy is designed to treat. Indeed, it has been shown that success rates
are significantly lower in patients selected by single blocks, than in those
selected by controlled blocks.134 This flaw does not compromise the
outcomes on those patients who do have the condition, but it reduces the
power of the study, particularly if it is a controlled trial. Genuine responses
to treatment will be swamped and obscured by patients with no response or
placebo responses.
Using less-than-complete relief of pain as a selection criterion
compromises the validity of diagnosis and the outcomes achieved by
treatment. A criterion of 50% relief means that no patient can be expected
to achieve the benchmark standard of complete relief of pain. Nor can they
be expected to restore activities of daily living or cease health care, which
are also the benchmark standards for lumbar medial branch neurotomy.
For statistical purposes, this may or may not be a fatal problem in
controlled trials. The trial could still show that a greater proportion of
patients achieved 50% relief after active treatment, but such an outcome
would be of questionable value if it does not reduce the burden of illness,
that is, the patients still have a complaint that requires continuing
treatment.
Placing the electrode perpendicular to the target nerve incurs the risk of
not coagulating the nerve adequately. In turn, this risks reducing the
success rate for achieving complete relief of pain or reducing the duration
of relief. Likewise, creating a single lesion at a single target site, rather
than coagulating an entire target zone, risks inadequate coagulation of the
target nerve. The same applies to using small-gauge electrodes. In both
instances, both the success rate and the duration of relief can be
compromised.
A fatal flaw applies to techniques in which the electrode is placed at
locations remote from any known nerve or insufficiently close to the target
nerve to capture it. Such techniques, by definition, constitute a sham
procedure. Neurotomy cannot be a genuine procedure if no nerve is
coagulated.
Throughout the literature, outcomes inferior to those of the benchmark

5068
studies can be traced to one or more of these flaws. In some instances, the
flaws disqualify the study from providing any evidence. In others, certain
conclusions can be drawn but not others.
In two explanatory controlled trials, electrodes for active treatment were
placed remote from any target nerve.135,136 These studies constitute
comparing one sham with another. The authors of one of these studies later
acknowledge this flaw.137
Perpendicular placement of electrodes is characteristic of studies
emanating from The Netherlands or influenced by them. The earliest of
these studies described but did not illustrate the technique used,138 so it is
not exactly clear where the electrode was placed. Nevertheless, sham
treatment was rigorously compared with active treatment. The success rate
of active treatment was low, ostensibly because single blocks were used to
select patients or because a single lesion was made perpendicular to the
target nerve, using a small electrode. Consequently, it was difficult to
show statistically significant difference by a simple comparison of success
rates. However, survival analysis clearly showed that success over time
was significantly greater after active treatment.138
Another explanatory study from The Netherlands found no significant
difference in favor of active treatment.139 However, small-gauge
electrodes were used; single lesions were made, perpendicular to the target
nerve; and the illustration of the technique showed that electrodes were not
placed sufficiently near to the target nerve.121 The authors acknowledged
these limitations but explained that they tested how RF neurotomy was
performed in their community, that is, The Netherlands.140 Therefore, the
conclusions from this study cannot be generalized to other techniques of
lumbar medial branch neurotomy; they expressly apply only to how it is
practiced in The Netherlands.
A second explanatory study from The Netherlands found no attributable
effect from active RF neurotomy compared with sham.141 However,
patients were selected on the basis of a decrease in pain of only 2/10
following a single diagnostic block, small-gauge electrodes were placed
perpendicular to the target nerve, and only a single lesion was made at
each site.
A more recent study from The Netherlands reported that adding

5069
neurotomy to conservative treatment did not improve outcomes.142
However, patients were selected by single blocks, and although the
surgical technique used was not illustrated, the authors—when
challenged143–145—responded that they studied how neurotomy was
practiced in The Netherlands.146 Therefore, although their conclusion
might apply to practice in The Netherlands, they do not apply to other
techniques of lumbar medial branch neurotomy.
One controlled study used correct surgical technique but selected
patients by single blocks only.147 Consequently, the data do not lack
validity but are compromised by less than optimal success rates. Even so,
the study showed that lumbar medial branch neurotomy was significantly
more often effective than a credible sham comparator.
Two studies selected patients by comparative local anesthetic blocks,
and each used correct surgical technique. The first was an observational
study.148 Patients were selected if they reported at least 70% relief of pain
following comparative medial branch blocks. Of 174 patients reviewed
over a 10-year period, 35% (29% to 41%) of patients had at least 50%
relief of pain, and a further 22% (16% to 28%) had 80% relief of pain, at 6
months after treatment. The proportions of patients with enduring relief
decreased between 6 months and 2 years after treatment, but the median
duration of relief was 12 months. A later, placebo-controlled trial149
showed that patients reported significantly greater relief of back pain after
active treatment, but this study was compromised because patients had
other complaints of pain, such as radicular pain. Consequently, a success
rate for complete elimination of pain could not be determined.
No controlled trial has shown that the results of lumbar medial branch
neurotomy—when performed correctly—are attributable to placebo. Yet, a
small number of controlled trials, with limitations, have shown that the
outcomes of lumbar medial branch neurotomy cannot be attributed to
placebo. Those controlled trials that claim no benefit beyond that of
placebo are all compromised by suboptimal selection of patients and
discredited surgical technique.

Cervical Medial Branch Neurotomy

Background. The principles of surgical precision that beset lumbar medial

5070
branch neurotomy were established before cervical medial branch
neurotomy was extensively used. Therefore, its literature is less affected
by errors and misrepresentations. Nonetheless, some problems still apply.
In strictest terms, cervical medial branch neurotomy is used to treat pain
mediated by one or more of the medial branches of the cervical dorsal
rami.109 In practical terms, it is used to treat cervical zygapophysial joint
pain. At typical cervical levels, each zygapophysial joint is supplied by the
two medial branches with the same segmental numbers as the joint.111 The
C2–C3 joint is supplied by one nerve: the third occipital nerve, which is
the superficial medial branch of the C3 dorsal ramus.111
The singular indication for cervical medial branch neurotomy is
complete relief of pain when one or more medial branches is anesthetized
by controlled diagnostic blocks.109,132 Typically, this means both of the
nerves that innervate a particular zygapophysial joint or the third occipital
nerve when the C2–C3 joint is the source of pain.

Technique. A particular idiosyncrasy that affects cervical medial branch

neurotomy is that cervical medial branches follow a curved path around
the waist of the cervical articular pillars. Therefore, in order to capture
fully a long length of the target nerve, electrodes have to be placed along
each of two paths: a sagittal path to capture the nerve on the lateral aspect
of the articular pillar and an oblique path to capture it on the anterolateral
aspect.111,132,150
The one technique that has been based on original anatomical and
laboratory research is that promoted in the Practice Guidelines of the
International Spine Intervention Society.109 It is also the only technique
that has been validated in clinical studies and trials. The Practice
Guidelines describe in detail how cervical medial branch neurotomy
should be performed.109 Figure 102.4 illustrates the key features.

5071
FIGURE 102.4 Fluoroscopy view of electrode placements in the execution of a C5 medial branch
radiofrequency (RF) neurotomy. A: Lateral view of an oblique insertion. The tip of the electrode
lies over the anterolateral surface of the C5 articular pillar. (A block needle remains in place over
the target area, in case supplementary local anesthesia is required.) B: Posteroanterior view of an
oblique insertion. The tip of the electrode lies just medial to lateral margin of the silhouette of the
C5 articular pillar. C: Lateral view of a sagittal insertion. The tip of the electrode lies over the
lateral surface of the C5 articular pillar. D: Posteroanterior view of a sagittal insertion. The tip of
the electrode lies tangential to the lateral surface of the C5 articular pillar.

In order to reach the proximal end of the target nerve, the electrode is
inserted along a 30-degree oblique path so that its tip lies against the
anterolateral aspect of the articular pillar (see Figs. 102.3A and 102.3B).
That portion of the nerve is coagulated by raising the temperature around
the tip of the electrode to 80°C for 90s. In order to reach the next section
of the nerve, the electrode is inserted along a sagittal path so that its tip lies
tangential to the lateral aspect of the articular pillar (see Figs. 102.3C and

5072
102.3D).
For nerves at different segmental levels the target zone differs.57,109 At
the C4 and C5 levels, the target zone lies opposite the central half of the
articular pillar. At higher and lower segmental levels, the target zones lie
progressively higher on the pillar.

Efficacy. This technique was developed initially on the basis of

anatomical studies111 but subsequently refined in the light of pilot clinical
studies.150 Once perfected, it was rapidly subjected to a placebo-controlled
trial.151 That trial showed that active treatment was significantly more
effective than sham treatment both in terms of success rate and duration of
relief. In that study, and in those that followed, the definition of success
was complete relief of pain, accompanied by restoration of activities of
daily living and no need for other health care.
Subsequent studies performed long-term follow-up of the patients
treated in the placebo-controlled trial and patients treated after the trial.152
Other studies corroborated the outcomes and provided additional
details.153,154
Complete relief of pain is achieved in some 70% of patients
treated.150–154 Errors in diagnosis account for the failures. Some patients
have false-positive responses to diagnostic blocks, even when these are
controlled. In other patients, neurotomy unmasks latent or previously
undiagnosed sources of pain, for example, at adjacent segmental levels.
The pooled data indicate that about 60% of patients maintain complete
relief of pain at 6 months, and between 30% and 50% do so at 12
months.155 Success rates are not demonstrably different between patients
with legal claims and those without.151–154 Recurrence of pain is to be
expected because the treated nerves regenerate, but repeat neurotomy
reinstates relief. Repetition has been reported to reinstate relief up to seven
times, with the average duration of relief ranging between 8 and 18 months
per repetition.57,152–154
Complete relief of pain is accompanied by restoration of activities of
daily living and no need for other health care.57,154,155 These outcomes
occur only if the technique recommended by the International Spine
Intervention Society109 is used and only if the selection criteria are

5073
complete relief of pain following controlled diagnostic blocks of the
medial branches to be targeted.155 If lesser diagnostic criteria are used,
success rates and the degree of relief are substantially lower.156,157
Conspicuously, RF medial branch neurotomy is the only treatment that
has been shown to provide complete relief of chronic neck pain, with
restoration of activities of daily living and no other need for health
care.57,151,155 Moreover, it also resolves psychological distress
immediately upon relieving pain158,159 and reduces central sensitization
and hyperalgesia.160 No other treatment for chronic neck pain has been
shown to have these properties. A Cochrane review found that the
evidence for cervical RF neurotomy was limited, but only in the sense that
there have not been more controlled trials; there was no dispute concerning
the quality of the published studies.161 An independent review reported
that RF neurotomy sets a benchmark for the treatment of chronic neck
pain.162
The rare side effects of cervical medial branch neurotomy include
vasovagal syncope, dermoid cyst, Koebner phenomenon, and so-called
neuritis: ostensibly, irritation of one of the target nerves.57,163 More
common side effects are numbness or dysesthesia in the cutaneous
territory of one of the target nerves.57,163 These have been self-limiting and
not requiring treatment. None is permanent because the target nerve
regenerates.
Skin burns are avoided by using a firmly applied dispersive/ground plate
with a large surface area rather than a spinal needle to dissipate electrical
energy. Meticulous technique and strict asepsis should guard against
infection and hematoma formation. Neurologic complications are avoided
by ensuring that electrodes always remain external to the vertebral column
and do not reach either the vertebral artery or the intervertebral
foramen.109
Concerns that denervating a zygapophysial joint could cause Charcot
joints164,165 are unfounded. There are no published reports of Charcot
arthropathy directly attributable to RF neurotomy. Modern
pathophysiology implicates a neurovascular mechanism, and diabetes has
replaced tertiary syphilis as the most common cause of Charcot
arthropathy,166 and arthropathy can occur in advance of abnormal

5074
neurology.167,168 Charcot joints classically occur in weight-bearing joints
of the lower limb in which all the surrounding muscles are insensate,
resulting in instability.169 This does not occur with spinal RF neurotomy.
The medial branches innervate only the deep paramedian muscles. The
superficial and lateral muscles are spared. Thus, the spinal motion segment
is not rendered insensate. Meanwhile, the disk and articular processes
maintain stability passively.
Catastrophic, spinal cord injuries have occurred only when electrodes
have been egregiously misplaced.170 They are avoided by careful
placement of electrodes into the correct target zone and monitoring their
location during the generation of lesions.

Third Occipital Neurotomy

RF third occipital neurotomy is a companion procedure to conventional
cervical medial branch neurotomy. Its distinction is that the target nerve is
the third occipital nerve (see Fig. 102.4), and the pain problem treated is
cervicogenic headache. The singular indication for the procedure is
complete relief of headache after controlled blocks of the third occipital
nerve.171
The Practice Guidelines of the International Spine Intervention Society
describe in detail how third occipital neurotomy should be performed.109
Figure 102.5 illustrates the key features.

5075
FIGURE 102.5 Fluoroscopy views of electrode placement for third occipital radiofrequency
neurotomy. A: Lateral view of oblique insertion of electrode. The electrode tip lies over the
anterolateral aspect of the C2–C3 zygapophysial joint. The electrode lies in the higher of two
positions required to encompass the third occipital nerve thoroughly. (A block needle overlies the
target zone in case supplementary anesthesia is required.) B: Posteroanterior view of an oblique
insertion. The tip of the electrode lies medial to the lateral margin of the silhouette of the C2–C3
zygapophysial joint. C: Lateral view of a sagittal insertion. The tip of the electrode lies over the
lateral aspect of the C2–C3 zygapophysial joint. The electrode lies in the highest of three positions
required to encompass the third occipital nerve thoroughly. D: Posteroanterior view of a sagittal
insertion. The electrode lies tangential to the C2–C3 zygapophysial joint.

The third occipital nerve wraps around the waist or lower half of the
C2–C3 zygapophysial joint.111 It furnishes articular branches to the joint
from its deep aspect. The location of the third occipital nerve is quite
variable but in a predictable area.57 Most often, it lies along the equator of
the C2–C3 zygapophysial joint, but it can also lie low on the joint, toward
the waist of the C3 articular pillar. Consequently, there is no single target
point for neurotomy. Rather, a target zone has to be coagulated, in order to
accommodate variations in the exact location of the nerve.109
In order to reach the proximal end of the third occipital nerve, the
electrode is inserted along a 30-degree oblique path so that its tip tucks
across the ventrolateral aspect of the joint (see Fig. 102.5). To reach the

5076
more distal segment of the nerve, the electrode is inserted along a sagittal
path so that its tip rests tangential to the lateral aspect of the joint (see Fig.
102.5).
Along each path, the tip of the electrode has to be adjusted into two or
more, higher or lower locations so that the entire target zone is coagulated.
Fewer such adjustments are required if large-gauge (16G) electrodes are
used, but more lesions need to be made if small-gauge electrodes are used.
At each location, the target zone is coagulated by holding the electrode
temperature at 80 to 85°C for 90 seconds.109
This intervention has not been subjected to a placebo-controlled trial
because it is not possible to mask the procedure. Active treatment produces
a patch of anesthesia in the cutaneous territory of the third occipital nerve.
However, the procedure has been benchmarked by an observational study.
That study showed that when patients were selected on the basis of
complete relief of headache following controlled blocks of the third
occipital nerve and when third occipital neurotomy was performed
according to prescribed standards,109 complete relief of headache was
achieved in 88% of patients, for a median duration of some 297 days.172
That relief was associated with restoration of activities of daily living and
no need for other health care. Such results have been corroborated by other
studies,152–154 which included patients with cervicogenic headache but did
not focus explicitly on them. For patients in whom headaches recur, relief
can be reinstated by repeating the neurotomy. By repeating neurotomy as
required, some patients have been able to maintain relief of their headache
for longer than 2 years,172 for up to 5 years,154 and beyond.152
Others who have purported to study cervicogenic headache in controlled
trials have not matched these benchmarks,173–175 but in those studies,
• Patients were selected simply on the basis of clinical criteria.
• Nerves were indiscriminately targeted, without having been subjected
previously to controlled blocks.
• None of the surgical techniques has ever been validated anatomically
or clinically.
So, there was no evidence in these controlled trials that any of the
patients had third occipital headache and no evidence that the technique
used could successfully and thoroughly coagulate the third occipital nerve.

5077
Consequently, these controlled trials do not contribute any evidence
concerning the efficacy or effectiveness of third occipital neurotomy when
performed correctly.
Third occipital neurotomy is associated with distinctive side effects:
notably numbness, ataxia, and dysesthesia.172 Numbness is to be expected
because the third occipital nerve has a cutaneous distribution that is larger
and more constant than that of typical cervical medial branches. Touch-
evoked hypersensitivity and dysesthesia typically resolve spontaneously,
usually within a fortnight, but may last up to 6 weeks. The third occipital
nerve also innervates the semispinalis capitis and contributes substantially
to cervical proprioception and tonic neck reflexes. Therefore, neurotomy is
commonly associated with a mild ataxia. Generally, this ataxia is not
disabling, for patients can rely on visual cues to locate horizontal objects
and thereby stabilize the orientation of their head. No long-term effects
have been reported.
Because of possible problems with ataxia, presumptive bilateral
neurotomy is not recommended in patients with bilateral third occipital
headache. If bilateral neurotomy is indicated, it is recommended that one
side be treated first and the other side be tested with a prognostic block to
test that subsequent neurotomy on this side does not produce disabling
ataxia.171

Sacral Lateral Branch Neurotomy

Sacral lateral branch neurotomy is a procedure devised for the treatment of
sacroiliac pain. It involves coagulating the lateral branches of the S1–S3
dorsal rami where they emerge from their dorsal sacral foramina.
A variety of methods have been used to coagulate these nerves, ranging
from conventional, monopolar electrodes to bipolar electrodes, cooled
electrodes, and special multipronged electrodes. None has emerged as the
preferred method, and outcomes have been less than impressive.
Moreover, the indications for the procedure have not been rigorous.
The most unambiguous indication for lateral branch neurotomy would
be complete relief of pain from controlled, diagnostic blocks of the sacral
lateral branches, but no one has followed this paradigm. Instead, a variety
of other indications have been used.

5078
 One indication has been a positive response to intra-articular blocks of
the sacroiliac joint, in the belief that lateral branch neurotomy should be a
treatment for sacroiliac joint pain. Indeed, a recent Appropriate Use
Criteria listed relief from intra-articular blocks as a prime indication for
lateral branch neurotomy.176 However, this belief is inconsistent with the
available evidence.177 Anesthetizing the lateral branches does not protect
normal volunteers from experimental pain from the sacroiliac joint.178
Consequently, lateral branch neurotomy cannot be a logical treatment for
sacroiliac joint pain, and positive sacroiliac joint blocks cannot be a logical
indication for lateral branch neurotomy.
Anesthetizing the lateral branches protects normal volunteers from
experimental pain from the posterior sacroiliac ligaments.178 Therefore, a
logical indication for lateral branch neurotomy would be sacroiliac
ligament pain, for which the diagnostic test would be controlled blocks of
the sacral lateral branches. However, in that regard, several problems arise.
No one has systematically determined the prevalence of sacroiliac
ligament pain. So, we do not know if this is a common or a rare condition.
No one has determined if the condition occurs in isolation or concurrently
with sacroiliac joint pain. The previously conventional technique, using
single-site blocks, has been shown to be flawed, in that it often fails to
capture the target nerves.179 More accurate is a multisite, multidepth
technique,178 but no one has applied this technique to determine the
prevalence of sacroiliac ligament pain. In principle, single blocks—by any
technique—would be liable to false-positive responses, but no one has
reported using controlled diagnostic blocks of the sacral lateral branches,
and the false-positive rate is not known, either for single blocks or
controlled blocks.
For these various reasons, sacral lateral branch neurotomy lacks a firm
foundation. Although a rationale for lateral branch neurotomy can be
formulated, data consistent with this rationale are few.
Most studies selected patients on the ill-founded basis of positive
responses to one or two intra-articular blocks.180–188 For achieving at least
50% relief of pain, they variously reported success rates of 50% to 80% at
2 or 3 months, reducing to 30% to 60% at 6 and 9 months.
One study selected patients on the basis of an initial intra-articular

5079
block, supplemented by a single lateral branch block.189 It reported 50% of
patients having at least 50% relief at 9 months.
The only study that used lateral branch blocks alone, selected patients
who had at least 75% relief from each of two blocks that were not in any
way controlled.190 At 6 months after lateral branch neurotomy, 27% of
patients had greater than 50% relief of pain, and 18% reported being
totally free of pain. At 9 months, these figures were 52% and 15%. The
proportion of patients who achieved good outcomes at 1 month was nearly
six times greater than that of patients who underwent sham therapy, but the
small sample size prevented demonstrating an absolute statistically
significant difference.
Although the development of sacral lateral branch neurotomy was
inspired by the success of cervical and lumbar medial branch neurotomy,
the outcomes of lateral branch neurotomy have not mirrored those
achieved by medial branch neurotomy. Most studies have reported only
the achievement of 50% relief of pain. No evidence has appeared that such
an outcome is sufficient to reduce the burden of illness.
The one study that most closely adhered to the rationale for lateral
branch neurotomy191 achieved complete relief of pain in only 18% of
patients. The reason for this low yield is not known. There may be
limitations to surgical technique, or it may be that 75% relief from
diagnostic blocks is not a sufficiently rigorous selection criterion. For
medial branch neurotomy, the best outcomes have been achieved after
complete relief of pain following controlled diagnostic blocks.

Discussion
The published evidence shows that of all the neurolytic procedures,
thermal RF neurotomy is the most widely successful in terms of the
diversity of pain problems for which it can be used, its success rate for
achieving complete or near-complete relief of pain, and the duration of
effect than can be achieved, either from a single application or by
repeating the treatment in order to reinstate relief.
The effectiveness of RF neurotomy for trigeminal neuralgia has not
been questioned despite no placebo-controlled trials having been

5080
conducted. Its success rate has been consistently so high, and its effects so
enduring, that it has been exempt the requirement for placebo-controlled
trials.
RF medial branch neurotomy has also been shown to be successful. Of
all treatments for any form of spinal pain, it is the only one that has been
shown to be capable of achieving complete relief of pain accompanied by
restoration of function and eliminating the need for other health care. In
that regard, it is the only treatment for spinal pain that has been shown to
reduce the burden of illness.
However, RF medial branch neurotomy is not a treatment for
nonspecific spinal pain. It is applicable only for pain mediated by one or
more medial branches of the dorsal rami. For the treatment of that
condition, the diagnosis must be rigorously established using controlled
diagnostic blocks, and the treatment must be performed meticulously.
Only under those conditions can optimal outcomes be achieved.
Unfortunately, both in the published literature and in practice, these
conditions are not always met. Taking shortcuts in diagnosis, and
imprecision of surgical technique, decrease the success rate and
effectiveness of medial branch neurotomy, which gives the procedure a
poor reputation. These problems, however, are an indictment of how the
treatment is practiced but not an indictment of its effectiveness.

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134. Cohen SP, Williams KA, Kurihara C, et al. Multicenter, randomized, comparative cost-
effectiveness study comparing 0, 1, and 2 diagnostic medial branch (facet joint nerve) block
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135. Gallagher J, Petriccione di Valdo PL, Wedley JR, et al. Radiofrequency facet joint
denervation in the treatment of low back pain: a prospective controlled double-blind study to
assess its efficacy. Pain Clin 1994;7:193–198.
136. Leclaire R, Fortin L, Lambert R, et al. Radiofrequency facet joint denervation in the treatment
of low back pain: a placebo-controlled clinical trial to assess efficacy. Spine 2001;26:1411–
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137. Dreyfuss P, Baker R, Leclaire R, et al. Radiofrequency facet joint denervation in the treatment
of low back pain: a placebo-controlled clinical trial to assess efficacy. Spine 2002;27:556–
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138. van Kleef M, Barendse GA, Kessels A, et al. Randomized trial of radiofrequency lumbar facet
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139. van Wijk RM, Geurts JW, Wynne HJ, et al. Radiofrequency denervation of lumbar facet joints
in the treatment of chronic low back pain. A randomized, double-blind sham lesion-controlled
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140. van Wijk RM, Geurts JW, Groen GJ. Comments on efficacy of radiofrequency facet
denervation procedures. Pain Med 2012;13:843–845.
141. van Tilburg CW, Stronks DL, Groeneweg JG, et al. Randomised sham-controlled double-
blind multicentre clinical trial to ascertain the effect of percutaneous radiofrequency treatment
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142. Juch JNS, Maas ET, Ostelo RWJG, et al. Effect of radiofrequency denervation on pain
intensity among patients with chronic lowback pain the Mint randomized clinical trials.
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143. Vorobeychik Y, Stojanovic MP, McCormick ZL. Radiofrequency denervation for chronic low
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144. Rimmalapudi V, Buchalter J, Calodney A. Radiofrequency denervation for chronic low back
pain. JAMA 2017;318:2255–2256.
145. Ming-Chih Kao MC, Leong MS, Mackey S. Radiofrequency denervation for chronic low back
pain. JAMA 2017;318:2256.
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147. Tekin I, Mirzai H, Ok G, et al. A comparison of conventional and pulsed radiofrequency
denervation in the treatment of chronic facet joint pain. Clin J Pain 2007;23:235–249.
148. Gofeld M, Jitendra J, Faclier G. Radiofrequency denervation of the lumbar zygapophysial
joints: 10-year prospective audit. Pain Phys 2007;10:291–300.
149. Nath S, Nath CA, Pettersson K. Percutaneous lumbar zygapophysial (facet) joint neurotomy
using radiofrequency current, in the management of chronic low back pain: a randomized
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cervical zygapophysial joint pain: a caution. Neurosurgery 1995;36:732–739.
151. Lord SM, Barnsley L, Wallis B, et al. Percutaneous radiofrequency neurotomy for chronic
cervical zygapophysial joint pain. N Engl J Med 1996;335:1721–1726.
152. McDonald G, Lord SM, Bogduk N. Long-term follow-up of patients treated with cervical
radiofrequency neurotomy for chronic neck pain. Neurosurgery 1999;45:61–68.
153. Barnsley L. Percutaneous radiofrequency neurotomy for chronic neck pain: outcomes in a
series of consecutive patients. Pain Med 2005;6:282–286.
154. MacVicar J, Borowczyk J, MacVicar AM, et al. Cervical medial branch radiofrequency
neurotomy in New Zealand. Pain Med 2012;13:647–654.
155. Engel A, Rappard G, King W, et al; for Standards Division of the International Spine
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of the published data. Pain Med 2016;17:658–669.
156. Royal M, Wienecke G, Movva V, et al. Retrospective study of efficacy of radiofrequency
neurolysis for facet arthropathy. Pain Med 2001;2:249.
157. Shin WR, Kim HI, Shin DG, et al. Radiofrequency neurotomy of cervical medial branches for
chronic cervicobrachialgia. J Korean Med Sci 2006;21:119–125.
158. Wallis BJ, Lord SM, Bogduk N. Resolution of psychological distress of whiplash patients
following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo-
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psychological features in individuals with chronic whiplash symptoms. Pain Phys

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hyperexcitability and improves neck movement in individuals with chronic whiplash. Pain
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pain. Cochrane Database Syst Rev 2003;(1):CD004058. doi:10.1002/14651858.CD004058.
162. Basset K, Sibley LM, Anton H, et al. Percutaneous radio-frequency neurotomy treatment of
chronic cervical pain following whiplash injury: reviewing evidence and needs. Vancouver,
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literature of interventional pain medicine. Reg Anesth Pain Med 2003;28:547–560.
165. Drinka PJ, Jaschob K. Treatment of chronic cervical zygapophysial joint pain [letter]. N Engl
J Med 1997;336:1530.
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Textbook of Medicine. 3rd ed. New York: Oxford University Press; 1996:2979.
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procedures. Pain Med 2008;9:S11–S34.
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172. Govind J, King W, Bailey B, et al. Radiofrequency neurotomy for the treatment of third
occipital headache. J Neurol Neurosurg Psychiat 2003;74:88–93.
173. Haspeslagh SR, van Suijlekom HA, Lame IE, et al. Randomised controlled trial of cervical
radiofrequency lesions as a treatment for cervicogenic headache. BMC Anesthesiol 2006;6:1.
174. Stovner LJ, Kolstad F, Helde G. Radiofrequency denervation of facet joints C2-C6 in
cervicogenic headache: a randomised, double-blind, sham-controlled study. Cephalalgia
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175. van Suijlekom HA, van Kleef M, Barendse GAM, et al. Radiofrequency cervical
zygapophyseal joint neurotomy for cervicogenic headaches: a prospective study of 15
patients. Funct Neurol 1998;13:297–303.
176. MacVicar J, Kreiner DS, Duszynski B, et al. Appropriate use criteria for fluoroscopically
guided diagnostic and therapeutic sacroiliac interventions: results from the spine intervention
society convened multispecialty collaborative. Pain Med 2017;18:2081–2095.
177. Bogduk N. A commentary on appropriate use criteria for sacroiliac pain. Pain Med
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branch blocks to anesthetize the sacroiliac joint complex. Pain Med 2009;10:679–688.
179. Dreyfuss P, Snyder BD, Park K, et al. The ability of single site, single depth sacral lateral
branch blocks to anesthetize the sacroiliac joint complex. Pain Med 2008;9:844–850.
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decision-making for the patients with lumbar zygapophyseal and sacroiliac joint arthropathy. J
Korean Med Sci 2007;22:1048–1054.
182. Speldewinde GC. Outcomes of percutaneous zygapophysial and sacroiliac joint neurotomy in
a community setting. Pain Med 2001;12:209–218.
183. Stelzer W, Aiglesberger M, Stelzer D, et al. Use of cooled radiofrequency lateral branch
neurotomy for the treatment of sacroiliac joint-mediated low back pain: a large case series.
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of chronic pain from sacroiliitis: the first case-series. Pain Pract 2008;8:348–354.
185. Karaman H, Kavak GO, Tüfek A, et al. Cooled radiofrequency application for treatment of
sacroiliac joint pain. Acta Neurochir 2011;153:1461–1468.
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radiofrequency ablation of the lateral branches for sacroiliac joint pain. Clin J Pain
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187. Cohen SP, Hurley RW, Buckenmaier CC, et al. Randomized placebo-controlled study
evaluating lateral branch radiofrequency denervation for sacroiliac joint pain. Anesthesiology
2008;109:279–288.
188. Burnham RS, Yasui Y. An alternate method of radiofrequency neurotomy of the sacroiliac
joint: a pilot study of the effect on pain, function, and satisfaction. Reg Anesth Pain Med
2007;32:12–19.
189. Cohen SP, Abdi S. Lateral branch blocks as a treatment for sacroiliac joint pain: a pilot study.
Reg Anesth Pain Med 2003;28:113–119.
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branch) radiofrequency denervation. Reg Anesth Pain Med 2009;34:206–214.
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398.

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SURGICAL APPROACHES

CHAPTER 103
Surgery of the Peripheral Nervous
System as a Treatment for Pain
JAMES MICHAEL MOSSNER and PARAG G. PATIL

In this chapter, we consider ablative and decompressive surgical

approaches to pain that target the peripheral nervous system. Ablative
procedures interrupt signal flow between pain generators in the periphery
and brain. For example, cutting a peripheral nerve may prevent
transmission of pain-encoding signals from an injured region to the spinal
cord. By contrast, nonablative procedures may relieve pain due to
compression of nerves by adjacent connective tissue.
There are five major categories of pain surgery involving the peripheral
nervous system: peripheral neurectomy, nerve entrapment release, dorsal
rhizotomy and ganglionectomy, sympathectomy, and neurostimulation.
The treatment of trigeminal neuralgia, one of the most prevalent pain
diseases successfully treated with surgery, is presented in Chapter 104.
Ablative procedures aimed at the spinal cord, such as the dorsal root entry
zone operation for brachial plexus avulsion or cordotomy for cancer pain,
are presented in Chapter 105. Neurostimulation procedures, including
dorsal column stimulation, nerve root stimulation, and peripheral
nerve/field stimulation, are presented in Chapter 96.
There are two fundamental approaches to control intractable pain:
attempts to palliate symptoms and attempts to eliminate pain definitively.
Pharmacologic, psychological, physiotherapeutic, neuromodulation, and
neurointerventional approaches each attempt to reduce the severity of pain
symptoms. Surgical approaches have great appeal for their potential to
eliminate pain altogether. In fact, nerve decompressions are among the
most common peripheral nerve surgeries. By contrast, ablative procedures
such as neurectomy and ganglionectomy are notorious for achieving only

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short-term benefits, a reputation that undermines their appeal. In support of
such skepticism, animal research suggests that axotomy alone may be
sufficient to induce pain.1 However, regardless of the perception that
inappropriate patient selection may lead to considerable morbidity, the
experience of some clinicians remains that ablative procedures have the
capacity to relieve pain enduringly and that ablative procedures are useful
therapeutic ventures in properly selected patients.

Peripheral Neurectomy
BASIC CONSIDERATIONS
There are two reasons that a nerve may be cut to eliminate pain. One
reason is to denervate a peripheral pain-producing structure to treat
nociceptive pain. For example, facet rhizotomy denervates the facet joint
as a treatment for axial spine pain. A second reason to cut a nerve is to
remove an abnormal focus of nerve injury (e.g., excision of a neuroma). In
this case, there is some irony in the use of neurectomy to treat pain, as
transection of a somatic nerve may have been the original cause of the
pain. To understand how neurectomy may relieve pain, we must consider
some aspects of the pathophysiology of neuropathic pain.

Pathophysiology of Neuropathic Pain

When sensory nerve fibers are severed, the proximal axons remain in
continuity with cell bodies in the dorsal root ganglion. These axons sprout
and seek Schwann-cell guides. Schwann cells are believed to upregulate
expression of neurotrophic factors, which induce axonal growth.2–5 If the
perineurium of the injured nerve has remained intact, as in the case of
crush or certain thermal injuries, the sprouts may successfully reinnervate
the target tissue. Successful regeneration may also occur when the
transected ends of the nerve are surgically reapproximated (neurorrhaphy).
However, when Schwann-cell guides are not present, the axon sprouts are
unable to reach the target tissue and randomly double back on themselves.
This disordered process of growth ultimately results in a densely packed
cluster of nerve sprouts known as a neuroma.
Weir Mitchell6 brought attention to the problem of painful nerve injury

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after caring for wounded soldiers during the American Civil War. A
century later, Denny-Brown and Kirk2 presented one of the first studies
demonstrating that axotomy can induce behavioral signs of pain in an
animal model. More recent studies have suggested that axotomy of a major
nerve, by itself, may induce hyperalgesia in animals. Although
nontraumatic neuropathies may induce pain in diverse ways, the single
nerve lesion offers a useful model through which to understand the
mechanisms of neuropathic pain.
At least four pathophysiologic mechanisms appear to play a role in
nerve injury pain.
Ectopic generation of action potentials: Although normally silent,
nociceptive afferents may become spontaneously active following nerve
injury, producing action-potential activity in the absence of a stimulus.3
This activity may be experienced as spontaneous pain. In addition to
abnormal signaling in the nerve itself, the activity may sensitize central
neurons, such that inputs from nonnociceptive, tactile afferents produce
pain (allodynia).7
Ectopic excitability: Uninjured nerve trunks are minimally sensitive to
mechanical stimuli. Gentle percussion over a nerve is not painful.
Following injury, however, regenerating fibers may abnormally respond to
mild, mechanical stimuli. Such ectopic mechanical excitability gives rise
to Tinel sign, an electrical sensation in the nerve’s original target
distribution, elicited by mechanical stimulation at the location of
regenerating axons. Furthermore, ectopic excitability to mechanical stimuli
may be accompanied by chemical sensitization. For example, injured
nociceptive axons may become abnormally sensitive to catecholamines.
As a result, the physiologic release of norepinephrine from sympathetic
terminals may induce pain (sympathetically maintained pain [SMP]).4,5
Nervi nervorum: Nerves themselves appear to be innervated by
nociceptive fibers. These nervi nervorum fibers may be sensitized to
mechanical stimuli following nerve injury. Such a mechanism may
explain, for example, the local tenderness and mechanical hyperalgesia of
the ulnar nerve when it is entrapped at the elbow or the local tenderness of
nerves entrapped by scar tissue.8
Ephaptic conduction: Under normal conditions, signals in adjacent

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afferent nerve fibers are insulated from each other. Activity in an injured
nerve fiber may cross to a nearby fiber, through a direct electrical
connection between the two. During such ephaptic transmission, or cross-
talk, a nonnoxious sensory stimulus may evoke activity in nociceptive
fibers and thereby cause pain.
Some of the mechanisms of ectopic generation of action potentials and
ectopic excitability have been described. When an axon is severed, the
axonal transport of sodium channels and other ion channels from the
neuronal cell body to the sensory terminal is interrupted. As a result,
channels may be expressed ectopically in the neuroma formed at the nerve
injury site. Nociceptive fibers in the neuroma thereby become sensitive to
normally nonpainful stimuli, producing pain when these stimuli are
present.9,10 In addition, nerve injury may lead to profound changes in gene
expression, promoting ectopic excitability.11
Other mechanisms may also contribute to neuropathic pain. Although
inflammatory and neuropathic pain syndromes are traditionally considered
separately, immunologic studies have implicated several pathways through
which inflammatory responses may alter nociceptive processing, resulting
in neuropathic pain.12 Evidence supports what may be termed the
wallerian degeneration hypothesis.13 According to this hypothesis,
uninjured nociceptors that are adjacent to nerves undergoing wallerian
degeneration may become spontaneously active and develop sensitivity to
catecholamines, resulting in spontaneous pain and SMP. To the extent that
neuropathic pain results from these mechanisms, peripheral neurectomy
may be expected to worsen pain because the nerve undergoes wallerian
degeneration distal to the site of neurectomy.

Rationale for Neuroma Relocation Surgery

The concept of surgery to remove a neuroma as a treatment of nerve injury
pain is a flawed one. Neuromas arise from nerve fibers proximal to a
region of transection or severe injury, which remain in continuity with
their cell bodies in the dorsal root ganglia. Cutting the nerve at a location
that is proximal to the site of nerve injury to remove the neuroma results in
the formation of a new neuroma at the proximal location. Surgery in which
neuromas are “removed” should therefore be termed neuroma relocation

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surgery.
Not all neuromas are painful. The tissue milieu surrounding the nerve
may determine whether a neuroma becomes painful or remains painless.
The use of peripheral neurectomy as a treatment for painful neuromas is
therefore predicated on the hope that relocation of the neuroma may
convert it from a painful one to a painless one. For example, relocating a
neuroma to a non–pressure-sensitive area may alleviate pain in some
patients. Relocation of neuromas into muscle was first described in 1918.
Since that time, the identification of anatomic locations appropriate for
nerve relocation has improved outcomes substantially.14–22
Thus, an important consideration in peripheral neurectomy is the role of
location in the production of pain. If the location of nerve injury
contributes to pain, then relocating the neuroma to a mechanically
favorable area may be advantageous. However, to the extent that there is
location-independent ectopic generation of action potentials in the
neuroma, neuroma relocation surgery will fail. Additionally, some
investigators have argued that central mechanisms may account for pain in
many nerve injuries.23 In this circumstance, neuroma relocation surgery
may also fail. However, our observations as well as those of other
experienced clinicians suggest that in patients with nerve injury pain,
where anesthetic block of the injured nerve relieves pain, peripheral
neurectomy may provide significant pain relief.

CLINICAL CONSIDERATIONS
Preoperative Evaluation
Clinical scenarios favoring peripheral neurectomy may be broadly divided
into two circumstances: neuropathic pain resulting from nerve injury and
nociceptive pain from a diseased tissue other than nerve. Nerve injury pain
is characterized by numbness, burning, and allodynia. Tinel sign may be
present at the site of a painful neuroma. Candidates for neuroma relocation
surgery should respond to local anesthetic blockade.
Successful anesthetic blockade is an important prerequisite for effective
neuroma relocation surgery. If blockade of the putative, pain-generating
neuroma fails to relieve pain nearly entirely, the rationale for neuroma
relocation surgery is precarious. The decision to operate may be made with

5095
more confidence if more than one block is done. Once candidate nerves
are identified, local anesthetic blocks indicate the level of benefit that can
be obtained following nerve ablation. A successfully applied block should
induce anesthesia in the distribution of each target nerve, but not beyond,
to indicate the specificity of the blockade. Injection of saline or injections
away from the nerve may enhance blockade specificity by identifying
nonspecific responses (e.g., placebo responses).
Findings associated with complex regional pain syndrome (CRPS), such
as edema, hyperalgesia, and trophic changes, also suggest that neurectomy
will not alleviate pain. Notably in such cases, peripheral nerve blockade
typically produces little relief. Patients should be additionally assessed for
hyperalgesia to cooling stimuli. This finding is suggestive of SMP,
discussed in the following text. Finally, local tenderness in combination
with Tinel sign suggests nerve entrapment. In this instance, nerve
decompression would be indicated rather than neurectomy. It is important
to note that even subtle entrapments without significant motor or sensory
loss may induce severe pain.
Even after one has identified a specific nerve as the pain generator, and
one has determined that there are no contraindications to neuroma
relocation surgery, a wait-and-see approach may remain most appropriate.
For example, where injury is relatively recent and the nerve relatively
minor, one may choose to observe. The pain may resolve spontaneously.
Where there is only partial nerve injury with remaining function,
neurectomy may sacrifice function without any assurance that the new
neuroma will be less painful than the old one. In this circumstance, nerve
repair should be considered before performing neuroma relocation surgery.
Nerve repair has the potential to relocate neuromas with the advantage
of restoring neurologic function. The clinician sometimes faces the ironic
situation that to repair an injured nerve, a normal nerve (e.g., sural nerve)
may be sacrificed to provide donor grafts. In effect, nerve repair is, in a
sense, still a neuroma relocation operation—the neuroma is relocated to
the donor nerve. Repair of an injured nerve, when feasible, is generally
preferable to permanent transection. By contrast, if a nerve has already
been completely severed, the risk of relocating the neuroma is low. Thus,
in a case of a well-defined neuroma, when an anesthetic block relieves

5096
pain, surgical neurectomy may be the preferred first line of surgical
therapy.
Careful analysis may lead to rewarding outcomes. The following case
presents the history, preoperative evaluation, and treatment of a patient
with neuropathic pain.
A 44-year-old woman presented with a chief complaint of right vaginal
pain. This problem had been present for 3 years and originated with an
excisional biopsy of a right-sided vaginal ulcer near the introitus. The pain
was always present, but especially disturbing were lightning attacks of
pain that occurred unpredictably several times a day. Examination
disclosed a subtle sensory loss in the right vulvar area. Medication trials
were minimally helpful. An anesthetic block of the right pudendal nerve
led to 50% pain relief. A combined ilioinguinal and genitofemoral nerve
block also led to 50% pain relief. A local anesthetic block of all three
nerves together led to 100% pain relief. As treatment, the right pudendal
nerve was severed distal to the sacral spinous ligament through a
perivulvar approach, and the patient, predictably, had 50% of her pain
relieved. At a separate surgery, the right ilioinguinal and genitofemoral
nerves were severed through a retroperitoneal approach. At 3-year follow-
up, the patient had complete relief. There were no adverse sequelae.
In this case, both lumbosacral neural segments provided innervation to
the painful neuromas. Failure to appreciate this would have led to a less
than satisfactory result. This case underscores the need for complete
blockade of pain during the application of local anesthetic to ensure that all
involved nerves are identified.

Operative Technique
Once peripheral neurectomy has been selected as the treatment of choice,
the primary surgical issue is where to relocate the neuroma. Troublesome
neuromas typically are in areas near joints, scars, and structures that may
tether the nerve. The idea of surgery is to relocate the neuroma to a new
location where tethering does not occur.17 Nerves may be cut back to
locations such that the ends can be placed in healthy, well-vascularized
muscle. Some have also advocated that neuromas be placed in holes in
bone. Placement of a cut nerve into these environments does not change

5097
the fact that the cut ends of the nerve will sprout and that a neuroma will
form. However, with relocation of the neuroma into muscle or bone,
chances are reduced that the new neuroma will be subject to the tension
and shearing forces likely to play a role in pain generation.
Alternatives to neuroma relocation exist. The nerves may be cauterized,
frozen, burned, or injected with toxic chemicals. These options have been
reported to be successful, but their advantages over surgical neurectomy
have not been demonstrated. A surgical procedure where the neurectomy
is done sharply, with limited damage to the surrounding environment of
the nerve, is most appealing from a mechanistic perspective. Damage to
the surrounding tissues, such as necrosis due to phenol injection, may
create a new focus for pain generation.24

INDICATIONS AND OUTCOMES FOR TREATMENT OF

NEUROPATHIC PAIN
Ordinarily, neurectomy should be reserved for those situations in which
nerve decompression is unlikely to provide a satisfactory result and nerve
repair is not possible. Division of major nerves can cause significant motor
deficits, sensory deficits, and pain. Ablation of such nerves as a treatment
of pain should ordinarily be considered only if the nerve is already
divided. Nerve graft repair should be considered as an alternative to repeat
transection. Neurectomy of minor nerves has a role in pain treatment, and
the risk–reward ratio may be favorable.

Amputation Stump Pain

In cases of stump pain, it is worthwhile to examine the patient for tender
neuromas. A prosthetic device, for example, may apply pressure to the
neuroma, causing pain. Surgical relocation of neuromas to more proximal
or protected locations, often in conjunction with nerve wrapping, may
provide significant benefit in these cases.25,26

Intercostal and Intercostobrachial Pain

Chest trauma or thoracotomy may damage intercostal nerves. Shoulder
trauma and axillary node dissection may damage the intercostobrachial
nerve. Motor deficits associated with intercostal and intercostobrachial

5098
neurectomy are clinically insignificant. Hence, neurectomy is usually
without significant drawbacks. This procedure can be safely accomplished
through video-assisted thoracoscopy as well as through an open
procedure.27

Perineal and Inguinal Pain

Injuries to the pudendal, ilioinguinal, iliohypogastric, and genitofemoral
nerves may result in severe pain. These injuries are often due to abdominal
and pelvic surgery, episiotomy, hernia repair, entrapment, or blunt trauma.
For example, the Pfannenstiel transverse incision may injure the
ilioinguinal/iliohypogastric nerves. Groin pain from inguinal
herniorrhaphy is not uncommon. Stulz and Pfeiffer28 reported relief of
pain with neurectomy in 70% (16 of 23) of patients with ilioinguinal and
iliohypogastric neuralgia as a complication of prior surgery. Starling and
Harms29 reported similar rates of success: 89% (17 of 19) for ilioinguinal
neuralgia and 71% (12 of 17) for genitofemoral neuralgia. In the largest
series to date, Amid30 reported 95% improvement in pain among 225
patients. Our own experience supports the use of neurectomy, but the
incidence of long-term favorable outcomes is much more modest.31
Recently, Chen and colleagues32 reported that patients who underwent a
laparoscopic retroperitoneal triple neurectomy for inguinal pain over open
and standard procedures for inguinal herniorrhaphy showed superior
outcomes in terms of postoperative pain scores and recovery time.

Meralgia Paresthetica
Entrapment or injury of the lateral femoral cutaneous nerve, meralgia
paresthetica, may result in pain and dysesthesia in the anterolateral thigh.
In cases where the diagnosis is unclear, local anesthetic blockade may be
helpful. Transection should ordinarily be considered as a backup procedure
when decompression is not feasible and nonsurgical approaches, such as
weight loss, have failed.33 A study comparing neurolysis to neurectomy
for the treatment of meralgia paresthetica found that only 60% of patients
who underwent neurolysis reported being pain free compared to 87.5% of
patients treated with neurectomy.34

5099
Saphenous Neuralgia
Entrapment of the saphenous nerve in the subsartorial canal35 may occur
with or without a history of trauma. Damage to the saphenous nerve may
occur when the saphenous vein is harvested during revascularization
procedures.36 Risk factors associated with the development of saphenous
neuralgia after saphenous vein harvest include younger age, female sex,
diabetes mellitus, higher body mass index, distal-to-proximal dissection of
the saphenous vein, and closure of the leg wound in two layers.37 The
condition is associated with pain (with or without numbness) along the
anterior and medial leg and the dorsum of the foot. Proximal neurectomy
may be used if the nerve has been directly injured. Otherwise, in our
experience, the nerve should be decompressed as the first-line treatment.

Morton’s Neuroma
This condition involves compression of the digital nerve, typically
between the third and fourth tarsal bones. The compression leads to a
swelling of the nerve, which is mistakenly called a neuroma. Patients
present with pain in this region worsened by wearing shoes and walking. If
conservative measures (e.g., orthotics) fail, neurectomy may be offered.
Indeed, this operation is a common procedure for this condition. Johnson
et al.38 reported relief of pain in 67% (22 of 33) of patients, with 6 years
average follow-up, following excision of the plantar interdigital neuroma.
Others have reported surgical success rates of up to 90%.39,40 A recent
consecutive cohort study reported that ultrasound-guided radiofrequency
ablation of Morton’s neuroma provided pain relief in 25 out of 30 patients.
This procedure can be completed on an outpatient basis and is less
invasive than traditional neurectomy.41

General Results of Neurectomy for Neuropathic Pain

What are the predicted results of neurectomy for nerve injury pain? The
question is difficult to answer because the patients undergoing this
treatment are heterogeneous. In addition, measurement of patient outcome
varies greatly among studies with regard to methodologic rigor, length of
follow-up, and technique. As suggested by the studies cited earlier, success
rates vary from modest to high.

5100
 Burchiel and colleagues42 have taken a systematic approach to the
treatment of nerve injury pain, moving the field toward a definition of the
indications for neuroma surgery. In their study, 42 patients with nerve
injury pain were divided into four treatment groups:
• Patients with distal sensory neuromas treated by excision of the
neuroma and implantation of the proximal nerve into muscle or bone
marrow
• Patients with suspected distal sensory neuromas in which the involved
nerve was sectioned proximal to the injury site and implanted into
muscle or bone
• Patients with proximal neuromas-in-continuity of major sensorimotor
nerves treated by neuroplasty, which frees a nerve from adjacent
tissue
• Patients with nerve injuries at points of anatomic entrapment treated
by neuroplasty and transposition
Surgical success (rated as a greater than 50% subjective improvement in
pain levels, subjectively rated pain relief as “good” or “excellent,” and no
postoperative narcotic usage) varied between the groups. In the 40 patients
who received postoperative follow-up care over 2 to 32 months (average
of 11 months), 16 (40%) met these criteria. By group, successful pain
relief was accomplished in 44% (8 of 18) of group 1, 40% (4 of 10) of
group 2, 0% (0 of 5) of group 3, and 57% (4 of 7) of group 4.
After obtaining these results, Burchiel et al.42 attempted to determine
retrospectively the extent to which indicators of nerve injury predicted
surgical success. Such indicators included Tinel sign, hyperalgesia, a
“discrete nerve syndrome,” litigation, and prior procedures. Some
predictors showed promise. For example, a discrete nerve syndrome,
defined as a condition in which a single nerve could account for all the
neurologic findings and pain distribution, tended to predict success.
However, none of the relationships between preoperative diagnostic
variables and treatment success achieved statistical significance at the P <
.05 level. Another prospective study found that employment status,
duration of pain, CRPS, smoking, and improvement with nerve block were
all prognostic factors for surgical management of neuroma pain.43
One can only speculate why the results of this series differ substantially

5101
from those of other series. Perhaps patient selection accounts for
differences, yet Burchiel and colleagues42 appeared to discriminate
patients at high risk for failure. Surgical technique could also play a role,
but there is no evidence on which to base such a statement. In some cases,
neuromas are innervated by more than one nerve. For example, proximal
resection of the superficial radial nerve to treat dorsoradial wrist neuromas
often relieves pain only temporarily. Further inspection reveals that the
lateral antebrachial cutaneous nerve may also innervate these neuromas,
and thus, success may require sectioning this nerve as well.44
Another reason for failure in neuroma relocation surgery may relate to
the discovery that the distal side of a severed nerve may also form a
neuroma at the site of injury. Plexus formation distal to the neurectomy
may allow intact nerve fibers from other nerves to sprout in retrograde
fashion to innervate this distal site. This retrograde sprouting may create a
potentially painful neuroma on the “wrong” side.45 Neuroma relocation
surgery should perhaps attend to neuroma formation on both sides of a
severed nerve.

INDICATIONS AND OUTCOMES FOR TREATMENT OF

NOCICEPTIVE PAIN
Neurectomy may be performed to interrupt the flow of pain signals
through intact nerves from a diseased, pain-generating tissue to the spinal
cord. In these cases, a balance is sought between elimination of input from
the pain-generating tissue and the potential formation of a painful
neuroma. Following neurectomy, regrowth of the transected nerve and
invasion of the diseased tissue by surrounding nerves may result in a return
of pain. In addition, intact and otherwise “normal” nerve fibers may be
sensitized by the release of growth factors in partially denervated tissues.
Progression of the underlying disease process may also enlarge the injured
tissue region, producing pain beyond the region of surgery. In spite of
these considerations, in the following disease processes, neurectomy may
be an effective treatment of nociceptive pain.

Axial Spine Pain

The medial branches of dorsal rami innervate the paraspinal muscles, the

5102
interspinous ligament, and the zygapophyseal (facet) joints. Pain
associated with movement of the lower back, which is relieved by rest and
is not attributable to other spine pathology, may be relieved through
bilateral, percutaneous radiofrequency or chemical ablation of these
branches in the lumbar spine.46,47 A success rate of 85% with mean
duration of relief of 10.5 months was reported by Schofferman and Kine48
through this procedure. In addition, neck pain associated with whiplash
injury may benefit from a similar procedure in the cervical spine.49 The
mechanism of pain relief is thought to relate to denervation of the facet
joint. Because the dorsal ramus innervates several structures, other
mechanisms are possible. Evidence is indeterminate for similar pain of
thoracic origin.
Many experts suggest diagnostic anesthetic blocks of the facets prior to
a facet denervation procedure. Good results are expected only in patients
who get excellent benefit from the blocks. Patients who have axial pain in
addition to radicular symptoms tend not to benefit from facet denervation
procedures alone. Among preexisting symptoms, only paraspinal
tenderness has been shown to predict treatment success, whereas increased
pain with facet loading maneuvers predicts less favorable outcomes.50,51
The procedure is performed percutaneously with radiofrequency heat
lesions. The advantages of this procedure are that it can be done on an
outpatient basis and morbidity is low. The disadvantage is that the
procedure often confers only temporary relief or often no relief at all
regardless of the temporary effects of diagnostic facet blocks. In addition
to continuous, high-temperature radiofrequency medial branch ablation,
pulsed radiofrequency, cryodenervation, and phenol neurolysis have also
been used to provide intermediate to long-term pain relief.
In patients with no prior spine surgery, these procedures have been
reported to provide initial relief for 60% to 70% of patients.36,49,50,52 Rates
are reported to be considerably lower, 20% to 50%, for patients with prior
spine surgery.36,52,53 However, a history of spine surgery is associated
with treatment failure not only for radiofrequency denervation but other
interventions as well, including epidural steroid injection and open
surgery. Our view is that this is a low-morbidity procedure that can
provide effective, albeit impermanent, pain relief for patients with axial

5103
spine pain. Recurrence of pain following denervation can be treated with
repeated neurotomy with comparable efficacy. See Chapter 102 for a
detailed discussion of neurolytic blocks, including radiofrequency
neurolysis.

Extremity Joint Pain

Denervation procedures aim to eliminate pain arising from degenerative
processes in the joint while preserving functions that may be lost after
other forms of joint surgery. Buck-Gramcko54 reported retention of wrist
mobility with substantial reduction of pain in 69% (135 of 195) of patients
following wrist denervation surgery. Wilhelm55 reported success in 90%
of patients with tennis elbow treated by denervation. Dellon et al.56
reported satisfaction in 86% (60 of 70) of patients following partial
denervation surgery for persistent, postoperative knee pain. Pulsed
radiofrequency denervation has also been used to provide relief although
generally with shorter effect when compared to conventional
radiofrequency ablation and limited evidence to support the efficacy of this
approach.57

Pelvic Pain
Neurectomy of the superior hypogastric (presacral) plexus has been
advocated as a treatment for medically refractory pelvic pain. In 1948,
Ingersoll and Meigs58 reported complete relief of primary dysmenorrhea in
81% (72 of 89) of women treated with neurectomy. More recently, with
the development of more effective analgesics, ablative approaches to
pelvic pain have been largely limited to patients with secondary
dysmenorrhea associated with endometriosis. Nezhat et al.59 reported at
least 50% relief from pain in 70% to 85% of patients with various stages of
endometriosis, with 1-year follow-up, following presacral neurectomy
combined with excision and vaporization of endometriotic lesions. Debate
over the proper role of presacral neurectomy has been ongoing for well
over 50 years. Introduction of the biopsychosocial model of chronic pain
has potential to spare many women from surgery.

Cancer Pain

5104
Peripheral neurectomy is infrequently used in the treatment of pain due to
cancer. This is due to the availability of alternative strategies with low
morbidity and higher success rates, such as spinal opiates or percutaneous
radiofrequency cordotomy.60,61 Transecting a peripheral nerve may fail to
relieve pain because of overlapping receptive fields of adjacent nerves or
central plasticity. Sectioning major peripheral nerves results not only in
numbness but also in unacceptable motor loss. Peripheral neurectomies are
rarely indicated in the extremities. However, localized chest or abdominal
wall pain can successfully be treated with intercostal neurectomies.
Alcohol injection, cryoprobe, or radiofrequency lesions provide similar
success to open surgery and lowered morbidity for the treatment of cancer
pain.

Nerve Entrapment Release

BASIC CONSIDERATIONS
Pathophysiology of Nerve Entrapment Pain
Nerve entrapment syndromes result from pressure applied directly to a
nerve, causing pain, paresthesias, or weakness in the sensory distribution
of the nerve.44,62,63 Entrapment commonly develops where peripheral
nerves traverse confined anatomic spaces, rest in superficial locations or in
proximity to joints, or become tethered to adjacent tissues. Structural
factors such as anomalous nerves, cervical ribs, muscles, or connective
tissue bands also may contribute. Repetitive motion, nerve traction due to
joint position, chronic vibration, and high force constitute physical
stressors that increase the risk of symptomatic entrapment.
Although the degree of compression required to cause nerve injury may
vary, axonal degeneration follows pressure in a dose-dependent
relationship.64 Symptoms can arise following a few significant events or
after a longer period of repetitive mild insults. The time course and force
of injury are just two of the prognostic considerations. The length of the
affected nerve region as well as the presence and severity of nerve
ischemia are important factors in the development of symptomatic nerve
entrapment. Finally, nerves become more vulnerable to injury in the
presence of concurrent systemic metabolic disease, and nerves lose their

5105
regenerative capacity with age.
Several pathophysiologic mechanisms have been proposed to explain
pain associated with peripheral nerve entrapment at the cellular level.
Evidence for these mechanisms arises from studies of animal models.64–66
Following local nerve compression, internodes along myelinated fibers
distort in shape. Demyelination appears earliest in the segment nearest to
the point of compression.67,68 Eventually, segmental demyelination leads
to diffuse demyelination and, ultimately, axonal degradation. Compressive
injury usually affects larger, more peripherally located myelinated nerves
as opposed to smaller or unmyelinated fibers.
Nerve ischemia may also play an important role in nerve entrapment
pain syndromes. Focal pressures of 20 to 30 mm Hg may impede venous
blood flow, whereas higher pressures may reduce arterial supply.69,70
Within 4 hours of extraneural compression, increasing permeability of the
blood–nerve barrier leads to development of subperineurial edema.71–74 As
there is no lymphatic drainage of the endoneurial space, sustained
intraneural pressure elevations persist for at least 24 hours after
compressive forces are removed. Following such injury, reactive
inflammation, fibrin deposition, and proliferation of endoneurial
fibroblasts and capillary endothelial cells lead to intraneural fibrosis of
perineurial and epineurial tissues.
Ischemia does not appear to play a role in the initial demyelination
associated with acute compressive injury.75,76 Rather, nodes of Ranvier
adjacent to the point of compression are outwardly displaced and disrupt
the myelin sheath. Segmental demyelination follows, stemming from these
sites of myelin invagination.77,78 Disruption of anterograde axoplasmic
flow of vital nutrient proteins reduces terminal membrane excitability.
Long-standing ischemia thereby results in replacement of funicular
contents with fibrotic tissue, producing derangements in electrical
conductivity.79

Nerve Entrapment and Systemic Disease

Several endocrine and rheumatologic diseases show an association with
increased risk for nerve entrapment. Approximately 15% of upper
extremity nerve entrapment patients have diabetes. This may result from

5106
an increased association of peripheral neuropathies with entrapment. Both
hypo- and hyperthyroidism have been shown to pose an increased risk for
nerve entrapment, which is thought to result from glycogen deposition in
Schwann cells.80 Up to 30% of acromegalics are diagnosed with nerve
entrapment syndromes, which often resolve with treatment of the
underlying acromegaly.81,82 Obesity and pregnancy have well-documented
associations with entrapment syndromes, with as many as two-thirds of
pregnant women experiencing temporary symptoms.83 Rheumatoid
arthritis is also thought to contribute to entrapment in anatomic locations
where synovial overgrowth can produce compression of a nerve. There is
an estimated 45% incidence of entrapment neuropathy in rheumatoid
arthritis patients.84,85 Amyloidosis, carcinomatosis, gout,
mucopolysaccharide storage diseases, and polymyalgia rheumatica are all
suspected to pose an increased risk for exacerbation of nerve entrapment.

CLINICAL CONSIDERATIONS
Preoperative Evaluation
Clinical findings: Patients suffering from nerve entrapment syndromes
present with pain, paresthesias, or motor weakness along a specific nerve
distribution. Nocturnal pain, either sharp or burning, classically develops
before the onset of daytime or persistent symptoms. Muscular changes,
such as atrophy or fasciculation, as well as sensory alterations, such as
altered two-point discrimination or temperature sensation, can occur in
advanced cases. Specific symptoms result from the location and severity of
compression.
On physical examination, Tinel sign may be present. Tinel sign is an
electric radiating sensation in the distribution of the nerve, produced by
percussion over the nerve. Tinel sign represents ectopic excitability, a
hallmark of nerve entrapment, and may be accompanied by local
tenderness. Provocative maneuvers may reproduce or exacerbate
symptoms and have significantly positive predictive value in the diagnosis
of entrapment syndromes.
In many cases, diagnosis of a specific entrapment syndrome may be
difficult to make. Compensation of one muscle group by another may
create uncertainty in identifying etiology of the entrapment. Furthermore,

5107
entrapment syndromes may be accompanied by concurrent radiculopathy,
producing synergistic pain, thereby adding to the diagnostic challenge.86 In
addition, pain associated with entrapment syndromes may not be well
localized. For example, radial nerve entrapment may present with global
arm pain. Finally, results of electrodiagnostic studies may be normal in
some cases, further increasing the diagnostic dilemma.
Electrodiagnostic studies: Physical findings may be supported by
electrodiagnostic studies. Nerve conduction studies (NCS) measure action
potentials along axons, whereas electromyography studies (EMG) measure
muscle fiber activity. In sensory NCS, a stimulus is applied to the nerve
and a sensory nerve action potential (SNAP) is measured at various distal
points along the nerve. Alterations in axon number, diameter, myelination,
or temperature all affect the magnitude and temporal profile of the SNAP.
In motor NCS, a stimulus is applied to the nerve and a compound motor
action potential (CMAP) is measured from the innervated muscle. Changes
in conduction velocity, amplitude of CMAP, and distal motor latency
suggest that conduction inhibition exists between the point of initial
stimulation and the site of recording. Needle EMG examines the
spontaneous electrical activity of individual muscle fibers resulting from
denervation, reinnervation, or acute muscle injury.
These studies aid in the differentiation of peripheral nerve entrapments
from brachial plexopathy and radiculopathy by defining the nature and
extent of neurologic dysfunction. For example, although NCS cannot be
performed in structures like the brachial plexus due to an inability to
record and stimulate across the region of compression, a plexus lesion
would be expected to affect the function of multiple peripheral nerves. In
entrapment neuropathy, large myelinated sensory fibers are typically
affected before motor fibers. Hence, NCS are most often effective earlier
in the disease than motor conduction studies (ulnar compression at the
elbow is a notable exception to this rule). Entrapment is represented by
abnormal recordings of evoked SNAPs along a short nerve segment.
Prolonged latency or reduced motor conduction velocity is also indicative
of injury, although they are less sensitive measures. Fibrillation seen on
EMG occurs as a result of wallerian degeneration of distal nerve segments
and suggests advanced entrapment. In general, a combination of studies

5108
and measurement points yields the best information with which to form a
diagnosis.
Comparison among the nerves of interest and a nearby unaffected nerve
is often more accurate than comparison of a nerve with normal reference
values. Cooler temperature, increasing age, and patient size all serve to
prolong sensory latencies, confounding reference values. As a result, and
to avoid such confounding factors, it is common to perform sensory
latency comparisons at as many as three sites (median-ulnar midpalmar,
median-ulnar ring finger, and median-radial thumb) in the diagnosis of
carpal tunnel syndrome (CTS).87 Although the greater number of studies
increases the likelihood of false-positive results,88 summation of the
latencies of these three studies has proven to be the most sensitive and
specific test for CTS.89
Following entrapment release, it is notable that clinical improvement
may not correlate reliably with electrodiagnostic studies. However, in
patients with persistent symptoms following treatment, comparison with
pretreatment studies may be helpful. If earlier studies are unavailable, a
series of postoperative studies over several months should be obtained.
Imaging studies: Developments in ultrasonography and magnetic
resonance imaging (MRI) have resulted in a potentially expanded role for
imaging in the diagnosis of entrapment neuropathies. Ultrasonography
now offers the highest available resolution for visualizing the location of
entrapment (Fig. 103.1). However, ultrasound is unable to show pathologic
changes within nerves. In contrast, signal and configuration characteristics
seen in chronically compressed or tethered peripheral nerves have been
well characterized by MRI (Fig. 103.2). On MRI, indicators for nerve
abnormality include focal enlargement, T2 hyperintensity, and an
indistinguishable or nonuniform fascicular pattern. In addition, MRI
simultaneously visualizes muscular alterations due to atrophy and
neurogenic edema.

5109
FIGURE 103.1 Series of transverse 17.5 MHz sonography images obtained from proximal to
distal over palmar cutaneous branch of median nerve (MN) in 35-year-old healthy man with
corresponding diagrams. Relationships of palmar cutaneous branch of MN (thin arrows) with MN
(thick arrows), flexor carpi radialis tendon (curved arrow in A, C, E, and G; fcr in B, D, F, and H),
and antebrachial fascia (arrowheads, E–H) are shown. A,B: Palmar cutaneous branch of MN
detaches from MN as one of its most radial fascicles. C,D: Palmar cutaneous branch of MN
gradually deflects to approach flexor carpi radialis tendon. E,F: Palmar cutaneous branch of MN
runs slightly deep in relation to antebrachial fascia. G,H: Palmar cutaneous branch of MN lies
adjacent to flexor carpi radialis tendon after piercing fascia. (From Tagliafico A, Pugliese F,
Bianchi S, et al. High-resolution sonography of the palmar cutaneous branch of the median nerve.
Am J Roentgen 2008;191[1]:107–114. Reprinted with permission from the American Journal of

5110
Roentgenology.)

FIGURE 103.2 T2-weighted gradient echo images at the distal part of the distal radioulnar joint
level (DRUJ) (level 1), at the level of the pisiform (level 2), and at the level of the hook of the
hamate (level 3) in three different stages of idio pathic carpal tunnel syndrome. Solid arrow
indicates the cross section of the median nerve. Upper part represents the dorsal side, and the
right-hand side represents the ulnar side. H, hook of the hamate; P, pisiform bone. A–C: Extreme
stage. Enlargement and high signal intensity of the flattened median nerve are seen at level 1, and
enlargement of the median nerve at levels 2 and 3. Palmar bowing of the transverse carpal ligament
(TCL) is evident. D–F: Moderate stage. Enlargement and high signal intensity of the median nerve
are seen at level 2. They are slightly appreciated at level 3 and still not seen at level 1. Palmar
bowing of the TCL is well appreciated. G–I: Normal wrist. Enlargement of the median nerve is not
seen at any level. Isointensity of the nerve to the hypothenar muscle is seen throughout the cross
sections. Palmar bowing of the TCL is not seen. (Reprinted from Uchiyama S, Itsubo T, Yasutomi
T, et al. Quantitative MRI of the wrist and nerve conduction studies in patients with idiopathic
carpal tunnel syndrome. J Neurol Neurosurg Psych 2005;76[8]:1103–1108, with permission from
BMJ Publishing Group Ltd.)

Specific MRI findings have been correlated with clinical findings,

electrodiagnostic findings, and postoperative outcomes for several nerve
entrapment syndromes.90–93 With current technology, MRI may be a
useful adjunct in the diagnosis of entrapment. Specific indications for MRI
may include ulnar entrapment, entrapment in the presence of superimposed
neuropathy, entrapment where other tests are equivocal, and postoperative
evaluation of entrapment.94 The value of MRI imaging in the setting of
uncommon entrapments is less clear.

5111
Operative Technique
Substantial experimental evidence supports three treatments of peripheral
nerve entrapment: splinting, local corticosteroid injection, and surgical
release. Splinting reduces the offending stimulus through postural
correction and reduction of repetitive injury, thereby decreasing reactive
inflammation. Local corticosteroid injections have been shown to be
helpful in mild cases. Surgical release of anatomic compression is the
mainstay of treatment in more advanced cases of peripheral nerve
entrapment.95
In general, operative release of entrapment can be quite rewarding, as
the risks of surgery are typically low and pain improvement is often
dramatic. Avoidance of additional trauma to the compressed nerve is of
great importance to surgical outcome. Occasionally, unexpected sources of
entrapment may be found during surgical exposure, such as cysts, soft
tissue masses, and bony prominences. Choices of surgical approach and
operative technique are based largely on individual surgeon preferences.96
Rates of success and complications vary with the location of entrapment
and the etiology of pain.

INDICATIONS AND OUTCOMES

Entrapments of the Median Nerve
Carpal tunnel syndrome: CTS results from compression of the median
nerve between bones of the wrist and the flexor retinaculum. CTS is the
most common nerve compression syndrome, with an annual incidence of
150 per 100,000 population and a 2:1 female predominance.97,98 Patients
with CTS present with pain along the radial half of the hand, particularly at
night, and weakness of median innervated muscles. Phalen’s sign—
recreation of pain through complete wrist flexion for 30 to 60 seconds—is
a sensitive and specific marker of mild to moderate CTS.99,100
Electrodiagnostic studies typically demonstrate decreased median-nerve
conduction velocity at the wrist. Imaging findings on MRI, when
performed, may demonstrate increased signal intensity in the nerve, volar
bowing of the flexor retinaculum, and flattening of the median nerve at the
level of the hamate.101
Initial therapy includes splinting, activity modification, and nonsteroidal

5112
anti-inflammatory medications for mild disease. Corticosteroid injections
offer nearly a 70% positive response initially, although eventual recurrence
of symptoms is high.102
Surgical decompression of the carpal tunnel is indicated in cases that
have failed conservative management or in cases with severe or rapid
onset of symptoms. Some 80% of patients achieve excellent pain relief
with surgery, whereas another 10% achieve partial relief; less than 1% of
patients experience worsening of their pain symptoms. For patients with
motor weakness, similar results have been reported with 84% of patients
returning to baseline function and another 9% experiencing some
improvement.100,103–105 Early surgery in patients with ongoing pain has
been associated with improved resolution of symptoms.
Incomplete decompression of the nerve is seen in the majority of cases
in which pain relief is incomplete, absent, or transient. Another cause of
recurrent pain includes postoperative fibrosis. Failure to appreciate the
path of the recurrent motor (thenar) branch of the nerve can result in
postoperative weakness following release. Injury to the palmar cutaneous
branch can result in postoperative pain in the wrist and proximal thenar
eminence.106,107 A 2010 review attempted to identify optimal outcome
prognostic factors for patients undergoing carpal tunnel release. They
discovered that having comorbid conditions such as diabetes, poor health
status, thoracic outlet syndrome (TOS), double crush, alcohol, and
smoking led to a worse prognosis. However, they were unable to identify
any positive prognostic indicators that would predict an optimal outcome
in patients with CTS undergoing carpal tunnel release.108
Anterior interosseus syndrome: Anterior interosseus syndrome results
from isolated injury or entrapment of this largely motor branch of the
median nerve.109 The nerve arises distal to the medial epicondyle and is
vulnerable to injury in supracondylar and forearm fractures.110–112 In
severe cases, there may be weakness of flexor pollicis longus, flexor
digitorum profundus to the index finger, and pronator quadratus.
Patients with anterior interosseus syndrome may present with a
characteristic pinch as compensation for weakness in the long flexors of
the index finger and thumb. The condition may also present with pain in
the forearm associated with tenderness in the proximal volar forearm.

5113
EMG may confirm changes associated with muscular denervation.
Surgical exploration with neuroplasty is most commonly performed for
patients whose pain does not respond to anti-inflammatory medications or
avoidance of repetitive pronation/supination activity.113–117
Entrapment by the ligament of Struthers: Struthers’ ligament can
cause compression of the median nerve, brachial artery, or brachial vein as
they pass beneath it, proximal to the medial epicondyle. A variant bony
spicule (supracondylar process) arising from the humerus at this level can
place the nerve at risk for entrapment.118 A rare disorder, this pathology
can potentially be mistaken for CTS.119 Motor weakness of the pronator
teres, flexor carpi radialis, and flexor digitorum profundus (to the first two
digits), although not always present, indicate a point of compression
proximal to the carpal tunnel. Release of the ligament and excision of the
supracondylar process typically provides pain relief.
Pronator syndrome: Pronator syndrome presents as a vague, aching
pain in the volar aspect of the elbow and forearm that is exacerbated by
activities involving grasping or pronation of the forearm.120 On physical
examination, tenderness can usually be elicited by deep palpation over the
pronator teres. Compression occurs at the lacertus fibrosus, within the
muscle between the two heads of pronator teres, or beneath the flexor
superficialis tendon at its origin. Avoiding maneuvers that exacerbate the
pain and intra-muscular injection of corticosteroids may be attempted prior
to surgical release.

Entrapments of the Ulnar Nerve

Ulnar nerve entrapment at the elbow: Ulnar nerve entrapment at the
elbow (UNEE) is the second most common peripheral nerve entrapment
syndrome after CTS. At the elbow, the ulnar nerve is bounded medially
and anteriorly by the medial epicondyle and laterally by the olecranon. A
dense fascial layer overlies this space, forming the cubital tunnel.
Entrapment may occur at the cubital tunnel, in the epicondylar groove,
beneath the arcade of Struthers, or at the medial intermuscular septum.121
Antecedent trauma, inflammatory change, and mass lesions increase the
risk of UNEE. Subluxation of a hypermobile ulnar nerve over the medial
epicondyle may lead to traumatic injury. An anomalous and potentially

5114
compressive anconeus epitrochlearis muscle may be found in up to 30% of
patients.122–124
UNEE typically presents insidiously with paresthesias in the ulnar
distribution of the forearm, wrist, and hand. Muscle weakness leads to
impaired grip and clumsiness in the hand and, in more severe cases,
atrophy of intrinsic hand muscles. Tinel sign and the elbow flexion-
pressure test, which is done with manual compression of the ulnar nerve
just proximal to the cubital tunnel for 30 seconds, offer significant
sensitivity and specificity for UNEE.125,126 Electrodiagnostic studies may
demonstrate reduced sensory and motor conduction velocity across the
elbow.
The optimal surgical technique for entrapment release in UNEE has not
been established. Options include transposition of the nerve and in situ
decompression. For transposition, the ulnar nerve is displaced
anterolaterally in order to shorten its course around the medial epicondyle.
Transposition may be subcutaneous, intramuscular, or submuscular, with
respect to the flexor-pronator muscle mass.127–135 Among the larger case
series, successful surgical results of 90% have been reported regardless of
technique.136–140 Many surgeons favor in situ decompression as an initial
surgical treatment, particularly when patients have milder symptoms and
isolated compression at only one site.141–145
Traumatic etiology, chronic symptoms, absence of sensory potentials,
and severe muscular weakness are among the indicators of poor prognosis
for surgical outcome. Pain symptoms more often resolve, whereas motor
symptoms may only partially improve, after surgery. Persistent pain
following ulnar nerve decompression at the elbow may be due to injury of
the medial antebrachial cutaneous nerve.
Ulnar nerve entrapment at the wrist: The ulnar nerve and artery
course through Guyon’s canal and may become entrapped there.146 This
canal is bounded by the volar and transverse carpal ligaments and palmaris
brevis muscle, with the pisiform bone proximally and medially and the
hook of the hamate laterally and distally. Common causes of entrapment
include local masses, such as ganglion formation, lipomas, and uremic
tumoral calcinosis, or anatomic variants, such as the presence of abductor
digit minimi within the canal.147 Evaluation is typically based on physical

5115
examination and electrodiagnostic studies. MRI, when a dedicated wrist
coil is utilized, offers noninvasive visualization of Guyon’s canal.148
Surgical decompression involves unroofing of the canal and removal of
any masses.149,150

Entrapments of the Radial Nerve

Compression neuropathy of the radial nerve occurs at the radial tunnel, a
5-cm space extending from the capitulum of the humerus to the distal edge
of the supinator muscle. It is bounded anteromedially by the brachialis
muscle, anterolaterally by brachioradialis and extensor carpi radialis
brevis, and posteriorly by the capitulum. Just distal to the lateral
epicondyle, the radial nerve divides into a purely sensory superficial
branch and a deep branch, the posterior interosseous nerve.
Whereas the superficial branch passes superior to the supinator muscle,
the posterior interosseous nerve courses in a plane between the two heads
of the supinator muscle as they both continue into the forearm. Potential
sources of compression at this level include the fibrous bands that anchor
the radial nerve to the elbow, the recurrent radial artery and its associated
vessels and branches (collectively known as the leash of Henry), and the
arcade of Frohse at the fibrous origin of the supinator and other
muscles.149,151–153
Radial tunnel syndrome and posterior interosseous nerve
syndrome: Classically, there are two distinct clinical syndromes involving
this pathology—one primarily involving pain, and the other, motor
dysfunction. Radial tunnel syndrome itself is a frequently cited, yet
somewhat controversial diagnosis, as some argue against its existence. It
consists of pain symptoms including deep aching pain, often worse at
night, in the extensor muscle mass at the lateral elbow. On physical
examination, several particular maneuvers are suggestive of this diagnosis:
(1) reproduction of pain by resisting extension of the third digit, with the
elbow and wrist in full extension; (2) tenderness to palpation over the entry
of the posterior interosseous nerve into the supinator muscle,
approximately 5 cm distal to the radial head; and (3) reproduction of pain
with the application of a tourniquet at this level.154–157
In contrast to radial tunnel syndrome, posterior interosseous nerve

5116
syndrome is defined primarily by motor symptoms, including progressive
weakness of the wrist and digit extensor muscle group. Due to the
relatively distal point of compression, innervation to the brachioradialis,
extensor carpi radialis muscles, and supinator are typically unaffected.
Weakness in wrist extension is incomplete, such that there is radial
deviation. Pain, when present, is secondary in this constellation of
symptoms.
Development of this entrapment syndrome is associated with repetitive
forceful movements involving elbow extension and forearm pronation and
supination.158 Mass lesions, elbow dislocation, vascular malformations,
and synovial inflammation are other potential etiologies of compression,
and MRI or ultrasound may be useful in the identification of compression.
Electrodiagnostic studies are of limited utility for most patients. Hence, the
diagnosis is typically clinical.
Operative release of entrapment includes an exploration of all the
branches of the radial nerve, such that the posterior interosseous branch
can be fully liberated.159 Few large case series have been analyzed, and
reported outcomes vary in the region of 70%. In some series, however,
improved functional outcomes have been reported in over 90% of treated
patients.160–162
Superficial sensory branch entrapment: Entrapment of the superficial
sensory branch of the radial nerve can occur through externally
compressive apparel such as watchbands. Chronic intermittent
compression tends to cause numbness and dysesthesias over the dorsal
surface of the hand, whereas blunt injury at this location typically causes
highly refractory pain. Operative neuroplasty has yielded significant
improvement of symptoms in 74% to 86% of patients.163–165 Of note,
superficial sensory branch entrapment may be associated with De
Quervain’s tenosynovitis, and release of the extensor compartment is
sometimes performed in combination with neuroplasty.

Entrapment of the Suprascapular Nerve

Suprascapular nerve entrapment presents with shoulder pain along the
border of the trapezius muscle and often denervation of the associated
musculature.166–169 On physical examination, it is exacerbated with

5117
abduction and external rotation of the arm. The suprascapular nerve passes
through the suprascapular notch and beneath the suprascapular ligament
before entering the supraspinatus fossa.170 Compression at the
suprascapular ligament is common, and thus, a palsy involving both
supraspinatus and infraspinatus is more frequently seen than an isolated
infraspinatus denervation on EMG. History of trauma such as shoulder
dislocation or scapular fracture is usually present. When this is absent,
suprascapular ligament compression, tumor, ganglion, or Parsonage-
Turner neuritis should be considered. Reported pain relief and strength
increase after surgery have been excellent, with improvement in over 90%
of patients.168,169,171–174 Early surgical treatment appears to yield better
results than a delayed operation.175 This is thought to primarily to prevent
the progression of nerve injury as well as muscle atrophy; however, a true
association between nerve injury and muscle atrophy reversibility and
latency from symptom onset to treatment has yet to be shown.
Additionally, the approach to decompression of the suprascapular nerve is
still hotly debated among physicians.176

Thoracic Outlet Syndrome

The term “thoracic outlet syndrome” (TOS) was coined by Peet177 to
describe compression at the thoracic inlet of the neurovascular bundle
composed of the brachial plexus, subclavian vein, and subclavian artery.
TOS is most commonly neurogenic in origin. In TOS, unlike other upper
extremity entrapments, NCS across the putative entrapment site are not
feasible. The diagnosis is therefore typically based on clinical criteria.
TOS has been subdivided into three syndromic zones, according to
likelihood of entrapment of the brachial plexus, subclavian artery, and
subclavian veins. Anterior scalene syndrome occurs with brachial plexus
or subclavian artery compression in the interscalene triangle.
Costoclavicular syndrome occurs with compression of any nearby
structures in the space between the clavicle and the first rib.
Retropectoralis minor syndrome can involve any adjacent structure as
well, and compression occurs at the attachment site of pectoralis minor at
the coracoid process (the subcoracoid tunnel).178–181
In cases of pure peripheral nerve compression, insidious onset of pain

5118
and paresthesias in the neck, shoulder, arm, or hand is typical, whereas
motor weakness occurs in just 10% of patients. Nearly 90% of cases
involve the ulnar nerve distribution.182 Symptoms may be reproduced
when assuming a spear-throwing position or with downward pressure on
the shoulder. Tenderness (with or without Tinel sign) over the anterior
scalene muscle in the supraclavicular fossa may also be present.
Diagnosis can be aided by imaging and electrodiagnostic studies. In
particular, a radiograph demonstrating anomalous bony findings, such as a
cervical rib, in the presence of corresponding symptoms is highly
predictive of good surgical outcome. Comparing MRIs of the thoracic
outlet in the standard anatomic position and following hyperabduction and
external rotation of the arm may reveal significant narrowing of the
costoclavicular space in patients with TOS compared to normal healthy
subjects.179
With careful attention to patient selection and surgical technique, good
results have been reported with surgical management. Surgery can involve
first rib resection, anterior scalenectomy, resection of the costoclavicular
ligament, or neuroplasty, depending on suspected pathology.183 The
majority of surgeons employ a transaxillary or supraclavicular approach.
In general, immediate pain relief with surgery is good, although results
often deteriorate over time. Numerous outcome studies for the
transaxillary approach report greater than 90% of patients enjoy initial
symptomatic relief. However, long-term follow-up has revealed that less
than 50% of patients sustain relief at 5 years, and less than 10% of patients
have relief persisting at 20 years.181,182,184 Although reported in fewer
numbers and with shorter follow-up, outcomes for the supraclavicular
approach appear to be equally good in terms of initial results.185,186
Complications of surgery for TOS are unfortunately common and include
vascular injury, brachial plexus injury, and thoracic wall injury.187

Entrapments of the Lower Extremities

Of the entrapment syndromes seen in the lower extremities, meralgia
paresthetica (symptoms along the lateral femoral cutaneous nerve) is the
most common. Inciting factors are many, including trauma, weight gain,
and clothing. Indeed, trauma is the foremost cause of peripheral nerve

5119
injury in the lower extremities, particularly around the pelvic, inguinal,
and ankle regions, often involving the femoral, obturator, ilioinguinal,
iliohypogastric, genitofemoral, and posterior tibial nerves. Described
chronic compressive syndromes include entrapment of the lateral femoral
cutaneous, sciatic, saphenous, posterior tibial, common peroneal, deep
peroneal, and plantar digital nerves. Results from surgical management of
meralgia paresthetica and Morton’s neuroma (of a plantar digital nerve)
are discussed with other pathologies treated by neurectomy and will be
omitted here.
Sciatic nerve entrapment: The posterior L4–S3 sacral plexus nerve
roots typically give rise to the sciatic nerve, which travels anterior to the
piriformis muscle before passing beneath its inferior border to exit the
pelvis through the greater sciatic foramen posterior to the piriformis
muscle, along with the superior and inferior gluteal vessels and nerves.
When the sciatic nerve instead travels above or even through the piriformis
muscle, a syndrome of gluteal region pain, weakness in hip abduction
resulting in a lurching gait, and tenderness to palpation just lateral to the
greater sciatic notch can be induced.188 Weakness in knee flexion in the
absence of paraspinous muscle weakness can be suggestive of this
peripheral injury as well, and there is often discrete tenderness between the
greater trochanter and ischium.
This entrapment syndrome is six times more common in women than in
men and often associated with repetitive trauma such as horseback riding,
muscular hypertrophy or ossification, or with iatrogenic injury to the
sciatic nerve.189 It can closely mimic the sciatica caused by lumbar disk
herniation or spinal stenosis, and MRI is particularly helpful in
determining the likelihood of a peripheral nerve entrapment in relation to
the far more common spinal etiologies. Electrodiagnostic tests are very
difficult to perform reliably in this region and are generally of little utility.
Focal tenderness directly over the piriformis muscle, together with normal
MRI of lumbar spine, is suggestive of sciatic nerve entrapment.
Surgical management involves sectioning of the overlying piriformis
muscle and has provided excellent relief in a limited number of reported
cases.190,191 A feared complication of this procedure is complete
sectioning of one of the associated gluteal vessels, which can retract into

5120
the pelvis, necessitating laparotomy for hemostasis.192 There have been
case reports of spontaneous entrapment neuropathies involving the distal
portions of the sciatic nerve in the thigh.193,194 Endoscopic release of the
piriformis muscle has also been shown to be an effective approach to
improving pain symptoms for patients with sciatic nerve entrapment.195
Saphenous nerve entrapment: Iatrogenic saphenous nerve injury is
commonly a result of saphenous vein harvesting. A similar syndrome that
also presents as dysesthesias and pain involving the medial aspect of the
knee and anterior tibial region has been treated successfully with surgical
release in the subsartorial (Hunter’s) canal.35,196 A fascial band between
the abductor magnus and vastus medialis muscles is the offending factor,
and pain can typically be elicited on examination with palpation over the
canal.
Tibial nerve entrapment: Tibial nerve entrapment at the popliteal
fossa results from compression by the tendinous arch of the origin of the
soleus muscle as well as from nerve tumors, Baker’s cyst, and trauma. As
it crosses medially in the popliteal fossa, the tibial nerve travels
superficially to the popliteus muscle while passing under the tendinous
arch of the soleus muscle before entering the space between the heads of
the gastrocnemius and plantaris muscles.197,198
Symptoms of tarsal tunnel syndrome result from compression of the
posterior tibial nerve at the medial malleolus. The tarsal tunnel itself refers
to the deep posterior compartments of the distal leg as they pass beneath
the flexor retinaculum, which is formed from the superficial and deep
aponeuroses of the leg.199 Symptoms typically include pain and
dysesthesias involving the plantar surface of the foot and sometimes the
heel, depending on whether the posterior tibial nerve trifurcates and gives
rise to the medial calcaneus sensory branch proximal to the point of
compression. Tinel sign over the flexor retinaculum is quite sensitive and
specific in the diagnosis of entrapment, particularly when combined with
the dorsiflexion–eversion maneuver.200 In fact, a recent study in 2012
found that a positive Tinel sign over the tibial nerve at the tarsal tunnel in a
diabetic patient with chronic nerve condition at the aforementioned
location predicts significant pain relief and improvement in plantar
sensibility.201 Both MRI and electrodiagnostic studies are extremely

5121
helpful in confirming and assessing severity of the pathology, particularly
in recurrent cases and in those rare instances refractory to conservative
management.202–206 The differential diagnosis is wide and includes such
common etiologies as CRPS, plantar fasciitis, and Achilles tendonitis.
Surgical sectioning of the flexor retinaculum and release of the nerve
has demonstrated only moderate success, perhaps in part due to the success
of conservative management in such a large proportion of cases.207–209
Pfeiffer and Cracchiolo210 reported 44% of patients received significant
improvement after decompression, and two subsequent studies showed
similar overall benefit. Sammarco and Chang211 later reported
significantly better surgical outcomes in patients with duration of
symptoms lasting less than 1 year, compared with disease present for
greater than 1 year. Still, Turan et al.212 demonstrated that surgical
management is still of benefit in those with long-standing symptoms,
providing excellent results in 61% of patients who experienced symptoms
for more than 5 years.
Peroneal nerve entrapment: Once the sciatic nerve reaches the
popliteal fossa, it gives rise to the common peroneal nerve, which then
wraps around the fibular head and passes into the peroneal tunnel
alongside the peroneus longus tendon. There, it trifurcates, giving off
superficial and deep peroneal nerve branches as well as a sensory branch
to the tibiofibular joint and knee.213 Entrapment syndromes typically arise
due to compression in the knee (due to fatty tissue deposition or Baker’s
cyst) or at the peroneal tunnel, but the superficial and deep branches can be
compressed at the fascial exit of the superficial branch over the
anterolateral aspect of the lower shin214 and at the anterior tarsal tunnel
bounded by the fascial layers over the talus and the inferior extensor
retinaculum, respectively. Several small series of patients undergoing
decompression of the superficial and deep branches have shown the
efficacy of surgical treatment, but large reports guiding decision making in
surgical decompression are lacking.215–219
The common peroneal nerve rests in a particularly superficial position at
the fibular neck and thus is susceptible to external compression as well as
to traction injury. It is also a common site of intraneural ganglia.213
Neuropathy is commonly found in women who habitually sit in a cross-

5122
legged position. Similarly, prolonged squatting or kneeling can cause
compressive symptoms. Repetitive plantarflexion and inversion of the foot
is often the mechanism of traction on the nerve, and a constricting band at
the level of the fibular head is often found at the time of operation.
Symptoms most commonly include foot drop, weakness of ankle,
dorsiflexion and eversion, and pain in the peroneal nerve dermatome along
the lateral leg. The pain symptoms can be easily confused with such
common ailments as shin splints or tibial stress fracture as well as with an
L5 radiculopathy or compartment syndrome. Electrodiagnostic studies are
helpful in isolating the region of entrapment.220
Surgical decompression must not be delayed, although conservative
management is successful in approximately one-third of cases.221 In one
analysis, 87% of patients with motor dysfunction obtained good
improvement, whereas only 54% of patients with purely sensory deficits
experienced long-term relief.222 However, the average time between onset
of symptoms and operation was 14 months in this study. In another series,
surgical intervention was shown to yield a 97% immediate success rate
when performed within 2 months of onset of injury, whereas in cases
lasting 4 to 8 months, only a 38% benefit was found.223

Dorsal Rhizotomy and Ganglionectomy

BASIC CONSIDERATIONS
The Bell-Magendie model describes a dorsal root composed solely of
primary afferent fibers, whereas the ventral root contains only efferent
fibers. Dorsal rhizotomy and ganglionectomy procedures seek to take
advantage of this apparent physiologic segregation to halt the inflow of
nociceptive signals to the spinal cord at particular levels while sparing
motor outputs. Injury to motor fibers in the ventral root is avoided (Fig.
103.3). No neuroma forms at the cut ends of the rootlets, as nerve fibers
that enter the spinal cord are deprived of their cell body and hence
degenerate.224

5123
FIGURE 103.3 Dorsal rhizotomy. A: Location of midline dorsal incision for T4–T7 dorsal
rhizotomy. B: Intradural dorsal rhizotomy with application of metal clip on the rootlets of a root
already transected above and being applied to the rootlets of a root below just prior to sectioning
them. Inset on the right depicts extradural dorsal rhizotomy showing division of the dorsal root
central to the ganglion prior to extirpation of the ganglion by a lesion that will be made just distal to
the ganglion. C: Expected area of sensory loss following right T4–T7 dorsal rhizotomy.

Theoretically an appealing treatment option for pain, rhizotomy in

practice often fails to confer the lasting benefit that one might expect.
Early surgeons performed dorsal rhizotomy for a broad range of conditions
including stump pain, intercostal neuralgia, angina, visceral pain, and
spastic hemiplegia. After comparing operative results for pain with those
for spasticity in 1911, Groves225 remarked, “Strangely enough, the
division of the posterior spinal roots has given the least satisfactory results
in those very cases where we should have expected it to be the most
efficient . . . the relief of pain.”
An important problem with rhizotomy is that the sensory afferents that
arise from a region of the body may provide contributions to multiple
spinal nerves. Conversely, fibers from a single spinal nerve may innervate
multiple segments of the spinal cord. As a result, sensory dermatomes
overlap considerably, so that ablation of a single dorsal root produces little
sensory deficit.226 The earliest studies227,228 of the dermatomes
appreciated this complexity, and early surgeons performed rhizotomy at
two to three levels or more to achieve pain control.225 Extensive
remodeling of sensory dermatomes, attributed to intraspinal sprouting of
dorsal root axons,229 functional reorganization of existing sensory
pathways,230 and other mechanisms, has since been described.
A second potential explanation of surgical failure involves the presence
of unmyelinated sensory fibers in the ventral roots. In 1894, Sherrington

5124
noted degeneration of fibers on the cord side of a transected ventral
root.231,232 He suggested that these fibers, which he presumed would
double back and reenter the cord through the dorsal root, might provide a
physiologic basis for the observation that stimulation of the ventral root
results in pain. Microscopy has demonstrated that some fibers do, in fact,
enter the cord through ventral roots, cross the ventral horn, and synapse
within the dorsal horn or enter the dorsal columns.233 Thus, dorsal
rhizotomy may fail ultimately because of the presence of afferents that
reach the spinal cord via the ventral root. However, the actual frequency of
ventral root sensory nerves is not known.
To obviate this problem, consideration may be given to performance of
a sensory ganglionectomy. The cell body for all primary afferents is
believed to reside in the dorsal root ganglion regardless of whether the
fibers reach the spinal cord via the dorsal or ventral roots. One report cites
a patient with recurrent pain following dorsal rhizotomy that experienced
enduring pain relief following removal of the dorsal root ganglia at the
same level,234 providing further evidence that afferents concerned with
pain may enter the spinal cord through ventral roots. Ganglionectomy has
gained acceptance in the treatment of certain pain disorders.235 However,
including ganglionectomy in a dorsal rhizotomy has not been
demonstrated to yield better long-term results, although late recurrence
with ganglionectomy is also common.

CLINICAL CONSIDERATIONS
Preoperative Evaluation
Dorsal rhizotomy or sensory ganglionectomy may be attempted for
treatment of both nociceptive and neuropathic pain, although in our
experience, pain often recurs within a few years. Prediction of the potential
effect of an operation can be fairly simple, if only a single level is affected.
A number of confounding anatomic situations, such as root-to-root
anastomosis or overlap of root innervation, must be considered.236
Identification of the appropriate spinal level and roots or ganglia for
ablation is accomplished through paravertebral local anesthetic nerve
blocks. Spinal epidural or subarachnoid blocks can be used for screening
purposes when considering sacral rhizotomy. For greater accuracy in

5125
diagnosis, these blocks should be performed at multiple levels, with
placebo controls. There is a tendency for the anesthetic to leak into the
epidural space, and this may lead to a false-positive result.
Although rhizotomies are now done infrequently for pain, some patients
do gain enduring pain relief from rhizotomy or ganglionectomy, with
acceptable morbidity. The challenge is to select the patients most likely to
benefit. Feasibility dictates the appropriate procedures to some extent. If
the clinical problem is limited to one root, ganglionectomy has appeal in
order to avoid the problem of ventral root afferents. Unfortunately,
surgical ganglionectomy involves destruction of a substantial portion of
the facet and therefore may not be practical if two or more roots are
involved. Rhizotomy may be preferable in this instance; however, the
problem of pain recurrence may be higher. No clinical studies directly
compare rhizotomy and ganglionectomy, and differences in outcome
between the two procedures are not well understood.
Dorsal rhizotomy and sensory ganglionectomy spare motor efferents
and do not lead to the formation of neuromas. However, careful attention
must be given to the potential complications of dorsal root surgery.
Ablations of the dorsal roots attenuate not only pain but also vibratory,
temperature, and proprioceptive inputs. Loss of these sensory functions
may be troublesome particularly in the extremities. In addition, with the
ablation of the highly vascularized dorsal roots, blood supply to the spinal
cord can be jeopardized. Ablation of more than six dorsal roots increases
this risk considerably.226 Finally, dorsal rhizotomy and ganglionectomy, if
unsuccessful, preclude the use of dorsal column stimulation as a means of
pain treatment because the primary afferents on which the stimulator acts
undergo wallerian degeneration.
The following case presents evaluation and treatment of a patient with
neuropathic pain, in an ideal setting for performance of a ganglionectomy,
although with eventual pain recurrence.
A 42-year-old woman underwent an anterior cervical discectomy and
fusion with harvesting of a bone graft from the left iliac crest. An anterior
abdominal wall hernia developed at the site of bone harvest. This defect
was repaired with mesh, and the patient developed severe pain at the repair
site. Eventually, the repair site was explored, and injury to the subcostal

5126
nerve (T12) was noted. The neuroma was resected back and relocated to a
healthy muscular bed away from scar. Pain was relieved for several weeks
and then returned. An additional attempt at neuroma relocation surgery
met with the same fate. Opioid treatments as well as other pharmacologic
approaches failed to provide satisfactory relief. Nerve root blocks of T12
but not of T11 or L1 led to complete pain relief. A ganglionectomy was
performed at T12, and the patient had sustained pain relief for 2 years.
In this case, pain was limited to a single, clearly defined spinal level.
The return of pain following neurectomy demonstrated the high likelihood
of reformation of a painful neuroma. A single ganglionectomy both
eliminated the pain and precluded the reformation of a painful neuroma.
However, the pain recurred after 2 years. In our experience, peripheral
nerve stimulation, spinal cord stimulation, and intrathecal pain pumps may
be preferable and nondestructive first-line therapies for radicular pain prior
to performance of sensory rhizotomy or ganglionectomy.

Operative Technique
Dorsal rhizotomy is performed using either an intradural or extradural
approach, whereas ganglionectomy is by extradural approach. For
intradural rhizotomy, a laminectomy is performed at the levels of interest
and the dura is opened, where sensory rootlets are then identified at the
intervertebral foramina, followed proximally, and divided. For extradural
rhizotomy, the lateral facet is removed and the appropriate nerve roots are
exposed laterally. The proximal spinal root is dissected free, and the dorsal
rootlet is identified and divided. For ganglionectomy, the dorsal root
ganglion is also dissected free and removed. In some cases, separation of
the ganglion from the motor root is difficult, and there may be resections
of this structure as well, a factor to be borne in mind when selecting the
ablative approach. Ganglionectomy can also be performed from a
foraminal approach with minor disruption of the facet. Sacral rhizotomy
may be accomplished through sacral laminectomy and division of the
thecal sac between the S1 and S2 roots.237

INDICATIONS AND OUTCOMES

Indications for dorsal rhizotomy or ganglionectomy may be broadly

5127
divided into procedures for cancer and noncancer pain238 and are outlined
by the Joint Section on Pain in its 1994 recommendations. In addition,
dorsal rhizotomy can be a useful therapy in treatment of certain spasticity
disorders, including spastic cerebral palsy. Barrash and Leavens239
reported success in 70% (50 of 71) of patients with cancer, with 10.5-
month average follow-up. By contrast, Onofrio and Campa240 reported an
overall success rate of 41% (46 of 112) in patients with localized
idiopathic pain. Wilkinson and Chan241 reported excellent pain reduction
in 74% of patients with dorsal root ganglionectomy alone, with no adverse
complications, for pain refractory to other treatments. The differences in
success rate between cancer and noncancer pain could potentially result
from earlier mortality among patients with cancer-related pain, given the
significant incidence of late-recurring pain.

Cranial and Cervical Pain

Rhizotomy of C1–C4 in combination with cranial nerves V, IX, and X
may provide effective pain relief from extensive head and neck cancers.242
In considering such a procedure, one would have to consider the morbidity
of such an extensive operation in terms of sensory loss. In some cancer
victims, however, sensory loss is already extensive. Dorsal cervical
rhizotomy may also be combined with trigeminal tractotomy. Cancers of
the lung or breast with brachial plexus involvement, with loss of function
in the upper limb, may also benefit from cervical rhizotomy.

Occipital Neuralgia
The greater occipital nerve, formed by the posterior primary ramus of C2,
and the lesser occipital nerve, formed by the C2 and C3 roots in the
cervical plexus, jointly innervate the occipital region of the scalp. Occipital
neuralgia is headache, characterized by severe paroxysmal lancinating or
continuous pain, localized to this innervated region.243 Occipital neuralgia
may be due to migraine, compression of the C2 root, entrapment of greater
occipital nerve at the superior nuchal line, or nerve injury.244
C2 or C3 ganglionectomy, as well as upper intradural cervical
rhizotomy, have been used successfully in treatment of occipital neuralgia.
Stechison and Mullin245 reported success in 4 of 4 patients with idiopathic

5128
greater occipital neuralgia, with 2-year average follow-up. Lozano et al.246
reported that patients with occipital neuropathic pain due to trauma are
more likely to experience significant pain reduction following C2
ganglionectomy than other patient groups with occipital pain. Onofrio and
Campa240 reported relief from occipital neuralgia in 64% (9 of 14) of
patients immediately and 50% (7 of 14) of patients after months to years
following ablation of 1 to 3 cervical roots. Dubuisson247 reported success
in 71% (10 of 14) of patients, with 33-month average follow-up, following
partial posterior rhizotomy at C1–C3. Cervical nerve block has been
shown to be useful for confirmation of occipital neuralgia and possibly as
a patient selection tool for rhizotomy.248 In a recent study, Acar and
colleagues reported the return of pain within a year in 65% (13 of 20) of
patients undergoing C2 or C3 ganglionectomy.249 Occipital nerve
stimulation may be considered a favorable alternative to C2 or C3
ganglionectomy.250 However, future work must be completed to further
optimize this technology.251
All other recent studies recapitulate what is already been said.

Thoracic Pain
Pain associated with chest wall invasion of pleural-based or chest wall
malignancies, as well as localized thoracic pain secondary to nerve
invasion or compression, can be an indication for dorsal rhizotomy or
ganglionectomy. Arbit et al.252 reported complete pain relief in 64% (9 of
14) and 50% to 100% pain relief in an additional 29% (4 of 14) of patients
with cancer pain, with 22-month median follow-up, following thoracic
dorsal and ventral rhizotomy. Smith253 reported success in 10 of 10
patients with intercostal pain due to thoracotomy (7), herpes zoster (2), and
cancer (1), following thoracic ganglionectomy.

Postsurgical Truncal Pain

Persistent pain following thoracotomy or laparotomy may be responsive to
dorsal rhizotomy. White and Kjellberg226 reported successful treatment of
intercostal neuralgia in 3 of 4 patients, with 8-month median follow-up,
following thoracic rhizotomy. Loeser238 reported success in 33% (1 of 3)
of patients at more than 3 months. By contrast, Onofrio and Campa240

5129
reported on 18 patients with postthoracotomy pain and 5 patients with
postlaparotomy pain, none of whom obtained benefit. White and
Kjellberg226 also reported successful treatment of postherniorrhaphy
neuralgia in 3 of 4 patients, with 2-year median follow-up, following
thoracolumbar rhizotomy. There are no large series of patients on which to
base management decisions.
One case report demonstrated complete resolution of pain symptoms
from postthoracotomy pain syndrome using spinal cord stimulation at 4-
month follow-up. However, the authors cite that this technique must be
further researched and refined.254

Sacral Pain
Cancers of the colon, rectum, urinary tract, cervix, and prostate may result
in pain attributable to sacral roots. Unfortunately, ablation of the second
and third sacral roots may affect bladder, sphincter, and sexual function.
Thus, sacral root division is indicated in cases of pelvic cancer pain, where
patients have already lost bladder and bowel function. It is a simple
procedure that may confer striking benefit. Saris et al.255 reported success
in 47% (7 of 15) of patients with colorectal cancer presenting with perianal
pain, with 1-year median follow-up, following bilateral S3–S5 rhizotomy.
Felsoory and Crue237 reported satisfactory results in 69% (20 of 28) of
patients with colorectal (17), cervical (5), anal (3), and other (3) cancers,
with unstated follow-up duration, following transection of the cauda
equina at L5/S1. The surgical anatomy is depicted in Figure 103.4.

5130
FIGURE 103.4 Technique of extradural sacral rhizotomy. An S1 laminectomy is performed, and
thecal sac is dissected out circumferentially between S2 and S3, doubly ligated, and divided.
(Reprinted by permission from Springer: Burchiel KJ. Neurosurgical procedures of the peripheral
nerves. In: North RB, Levy RM, eds. Neurosurgical Management of Pain. 1st ed. New York:
Springer-Verlag; 1997:133–161. Copyright © 1997 Springer Science+Business Media New York.)

A 14-year single-center study showed an 87.5%, 84.8%, and 73%

improvement in patients with idiopathic urinary retention, urgency urinary
incontinence, and painful bladder syndrome with sacral
neuromodulation.256 This technology has, however, been studied and used
more in the treatment of fecal incontinence.

5131
Extremity Pain
Rhizotomy or ganglionectomy is indicated for denervation of a
functionally useless limb. There are few other indications in the treatment
of extremity pain. That multiple roots may be involved, the morbidity of
sensory loss, and the problem of frequent pain recurrence, lead to
infrequent use of these procedures for extremity pain. Ganglionectomy for
monoradicular extremity pain has been proposed but remains unproven.257
North et al.258 reported greater than 50% relief from failed back surgery
syndrome in none of the 13 patients they studied, with 5.5-year average
follow-up.258 By contrast, Taub et al.259 reported success in 59% (36 of
61) of patients with intractable monoradicular sciatica following dorsal
root ganglionectomy, with 5- to 9-year median follow-up. This unusually
high rate of success likely reflects very careful patient selection.
The choice of rhizotomy or ganglionectomy for treatment of extremity
pain requires a balance between compromise of function due to
elimination of sensation and the elimination of pain. For the upper
extremity, White and Kjellberg226 reported successful treatment of diffuse
upper extremity pain in 50% (7 of 14) of patients, with 3-year median
follow-up, following rhizotomy at various levels. Following the procedure,
none of the patients complained of unpleasant numbness or clumsiness of
the hand, perhaps reflecting the seriousness of the preoperative condition.
In the lower extremity, they reported successful treatment of lateral
femoral cutaneous neuralgia in 67% (4 of 6) of patients, with 3-year
median follow-up, following L2–L3 rhizotomy. Spinal cord stimulation
may offer a nondestructive alternative to rhizotomy or ganglionectomy for
the treatment of extremity pain. In addition, recent work has shown that
stimulation of the dorsal root ganglion at certain spinal levels provides
longer lasting relief than does traditional spinal cord stimulation. Yang and
Hunter260 reported successful treatment of traditional spinal cord
stimulator failed CRPS in two patients with the use of dorsal root ganglion
stimulation. Huygen and colleagues261 reported 50% improvement in
patients with failed back surgery syndrome who had undergone L2–L3
dorsal root ganglion stimulation. Although this technology is continuing to
be refined and studied, these nonablative and modifiable methods of
improving pain outcomes may indeed show promising outcomes over

5132
more traditional ablative procedures.

Visceral Pain
Although rarely used today due to the advent of other techniques, dorsal
rhizotomy has been reported to be highly effective in controlling visceral
pain. White and Kjellberg226 reported successful treatment of medically
intractable angina in 75% (3 of 4) of patients, with 14-month median
follow-up, following T1–T4 rhizotomy. Success was 50% (3 of 6) for
treatment of other forms of visceral pain.226
Peripheral subcutaneous nerve stimulation has been recently introduced
as a new technology to improve the symptoms of abdominal pain from a
variety of sources including hernia repair and painful surgical scars.
However, no long-term trails have been completed to prove its
effectiveness.

Axial Spine Pain

Lumbar median branch rhizotomy via percutaneous radiofrequency
ablation is indicated for treatment of facet arthropathy pain and is
discussed in detail in Chapter 102. Local and radicular pain due to lumbar
spine disease is largely unresponsive, in the longer term, to dorsal
rhizotomy. Loeser238 reported success in 75% (12 of 16) at up to 3 months
but only 14% (2 of 14) at more than 3 months for patients with disk
disease. Onofrio and Campa240 reported improvement in 17% (11 of 64) of
patients with lumbosacral pain following rhizotomy, with unstated follow-
up. Wetzel et al.262 reported success in 55% (28 of 51) at up to 6 months
and 19% (7 of 37) at 2 years for patients with lumbar radiculopathy after
lumbar surgery.
Taub and colleagues259 reported similar findings in that patients with
intractable radicular pain who underwent ganglionectomy, 59% achieved
reduced or eliminated pain symptoms. However, dysesthesias developed in
a significant number (60%) of these patients. Therefore, there may be a
role for ganglionectomy in the treatment of axial spine pain, but it must be
weighed against the development of other painful symptoms (dorsal root
ganglion for intractable monoradicular sciatica).

5133
Postherpetic Neuralgia
Dermatomal pain following herpetic infection responds poorly to dorsal
rhizotomy. Loeser238 reported failure in 2 of 2 patients. Onofrio and
Campa240 reported success in only 20% (1 of 5) of patients, with 5-year
follow-up, following unilateral rhizotomy. The treatment of postherpetic
neuralgia is discussed in Chapter 27. A 2002 study showed 82% of
patients with postherpetic neuralgia treated with spinal cord stimulation
showed long-term pain relief and significant improvement in pain-limiting
activities of daily living. In fact, 8 patients in the study had their
stimulators removed between 3 and 66 months postimplantation because
of complete pain relief, possibly suggesting that the stimulation induces
some form of plasticity within the central nervous system to achieve
complete resolution of pain symptoms.263

Sympathectomy
BASIC CONSIDERATIONS
Sympathetic Efferents
Sympathetic efferents reach their target structures in two steps.
Preganglionic sympathetic efferents arise in the intermediolateral cell
column of the spinal cord at T1–L3. Thinly myelinated fibers emerge in
the ventral roots and transit briefly through the spinal nerve before exiting
to form the white rami communicantes, leading to the paravertebral
sympathetic ganglia. Some preganglionic fibers form synapses in the
sympathetic chain with postganglionic neurons, from which unmyelinated
fibers return to the spinal nerves, forming the gray rami communicantes.
These postganglionic efferents provide sympathetic innervation to blood
vessels, sweat glands, and other structures. Other preganglionic fibers pass
through the paravertebral sympathetic chain without forming synapses and
continue to the prevertebral ganglia. In the prevertebral ganglia, these
efferents synapse with postganglionic effector neurons. From the
prevertebral ganglia, unmyelinated fibers innervate the abdominal and
pelvic viscera. Sympathectomy has been used in the treatment of pain from
the limbs, the heart, and abdominal viscera. Presacral neurectomy and
thoracic sympathectomy for cardiac pain are discussed earlier in this

5134
chapter and are not further addressed here.

Sympathetically Maintained Pain

In some patients with chronic pain syndromes, the pain depends on the
activity of sympathetic efferents in the painful area. This pain, termed
sympathetically maintained pain (SMP), is defined as that aspect of pain
that is relieved by blockade of sympathetic efferents.264 Pain that is
unaffected by the activity of sympathetic efferents is termed
sympathetically independent pain. The diagnosis of SMP is empiric; that
is, it is made based on response to treatment. In any pain syndrome, a
portion may be sympathetically maintained, although another part is
sympathetically independent. Notably, CRPS and other neuropathic
conditions may or may not be associated with SMP.
Traditionally, three distinct mechanisms have been considered as ways
through which ablation of sympathetic nerves or ganglia may lead to pain
relief:
1. The sympathetic efferents in T1–L3 that pass through paravertebral
sympathetic ganglia to abdominal and pelvic viscera do not travel
alone. They are accompanied by afferents, with cell bodies in the
dorsal root ganglia of T1–L3, which convey sensory information
about distension and inflammation of visceral organs to the central
nervous system. As a result of this colocalization, ablation of
prevertebral ganglia (or the nerves originating from them) interrupts
the flow of nociceptive signals from visceral structures to brain,
thereby producing pain relief. Hence, as a treatment for visceral pain,
sympathectomy is a form of sensory neurectomy.
2. Sympathectomy may improve pain associated with ischemia.
Sympathetic efferents maintain arterial tone. In vasospastic and
vasoocclusive conditions, the vasodilation consequent to
sympathectomy may ameliorate ischemia, thereby decreasing
pain.265
3. Finally, sympathectomy may eliminate norepinephrine-mediated
activation of nociceptors and thereby relieve SMP. In this section, we
concentrate on this latter mechanism and extremity pain related to
CRPS in which a component of pain has been demonstrated to be

5135
 sympathetically maintained.
Understanding of the pathophysiologic mechanisms underlying SMP
continues to increase. The involvement of both A and polymodal C
nociceptors is evident although incompletely elucidated.266,267
Immunologically mediated mechanisms involving prostaglandin,
bradykinin, substance P, neuropeptide Y, and calcitonin gene-related
peptide have also been proposed in treatment-resistant patients.268,269
Increased expression of class I and II human leukocyte antigen in patients
diagnosed with reflex sympathetic dystrophy suggests a genetic
predisposition to poor treatment response,270 although a relationship to
SMP has not been defined.
By definition, SMP is eliminated by blockade of sympathetic efferent
innervation of the painful area. Thus, anesthetic blockade of the relevant
sympathetic ganglia relieves pain in patients with SMP. Stimulation of the
sympathetic chain evokes pain in patients with SMP but not in those
without SMP.25 Moreover, Walker and Nulson271 noted that stimulation of
the severed distal end of the sympathetic chain evokes pain in those
diagnosed with SMP but not in other patients. Thus, the central
connections of sympathetic efferent fibers are not required for stimulation
of the sympathetic system to evoke pain. These observations establish that
efferent sympathetic fibers, rather than afferent sensory fibers that may
travel with sympathetic fibers, account for SMP in nonvisceral pain
syndromes.
Several independent lines of pharmacologic evidence support the claim
that norepinephrine released from sympathetic fibers is critical in SMP.
First, regional infusion of guanethidine, which acts to deplete
norepinephrine from sympathetic terminals, relieves pain in patients with
SMP.272 Second, in patients whose pain had been relieved by either
sympathetic block or sympathectomy, a cutaneous injection of
norepinephrine into the previously painful area rekindles the pain and
hyperalgesia. However, norepinephrine injected intracutaneously into
normal subjects induces less pain and less hyperalgesia.273,274 Finally,
administration of sympathetic β-adrenergic antagonists, such as prazosin,
phenoxybenzamine, or phentolamine, relieves SMP.273,275–277
Following nerve injury, neuromas that form may acquire sensitivity to

5136
norepinephrine. Injection of pH-balanced norepinephrine solution into
normal subcutaneous tissues causes little pain. However, injection of
norepinephrine onto painful neuromas does induce pain.278 Thus, nerve
injury may be associated with the induction of SMP.
These observations suggest that an abnormal increase in the amount of
norepinephrine released from sympathetic terminals is not likely to be the
mechanism of SMP. Rather, it is the response to norepinephrine that
appears to be critical. Studies continue to support this theory,
demonstrating the benefit of perioperative pharmacologic sympathetic
block in reducing recurrence.279,280 Whether this change is due to an
upregulation of β-adrenergic receptors or increased receptor sensitivity is
unknown.

CLINICAL CONSIDERATIONS
Preoperative Evaluation
SMP cannot be diagnosed purely from history and physical examination of
the patient.281 However, it must be differentiated from similar-appearing
chronic pain syndromes, particularly peripheral nerve injury. A number of
clinical features are helpful: (1) In general, SMP does not occur in places
other than the extremities or face. As a rule, the likelihood of developing
SMP parallels the density of sympathetic innervation of the skin. Hence,
truncal pain is far less likely to be due to SMP than is extremity pain. (2)
Signs that may be inferred to represent increased sympathetic activity in
the painful area do not necessarily denote the presence of SMP.282 For
example, limbs associated with SMP may be warmer, cooler, or the same
temperature as unaffected limbs. Similarly, differences in sweating, nail
growth, and muscle tone do not reliably contribute to the diagnosis of
SMP. Nonetheless, sweating abnormalities in particular, as well as
temperature alterations in general, may have some diagnostic utility.283
We have found that among patients with traumatic nerve or soft tissue
injury with touch-evoked pain, all patients with SMP and 50% of patients
with sympathetically independent pain have striking sensitivity to mild
cooling stimuli.7,284
Due to adverse effects and lack of definitive supporting evidence,
surgical sympathectomy is typically reserved for medically refractory

5137
SMP. Careful patient selection is critical to success. Thus, preoperative
evaluation is of great importance. Mechanical allodynia with temperature
change and cooling hyperalgesia together form an indication for
sympathetic blockade.282 The effect of sympathetic blockade via regional
blockade or systemic infusion, in turn, plays an important role in
identifying patients who might benefit from sympathectomy. High rates of
recurrence, either due to sympathetic chain regeneration or new-onset
CRPS, as well as significant adverse effects of the operation, serve to
further highlight the need for discriminating patient selection. Finally,
early intervention is important to optimize patient outcomes.
Quantitative sensory testing: Essentially all patients with SMP have
cooling hyperalgesia.281,284 In fact, patients with SMP often spontaneously
volunteer that the one stimulus that they most dread is cooling of the
painful area. Cooling hyperalgesia occurs less frequently in patients with
sympathetically independent pain. This suggests that cooling hyperalgesia
is a highly sensitive although not specific, indicator of SMP.
Local anesthetic sympathetic ganglion blocks: The traditional
procedure to diagnose SMP is percutaneous injection of local anesthetic
onto the sympathetic ganglia serving the painful region. In local anesthetic
sympathetic ganglion blocks (LASB), ganglia are localized through
anatomic landmarks, ideally under fluoroscopic guidance, and local
anesthetic is injected into the region. The presence of local anesthetic at
the ganglia prevents norepinephrine from being released into peripheral
tissues. Although frequently used to diagnose SMP, LASB results must be
interpreted with care: (1) Incomplete block of individual ganglia may
falsely underestimate the contribution of SMP to a painful condition. The
extent of sympathetic block must be evaluated by assaying for effects of
sympathetic block, such as changes in skin temperature. (2) Spread of
local anesthetic onto somatic afferents in the nerve roots, or blockade of
sensory afferents that accompany sympathetic efferents, may induce pain
relief by way of somatic block rather than sympathetic block. Careful
sensory examination must be performed to ensure that somatic afferents
are not affected by injection of local anesthetic. (3) LASB may evoke a
placebo response, causing overestimation of pain relief. In addition to
these interpretive issues, LASB has some risk. Complications reported

5138
with LASB include pneumothorax, phrenic and laryngeal nerve block,
cardiac arrhythmia, kidney injury, hemorrhage, and inadvertent
intravascular or epidural injections (see Chapter 98 for a detailed
discussion of the role of local anesthetic blocks in the diagnosis of SMP).
Systemic phentolamine infusion: An alternative strategy to assess the
potential efficacy of sympathectomy involves intravenous infusion of
phentolamine, a short-acting antagonist of α-adrenergic receptors.273,276
There is good correlation between pain relief with LASB and that with
systemic phentolamine infusion (SPI).281,285 As a systemic infusion,
phentolamine does not provide any information about anatomic
localization, as is available with LASB. However, SPI has a number of
advantages over LASB: (1) The test is painless in that the phentolamine is
delivered systemically and does not require fluoroscopy or needles to be
placed in the paravertebral space; (2) with SPI, a significant observation
period can be used prior to the administration of the drug, and the patient
can be blinded to the time of drug administration, allowing a placebo-
control period in every trial; and (3) SPI appears to be safer than LASB,
with only nasal stuffiness and peripheral vasodilation reported as side
effects.286 Furthermore, because the activity of nearby sensory afferents is
preserved, SPI appears to be a more specific diagnostic test for SMP.281,285
Intravenous regional block: A third method to detect SMP involves
regional intravenous infusion of an agent that impedes peripheral release
of norepinephrine,272 known as a Bier block. Sympatholytic agents studied
include bretylium, reserpine, and guanethidine.284 To avoid systemic
circulation of the sympatholytic agent, a tourniquet is applied to the limb
during the test. The central advantage of intravenous regional block (IRB)
is localization of sympathetic block to the limb of interest. However, there
are shortcomings: (1) Some patients poorly tolerate the required tourniquet
application; (2) the dramatic release of sympathetic neurotransmitter
accompanying infusion of guanethidine in SMP patients may be severely
painful; (3) the blocking agent may leak beyond the tourniquet, in some
instances with significant hemodynamic effects; (4) the need for a
tourniquet makes IRB difficult to perform either in the trunk or in the
lower extremity; and (5) it is difficult to evaluate placebo responses with
IRB. Although frequently mentioned as a means to diagnose and to treat

5139
SMP, we believe that IRB has few advantages. The same degree of β-
receptor blockade can be achieved with systemic phentolamine.
Medical treatment of sympathetically maintained pain: Once the
diagnosis of SMP is made, the mainstay of treatment is medical
sympatholysis, with surgical intervention reserved for refractory cases. A
remarkable feature of SMP is that extended sympathetic blockade may
lead to long-term or permanent relief from the disorder. When the goal of
blockade is diagnosis, the diagnostic technique should be specific to the
sympathetic nervous system. By contrast, when the goal is treatment, there
need not be specificity. There are several medical and interventional
means by which to achieve sympatholysis. The choice of technique should
be based on considerations of safety, comfort, and efficacy.
Multiple sympathetic ganglion blocks with local anesthetics have, in the
past, served as the criterion standard for treatment. However, local
anesthetic treatment of peripheral nerves may work as well by inducing
similar blockade of the distal sympathetic fibers. For example, SMP in the
upper extremity could be treated either by LASB of thoracic sympathetic
ganglia or by local anesthetic application to the appropriate nerves.
Alternatively, although epidural administration of anesthetic may lack
specificity as a means to diagnose SMP, it may provide an effective
treatment regimen. Epidural clonidine, although limited by hemodynamic
effects, provides extensive analgesia.287 SPI has been used successfully to
treat SMP in a patient with pain in all extremities due to Sjögren’s
associated polyneuropathy.288
When episodic treatments fail to provide adequate relief, chronic
treatment with oral sympatholytics may reduce SMP. Both
phenoxybenzamine and prazosin have been used in this manner.275,277
However, the systemic hypotension that frequently accompanies the use of
these agents may preclude adequate sympathetic blockade. Finally, topical
clonidine, which is likely to inhibit local norepinephrine release, may be a
low-morbidity treatment of SMP in some patients, albeit locally.273,289 If
well tolerated, this and other medical techniques could substantially reduce
the need for surgical sympathectomy; indeed the role for surgical
sympathectomy remains in question.

5140
Operative Techniques
To achieve sympathectomy of the upper extremity, it is necessary to resect
the T2, T3, and T4 sympathetic ganglia. Removal of less than all three
ganglia risks inadequate sympathectomy for pain. One of our patients
required extension of the sympathectomy to T5. This is best achieved
through a thoracoendoscopic technique, although the data on this operation
have been acquired through open supraclavicular transaxillary or posterior
costotransversectomy approaches. By contrast, the lumbar sympathetic
chain, most commonly involving L2 and L3 ganglia, is generally accessed
through an anterolateral retroperitoneal surgical approach. Percutaneous
approaches have been suggested, but these procedures often do not achieve
enduring results. In addition, the scarring produced by these approaches
makes later surgical treatment more difficult.
Many clinicians have reported limited success in the treatment of pain
by surgical sympathectomy.290,291 Failure of sympathectomy may reflect
inadequacies either of the preoperative evaluation, as discussed earlier, or
of the extent of the sympathectomy. For example, sympathetic outflow to
the arm derives predominantly from the T2 and T3 ganglia and not from
the stellate ganglion. Failure to remove the T2 ganglion, at a minimum,
will result in continued sympathetic innervation of the hand. An important
feature in the lower extremity is that sympathetic innervation is often
bilateral. Bilateral lumbar sympathectomy of L2–L4 is typically necessary
(Fig. 103.5). A typical patient history is one of impressive relief of pain
lasting several weeks following an ipsilateral lumbar sympathectomy. The
pain then returns, and at that time, the pain may be relieved by a
contralateral block of the lumbar sympathetic ganglia. Patients will
typically have enduring relief of pain following contralateral lumbar
sympathectomy.292,293 As in the upper extremity, complete
sympathectomy is required for pain relief; the partial denervation that is
successful for vascular diseases is not adequate as a treatment for pain.

5141
FIGURE 103.5 Open lumbar sympathectomy is done through retroperitoneal exposure of the
sympathetic chain. (Reprinted by permission from Springer: Wilkinson HA. Neurosurgical
procedures of the sympathetic nervous system. In: North RB, Levy RM, eds. Neurosurgical
Management of Pain. 1st ed. New York: Springer-Verlag; 1997:162–175. Copyright © 1997
Springer Science+Business Media New York.)

INDICATIONS AND OUTCOMES

Ulmer and Mayfield294 reported successful treatment of 96% (67 of 70) of
soldiers with burning pain due to nerve injury by surgical sympathectomy
of appropriate ganglia. In studies of a civilian population, Manart et al.295
reported a “good” response to thoracic sympathectomy in 59% (13 of 22)
of patients with burning posttraumatic pain, even when diagnostic
blockades were not typically performed. For patients selected for
preoperative diagnostic sympathetic block, Mockus et al.296 reported
improvement in 94% (29 of 31) of patients, with 3.4 years average follow-
up. AbuRahma et al.297 reported 1-year satisfactory improvement of pain
in 20 of 21 patients. Overall success rates of 90% or greater with surgical
sympathectomy have been reported by several groups.298 Thompson299
reported successful surgical treatment in 46% (55 of 120) of patients with
SMP following minor trauma, who were unresponsive to medical therapy.
Overall, long-term successful outcomes in 70% to 85% of cases of
thoracic, and slightly less in lumbar sympathectomy, can be expected.
As noted, results of sympathectomy largely depend on careful patient
selection.277 Our experience has been that patients do extremely well if the

5142
pain responds dramatically to sympathetic ganglion block and systemic
infusion of phentolamine, and there is provocation of pain with injection of
norepinephrine when the patient is under the influence of LASB. Although
our conclusions are preliminary, it appears that if one or more of these
elements are missing, the patient does not fare as well. The modest
response rates to sympathectomy in earlier series may reflect improper
patient selection and inadequate sympathectomy (e.g., bilateral
sympathectomy required for lower extremity pain) or more extensive
unilateral ganglionectomy for total denervation of an extremity.

POSTOPERATIVE COMPLICATIONS
Surgical sympathectomy may be associated with idiosyncratic
complications. One frequent complication, affecting up to 20% to 50% of
patients, is postsympathectomy pain.296,300,301 This condition is
characterized by the sudden onset, a few weeks after the procedure, of
superficial burning pain, deep aching pain, and cutaneous hyperalgesia.302
The pain arises in the proximal regions of limbs and the trunk despite
surgical ablation of sympathetic innervation to the distal limbs. Fortunately
for the majority of patients, postsympathectomy pain resolves
spontaneously in several weeks to a few months, and no further surgical
intervention is warranted.300
Ablation of sympathetic input to a region of skin results in sudomotor
paralysis. In the upper extremity, the resultant dryness can be
uncomfortable. In the lower extremity, dryness is better tolerated. Postural
hypotension also can be a transient problem. However, even in patients
with sympathectomy of all four extremities, this problem is usually not
enduring. Compensatory hyperhidrosis, as well as pathologic gustatory
sweating, may be found in patients following sympathectomy.303 Two
additional complications of sympathectomy include paradoxical
vasoconstriction and ileus. Sympathetic fibers arising from the celiac and
mesenteric ganglia modulate gastrointestinal motility. Both complications
are generally transient.
CRPS is defined as a chronic pain disorder that has a propensity to
affect only one limb (arm, leg, etc.) and is disproportionate in terms of
how long the pain lasts or how intense the pain is compared to any known

5143
trauma or other lesion. It is also a progressive disease that is not confined
to a certain nerve territory or dermatome and has a predilection for
producing distal sensory and motor symptoms including burning
sensations, allodynia, and hyperalgesia.304
SCS has been shown to be beneficial in the treatment of CRPS.
Although traditional SCS is the primary type of SCS that is used clinically,
one study showed that dorsal root ganglion SCS is superior to traditional
SCS for the treatment of CRPS.305 However, traditional SCS has been
shown to be superior to other treatments for CRPS. Kemler and Furnee306
studied a population of patients who were initially unable to work due to
severe pain and disability and were refractory to physical therapy (PT) and
other medical treatments. These patients were then either randomized to a
control group that received only PT or the experimental group that
received SCS and PT. The study showed that the patients who were
randomized to the SCS-with-PT group had a greater than 50% decrease in
their pain at 6 months compared to the PT-only group. Additionally, the
study showed that at 1 year, patients in the SCS-with-PT group had a
marked improvement in their quality of life compared to the PT-only
group. They did not, however, observe any difference in functional status
or psychological depression between the two studied groups.306,307
Another study showed that pain caused by CRPS decreased on average by
45% after treatment with SCS.308 These studies and others demonstrate
that using SCS for medically refractory CRPS is beneficial.

Conclusion
The peripheral nervous system offers a number of attractive strategies for
treatment of pain. Peripheral nerves may be transected or released from
regions of entrapment. Where regional pain control is required, sensory
roots or ganglia may be the targets of therapy. In cases where pain has a
significant sympathetically maintained component, sympathectomy may
offer significant and long-lasting pain relief.
As for all surgical procedures, careful patient selection and clear
establishment of the etiology of the painful condition is critical to ensure
successful analgesia. Enthusiasm for these surgical procedures must be

5144
tempered by a keen appreciation of potential complications.
Nerve transection may either produce or eliminate pain. This leaves the
clinician with the sometimes daunting task of deciding if, when, and how
to perform neurectomy. Each patient must be carefully evaluated. In the
case of minor nerves previously transected, the clinician should not labor
over the decision to relocate the neuroma to a protected, unscarred site. In
this instance, there is little to lose.
Pain due to mechanical compression may be relieved through release of
nerve root entrapments. Carpal tunnel release and release of UNEE are
among the most commonly performed peripheral nerve procedures.
However, many less common forms of nerve root entrapment may be
overlooked or misdiagnosed. A systematic understanding of peripheral
neuroanatomy on the part of the pain clinician is essential to accurate
diagnosis and treatment of these pain syndromes.
Dorsal rhizotomy is seldom used in modern practice, but a survey of the
existing literature reveals that patients certainly exist in whom rhizotomy
conferred long-term benefit. Today’s pain clinician does well to keep this
option in mind in properly selected cases. Ganglionectomy has certain
theoretical advantages over rhizotomy and neurectomy and is still another
technique that should be considered in certain cases. However, recurrence
of pain several years after surgery may be quite common.
Sympathectomy is helpful in patients with persistent SMP who are
refractory to medical management. Recognition of the clinical symptoms
of SMP, such as cold allodynia, and appropriate selection of sympathetic
blockade modalities are required to make the diagnosis and to provide a
successful treatment strategy. Hence, the key to success with this
procedure, as with most surgery, is meticulous patient selection and proper
execution of the operation.
Peripheral electrical neuromodulation, a nonablative surgical
intervention for the treatment of pain, is emerging as a promising
therapeutic approach for well-selected patients. This technology is still
evolving, and further research will need to be conducted to objectively
show improvements in the quality of pain improvement as well as the
exact mechanism by which this technique works on a cellular and network
basis.

5145
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CHAPTER 104
The Surgical Management of
Trigeminal Neuralgia
MATTHEW K. MIAN, SARAH K. BICK, PRATIK A. TALATI,
and EMAD N. ESKANDAR

Trigeminal neuralgia (TN), formerly known as tic douloureux, is a chronic

pain disorder affecting the trigeminal nerve. Clinically, TN is
characterized by bouts of severe, lancinating pain in a trigeminal
distribution, often triggered by light touch or facial movement. A variety
of effective medical and surgical therapies exist for TN. Carbamazepine
(Tegretol) is considered the first-line treatment; second-line medications
include oxcarbazepine and lamotrigine, among others.1 Opiates are not
particularly effective.2 Surgical therapies include microvascular
decompression (MVD), percutaneous rhizotomy, and radiosurgery. In this
chapter, we review the surgical management of TN.

Patient Presentation
TN is rare, with an incidence of 2 to 5 per 100,000 per year3 and a
prevalence of 0.03% to 0.3%.4 Patients typically present in their 60s,5
although some develop symptoms as early as their late 30s. There is a
female preponderance (3:2), and some studies suggest an association with
arterial hypertension.3 Case reports have identified familial forms of TN;
these appear to be rare, are sometimes bilateral, and may follow an
autosomal dominant inheritance pattern.6,7
Patients typically present with one of two clinical syndromes.8 Type 1
TN (“typical TN”) is characterized by a predominance of brief,
lancinating, or electrical unilateral pain. Type 1 TN most frequently occurs
in the V2 or V3 division, and it does not cross the midline. Triggers may
include tactile stimuli or facial movements such as talking or chewing, and

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there is usually a refractory period during which pain cannot be elicited.
The duration of pain is often brief, lasting seconds, but there may be up to
several minutes of paroxysms before the pain-free refractory period.8 The
International Headache Society diagnostic criteria for TN are outlined in
Table 104.1.9

TABLE 104.1 Diagnostic Criteria for Trigeminal Neuralgia from

the International Headache Society
A. At least three attacks of unilateral facial pain fulfilling criteria B and C
B. Occurring in one or more divisions of the trigeminal nerve, with no radiation beyond the
trigeminal distribution
C. Pain has at least three of the following four characteristics:
Recurring in paroxysmal attacks lasting from a fraction of a second to 2 minutes
Severe intensity
Electric shock-like, shooting, stabbing, or sharp in quality
Precipitated by innocuous stimuli to the affected side of the face
D. No clinically evident neurologic deficit
E. Not better accounted for by another ICHD-3 diagnosis
ICHD-3, International Classification of Headache Disorders, 3rd edition.

Type 2 TN (“atypical TN”) is characterized by a predominance of

constant pain, often burning or aching.10 This pain usually exists in
addition to the brief, lancinating pain that occurs in type 1 TN. Although
not firmly established, some believe that type 2 TN may emerge from
long-standing type 1 TN.11

Anatomy
The trigeminal nerve contains motor and sensory fibers that exit the lateral
brainstem at the level of the mid-pons. Just distal to the brainstem root
entry zone (REZ), the nerve transitions its myelinating cells from central
oligodendrocytes to peripheral Schwann cells. This transition zone, which
occurs several millimeters from the REZ at about one-third to one-fourth
of the distance to Meckel’s cave, is believed to be particularly sensitive to
mechanical irritation.
The cisternal segment of the nerve traverses the subarachnoid space,
traveling anterolaterally to pierce the dura near the petrous apex to enter
Meckel’s cave, a CSF-filled space between two layers of dura over the

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petrous portion of the temporal bone.12 The nerve then splits into three
divisions: (1) ophthalmic (V1; sensory only), which travels through the
superior orbital fissure to enter the orbit; (2) maxillary (V2; sensory only),
which enters the pterygopalatine fossa via the foramen rotundum; and (3)
mandibular (V3; motor and sensory), which exits the skull through the
foramen ovale (FO).

Pathophysiology
Type 1 TN is classically believed to stem from mechanical irritation of the
trigeminal nerve by a blood vessel.13–15 Under this model, pulsatile
vascular compression causes focal irritation and eventually demyelination.
The superior cerebellar artery (SCA) is most commonly implicated (75%),
with other offenders being the anterior inferior cerebellar artery (10%),
posterior fossa veins (12%), vertebral artery (2%), posterior inferior
cerebellar artery (1%), and the basilar artery (1%).16
Injured trigeminal axons become hyperexcitable, spilling excitatory
neurotransmitters that depolarize neighboring cells via ephaptic
conduction (the “ignition hypothesis”) and incite synchronized
afterdischarges.10,17 Periodic waves of depolarization are experienced as
paroxysms of pain in the trigeminal distribution, often corrupting the
perception of normal tactile stimuli.
Type 2 TN is posited to result from deafferentation of higher order
somatosensory neurons, similar to other types of chronic neuropathic
pain.10 Some have proposed that type 1 and 2 TN sit at opposing ends of a
single spectrum.11 Chronic nerve injury in the setting of type 1 TN may
extend proximally to and beyond the REZ, precipitating type 2 TN
symptoms.18
First-line medical therapy consists of carbamazepine. The mechanism of
carbamazepine’s efficacy is unknown, although it is speculated that
blockade of voltage-sensitive sodium channels may stabilize
hyperexcitable cell membranes, reducing aberrant action potential
propagation.19
MVD, described in the following text, yields immediate cessation of
pain in many patients suffering from TN. The mechanism remains a

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subject of debate, but several hypotheses have been put forward. First,
mechanical compression generates ectopic action potentials that may be
alleviated by decompression.20,21 Second, ephaptic conduction may be less
effective when a compressive force is removed because there is more
relative distance between demyelinated axons. Finally, there may be a
pressure-dependent mechanical conduction block on subpopulations of
fibers that is dissolved upon decompression.2

Evaluation for Surgery

Surgery should be considered for patients with persistent, severe
symptoms despite adequate drug therapy or those with intolerable
medication side effects. Medication trials at a minimum should include
carbamazepine or oxcarbazepine.
An evaluation for surgery should prompt scrutiny of the patient’s
diagnosis. There exists a cornucopia of facial pain disorders. TN is a
clinical diagnosis, and certain red flags should give the clinician pause:
pain that does not respect the midline, age <40 years, absence of any initial
response to carbamazepine, and facial numbness, among others.
Surgical options for TN can be divided into two categories: palliative
ablative procedures (e.g., percutaneous rhizotomy, stereotactic
radiosurgery) and nondestructive MVD. Neuromodulatory techniques are
growing in popularity for a select set of facial pain disorders, but there is
insufficient evidence or experience to support their use as a first-line
surgical option for type 1 or 2 TN.
Regarding procedure selection, Slavin and colleagues22 developed a
facial pain surgical algorithm that is concordant with our own experience
(Fig. 104.1). MVD is best reserved for those patients with type 1 TN,
although some data suggest it may alleviate episodic pain in type 2 TN
patients as well.23 Radiofrequency rhizotomy and other percutaneous
variants (glycerol, balloon compression) may be used for both type 2 TN
patients and those type 1 TN patients in whom medical comorbidities or
personal preferences preclude a retrosigmoid craniotomy or those who
have already failed an MVD. Radiosurgery is an option for those patients
seeking to avoid an invasive procedure.

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FIGURE 104.1 Surgical treatment algorithm for trigeminal neuralgia (TN) types 1 and 2.
(Adapted from Slavin KV, Nersesyan H, Colpan ME, et al. Current algorithm for the surgical
treatment of facial pain. Head Face Med 2007;3:30).

Imaging is mandatory in the presurgical evaluation, primarily to rule out

pathologies that would be symptomatic of TN yet mandate different
treatment, namely, posterior fossa tumors or vascular malformations,
multiple sclerosis (MS), and brainstem or thalamic infarctions. The
preferred imaging study is a magnetic resonance scan with a thin-cut axial
T2-weighted 3D sequence (e.g., constructive interference in steady state
[CISS], fast imaging employing steady-state acquisition [FIESTA], or
similar) through the brainstem. Such sequences delineate the trigeminal
nerve in high resolution. Of particular interest is contact or compression of
the cisternal component of the trigeminal nerve by a blood vessel (Fig.
104.2).

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FIGURE 104.2 Axial (left) and sagittal (right) fast imaging employing steady-state acquisition
magnetic resonance imaging sequences demonstrating neurovascular compression of the superior
aspect of the left trigeminal nerve (yellow asterisks) by a loop of the superior cerebellar artery
(SCA; red arrowheads). Note the displacement and atrophy of the proximal nerve segment on the
axial image. On the sagittal image, only a narrow cross-section of the nerve is captured, but the
looping course of the SCA is apparent.

Importantly, the presence of a vessel compressing the trigeminal nerve

is not an obligate criterion for MVD candidacy, as some TN patients
without radiographic neurovascular compression (NVC) are indeed found
to have NVC at surgery, and asymptomatic NVC is frequently observed
both in healthy controls and on the contralateral (unaffected) side in
patients with TN.24,25 It does appear, however, that imaging features such
as nerve displacement and atrophy may be more specific, although less
sensitive, for predicting whether radiographic NVC is symptomatic.26,27

Microvascular Decompression
MVD remains the preferred surgical treatment for medically suitable
patients with type 1 TN. MVD offers a high success rate, the longest
duration of pain relief, and is nondestructive, thus avoiding complications
associated with deafferentation. The surgical goal is to identify and
mechanically isolate an irritating vessel from the cisternal segment of the
trigeminal nerve.
After the induction of general anesthesia, the patient is positioned
supine with the head turned away from the affected side and secured in pin
fixation, with the neck slightly flexed and elevated. The approximate
courses of the transverse and sigmoid sinuses are outlined on the scalp

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(Fig. 104.3). We place electrodes for auditory brainstem responses to
monitor for traction on the eighth cranial nerve. We have found facial
nerve monitoring unnecessary.

FIGURE 104.3 External landmarks for a left-sided microvascular decompression. The skin
incision (red line) is vertically oriented, passing from the top of the pinna down and behind the
mastoid tip. The transverse sinus can be approximated by a line connecting the zygoma to the inion.
A retrosigmoid craniotomy (black hashed line) is performed just below the junction of the
transverse and sigmoid sinuses.

The surgical field is shaved, prepped, and draped. We open a linear

incision two fingerbreadths behind the base of the pinna and extending
from the top of the pinna, over the digastric notch, and to the level of the
mastoid, pointing toward the ipsilateral foot (see Fig. 104.3). A pericranial
graft is harvested from above the nuchal line for later use in the dural
closure. The suboccipital musculature is dissected away, and a burr hole is
placed near the junction of the venous sinuses. We use a combination of
high-speed drilling and rongeur instruments to create an approximately 3-
cm craniotomy, exposing the edges of the transverse and sigmoid sinuses
superiorly and laterally, respectively. Mastoid air cells are waxed.
The dura is opened in a stellate manner. A handheld brain retractor is
used to depress the cerebellum, and CSF is aspirated from the cisterna
magna, slackening the hemisphere. Some surgeons place a lumbar drain at
the start of the case or perform a lumbar puncture intraoperatively.
The operating microscope is brought in, and under constant monitoring
of the auditory brainstem responses, a fixed retractor is used to displace

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the cerebellum from the lateral skull base (Fig. 104.4). We identify the
complex of the seventh and eighth nerves coursing out to the internal
auditory canal. A petrosal vein or venous complex usually obscures the
view of the (deeper) trigeminal nerve; this can be coagulated and divided
safely.

FIGURE 104.4 Intraoperative photographs from a left-sided microvascular decompression. Left

panel: Relevant anatomic structures visualized after dural opening and placement of a retractor on
the lateral cerebellum (C). From inferior to superior (left to right on the image): arachnoid
membranes overlying the complex of cranial nerves VII and VIII (white arrowhead), trigeminal
nerve (yellow asterisk), petrosal venous complex (blue triangle), and tentorium (T). Middle panel:
View of compression of the superior surface of the trigeminal nerve (yellow asterisk) by a loop of
the superior cerebellar artery (red arrowhead). Right panel: Teflon pledgets (black arrowheads) are
interposed between the trigeminal nerve and the artery.

Arachnoid adhesions are taken down sharply, and the trigeminal nerve
is traced to its entry zone in the lateral pons (see Fig. 104.4). The most
common offending vessel is the superior cerebellar artery (>80%), which
generally contacts the superomedial surface of the nerve. Other vascular
offenders may include the anterior inferior cerebellar artery and posterior
fossa veins. The segment of the nerve that is most sensitive to mechanical
irritation is the transition zone from central to peripheral myelin, which
occurs approximately 1 to 3 mm from the brainstem27,28; sometimes an
area of demyelination is visually apparent as a discolored patch on the
surface of the nerve.
A straight dissector is used to tease any offending vessel away from the
nerve. Teflon pledgets are interposed between the vessel and the nerve,
with care taken to ensure the vessel is not kinked in the process.
The cerebellar retractor is removed, and the field is irrigated. We close
the dura watertight using a pericranial graft. The duraplasty is coated with
a layer of fibrin glue, and the bony defect is corrected with bone cement or

5166
a titanium mesh. The soft tissue is closed in layers, culminating in an
absorbable stitch on the skin. Patients are monitored in the intensive care
unit for one night and usually discharge on the second postoperative day.
They are initially maintained on their baseline TN medication regimen,
which is then weaned later as an outpatient.

OUTCOMES
MVD offers excellent long-term pain control. Eighty percent to 96% of
patients experience initial pain relief after MVD.29–31 At 5 years, pain
control is maintained in 72% to 85%.31–33 One study with extended
follow-up reported that 73% of patients were pain free 15 years after
surgery.34
One of the landmark series of MVD for TN reports on the outcomes of
1,185 patients who underwent MVD over a 20-year period with outcomes
prospectively evaluated. At 10 years after surgery, 70% of patients were
pain free while off of medication.16 This study found that most recurrences
occur during the first 2 years after surgery, with very low recurrence rates
later.16
MVD has better outcomes in type 1 TN than type 2 TN perhaps because
patients with type 2 TN have greater underlying damage to the trigeminal
nerve.35 Presence of arterial compression of the nerve is also associated
with better outcomes,36 with greater degree of compression additionally
correlated with positive outcome.34 Treatment failure is associated with
longer symptom duration prior to surgery, presence of venous NVC, and
lack of immediate postoperative symptom relief.16
Although MVD has a higher complication rate than percutaneous
procedures, in experienced hands, the procedure is relatively safe.
Mortality is low (0.15% to 0.8%)37 and related to hospital and surgeon
volume.38 Trigeminal sensory deficit occurs in 1.6% to 22% of cases.29,33
The incidence of facial weakness is 1.2% to 6.8%.29,33 Hearing loss occurs
in 1.2% to 6.8% but may be decreased by the use of brainstem auditory
evoked potential monitoring.39
Other serious complications include cerebrospinal fluid leak (1.5% to
4%) and cerebellar infarct or hematoma (<1%).16,39 Anesthesia dolorosa is
very uncommon after MVD, with one large series reporting 0%

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incidence,16 although the rate may be higher with internal neurolysis, a
procedure involving the longitudinal splitting of trigeminal nerve fibers
that is sometimes used when NVC is not identified intraoperatively.32

Percutaneous Rhizotomy
Radiofrequency rhizotomy is an excellent surgical option for patients with
type 2 TN or for patients with type 1 TN who medically are not candidates
for MVD or have already failed MVD. The goal of a rhizotomy is to lesion
the retrogasserian trigeminal root, which can be accessed percutaneously
through the FO. The procedure is effective, can be performed on an
outpatient basis without general anesthesia, and can be repeated.
Drawbacks include facial numbness and the risk of deafferentation pain.
The patient is positioned supine on the operative table. Midazolam (1 to
2 mg) is administered for anxiolysis as well as meperidine (25 to 50 mg) to
blunt bradycardia that can occur with trigeminal stimulation. The head is
turned slightly away from the affected side, and submental vertex
fluoroscopy is used to identify the FO near the junction of the pterygoid
plate and the petrous ridge.
The face is prepped with alcohol and squared off with sterile towels.
Local anesthetic is instilled in the soft tissue along the anticipated needle
trajectory. The needle entry point is generally 2.5 cm lateral to and at or
just below the labial commissure. A 20G spinal needle is advanced toward
the FO, using the midpupil as an approximate external landmark.
Fluoroscopy is repeated when the needle contacts the skull base, and the
trajectory is adjusted until the FO is entered, which is often signified by a
jaw jerk and wince.
The fluoroscope is rotated into a lateral view. Under constant
fluoroscopy, the needle is advanced toward the clival line (Fig. 104.5). On
the lateral view, V2 fibers are encountered approximately at the clival line,
with V1 being deeper and V3 more superficial (see Fig. 104.5).
Radiofrequency rhizotomy is best reserved for cases of V2 or V3 TN; V1
fibers can be difficult to reach without a curved needle, and a
radiofrequency lesion risks corneal hypesthesia and resulting keratitis; for
these reasons, balloon compression is preferred for cases involving V1

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pain (see the following text).

FIGURE 104.5 Percutaneous radiofrequency rhizotomy, lateral view. Left panel: The gasserian
ganglion (GG) is located within Meckel’s cave. A spinal needle is used to pierce the foramen ovale,
and radiofrequency lesions are created in the retrogasserian fibers. V3 fibers are encountered
superficially, with V2 and V1 fibers deeper. Right panel: Lateral fluoroscopy demonstrating a
spinal needle passing through the foramen ovale (black arrowhead). The outline of the sella (S) can
be seen superiorly. V2 fibers are encountered at the clival line (white arrowheads).

The stylet is withdrawn and replaced with the radiofrequency probe.

Low-temperature stimulation (40° to 50° C) is delivered to confirm the
correct division has been targeted. Patients describe a burning sensation in
the corresponding sensory distribution. Propofol (2 to 4 mL) is
administered, and a radiofrequency lesion is delivered (60 seconds; 75° C
if at the clivus, 85° C if superficial to the clivus). We then withdraw the
needle ~2 to 3 mm and repeat this process iteratively, with the goal of
abolishing the patient’s ability to discriminate between pinprick and light
touch (usually two or three lesions per sensory division). When this is
achieved, the needle is withdrawn, and the patient is taken to the recovery
area.
Balloon compression is a percutaneous rhizotomy variant uniquely
indicated for V1 pain; the goal is to compress the trigeminal nerve within
the porus trigeminus. Surgical technique is similar to the radiofrequency
rhizotomy, except that it is typically done under general anesthesia and
requires a larger cannula (14G) to accommodate the balloon. A balloon
catheter is introduced after the FO has been cannulated, and it is advanced
on the lateral fluoroscopy view until the tip is just past the clival line. The
balloon is inflated to 1.5 atmospheres for 60 seconds before being
withdrawn.

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OUTCOMES
Percutaneous Radiofrequency Rhizotomy
Initial response to percutaneous radiofrequency rhizotomy is excellent,
with rates of pain relief up to 97.6%,40 on par with MVD. However, as
with other percutaneous procedures, the response to radiofrequency
rhizotomy is less durable, and the procedure may need to be repeated. One
of the largest series of radiofrequency rhizotomy followed the results of
1,600 patients with TN who underwent 2,138 radiofrequency rhizotomy
procedures over 25 years. This study found that 58% of patients who had
undergone a single procedure had complete pain relief at 5-year follow-up,
whereas 92% of patients achieved pain relief with multiple procedures at 5
years.40 At 20 years, 41% of patients who had undergone a single
procedure had pain relief, and all of the patients who had undergone
multiple procedures and were followed were free from pain.40
Type 1 TN may be associated with better outcomes following
radiofrequency rhizotomy,41 as is postoperative facial numbness.42 One of
the relative advantages of radiofrequency rhizotomy is that it allows more
selective targeting of specific trigeminal nerve distributions than chemical
or balloon rhizotomy.41
Radiofrequency rhizotomy has a higher rate of decreased corneal
sensation than other percutaneous procedures at 5.7% to 17.3%.40,43
Anesthesia dolorosa occurs in 0.8%.40 Higher lesioning temperatures may
be associated with higher rates of trigeminal sensory dysfunction.44
Masseter weakness occurs in 3% to 29% of cases.42 Some of the adverse
effects of radiofrequency rhizotomy are thought to occur via selective
damage to small unmyelinated trigeminal pain fibers.45

Percutaneous Balloon Compression

Percutaneous balloon compression similarly has a high rate of initial pain
control, with up to 94% reporting initial pain relief,46 with recurrence rates
of 20% to 48%.42 One of the largest published series reported on the
outcomes of 901 patients who underwent percutaneous balloon
compression at a single institution. This series found a 92.7% rate of
significant pain relief at 1 month, with excellent pain relief in 67.1% at 1
year and complete pain relief in 62% at mean 16.5 year follow-up.47

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 The rate of postoperative trigeminal sensory disturbance is high
following balloon compression, with initial disturbance in almost all
patients, and persistent symptoms in 4.6% to 40% of patients.37 Trigeminal
dysfunction may be related to the rate and duration of balloon
compression.48 Balloon compression has a low rate of decreased corneal
sensation, perhaps because it damages medium and large myelinated pain
fibers, sparing small fibers important in corneal sensation.45 As such, it is
the percutaneous treatment of choice for V1 distribution TN.
Conversely, the rate of masseter weakness following balloon
compression is high at 10% to 50%.42 Hearing loss is reported in 2.4% to
6.3%.49 And the rate of intraoperative trigeminal reflex bradycardia and
hypotension may be higher in balloon compression than other
percutaneous procedures, an important consideration for patients with
preexisting cardiac comorbidities.45

Radiosurgery
Radiosurgery uses focused radiation to the trigeminal nerve or ganglion to
disrupt pain transmission. Several different radiosurgery systems have
been used to treat TN. One of the most commonly used is Gamma Knife,
which uses 201 cobalt-60 radiation sources arranged in a hemispheric
assembly to target energy to a focal point. Linear accelerator–based
therapies have also been used in TN and generate high-energy particles
that are delivered through a single source that moves relative to the patient
around the planned focal point. One such system is CyberKnife, which
uses a linear accelerator mounted on a robotic arm, with two orthogonally
positioned x-ray detectors that provide movement correction by imaging
the patient’s bony anatomy.50 This system has also been used for TN with
success.50 All systems seem to have similar efficacy in TN.
During radiosurgery, the patient’s head is fixed using a head frame or
facemask, depending on the system being used. The patient’s MRI or CT
is used in conjunction with planning software to identify the target. Several
targeting strategies have been used, including a single isocenter in the
REZ,51 the cisternal portion of the trigeminal nerve,50,52 a retrogasserian
target in the anterior cisternal portion of the trigeminal nerve anterior to

5171
the emergence of the nerve,53,54 or two isocenters in the gasserian ganglion
and the REZ.55 One trial randomized patients to one versus two
retrogasserian isocenters and found that two isocenters did not improve
pain outcomes but resulted in a higher rate of sensory disturbances.56
Shorter distance between the target and brainstem may be associated with
better pain outcomes.57 Median doses of 70 to 90 Gy are generally
used.58,59 Higher dose rate may not only be associated with better initial
pain relief and lower recurrence rates59,60 but also be associated with
higher rates of trigeminal sensory dysfunction.60
One of the disadvantages of radiosurgery is that it has a delayed onset of
pain relief, with a median latency of 1 to 2 months,61 making it less
suitable for patients in acute pain crisis. A shorter latency to response may
predict longer durability of pain relief.62 Patients who undergo
radiosurgery early in their disease course have decreased latency to
response and longer durability of symptom relief.62

OUTCOMES
A high proportion of patients have at least some improvement in pain after
radiosurgery, with 79% to 92% reporting initial pain improvement.37
Unfortunately, durability and extent of pain relief are limited. Patients who
have not had previous surgery have better pain outcomes.54,63 Better
outcomes are also associated with type 1 TN, previous percutaneous
procedures, and older age.61,64 Interestingly, radiosurgery may also be
effective for MS-related TN.61
A large study reported on the outcomes of a series of 503 TN patients
treated with Gamma Knife. This study found that 89% of patients achieved
an initial Barrow Neurological Institute (BNI) pain score of I to IIIb (pain
adequately controlled with medication); this rate was 80% at 1 year, 46%
at 5 years, and 30% at 10 years.63 There was a 10.5% rate of new
trigeminal sensory disturbance.63 Another large study reported on 497
patients with type 1 TN not previously treated with radiosurgery and
followed for at least 1 year. This study reported that 92% had initial
freedom from pain, whereas at 5 and 10 years follow-up, 65% and 45% of
patients were pain free off medication, respectively.54
The most common side effect after radiosurgery is trigeminal sensory

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disturbance, with decreasing rates with increasing time after the
procedure.61 Higher radiation dose may be associated with greater rates of
sensory disturbance, ranging from 6% to 42%.37 Importantly,
postprocedure facial numbness is a predictor of treatment durability.61 The
rate of anesthesia dolorosa is very low (0.2%).63 Repeat radiosurgery is
associated with a higher rate of sensory dysfunction.65 Other, rarer
complications include masticator weakness and hearing loss.61
In patients who have recurrence of symptoms after initial radiosurgery,
repeat radiosurgery can provide symptom relief. One study found that 63%
of patients were pain free off medication at 1 year after repeat Gamma
Knife, whereas at 5 years, the rate had fallen to 37%.58 Response to initial
Gamma Knife and facial numbness after initial Gamma Knife were
predictors of response to repeat radiosurgery.58 Third Gamma Knife
procedure has also been reported in a small series, with 47% reporting
initial complete pain relief, and 35% maintaining this at mean 22.9 months
follow-up.66 There were no new sensory deficits after third Gamma
Knife.66

Conclusions
TN is a chronic facial pain disorder thought to stem from NVC of the
cisternal segment of the trigeminal nerve. There are two clinical variants:
type 1, consisting predominantly of brief, lancinating, or electrical pain,
and type 2, chiefly with constant burning or aching pain. Surgery should
be considered in patients’ refractory to carbamazepine or oxcarbazepine.
MVD remains the treatment of choice for type 1 TN, with excellent long-
term pain control—even in patients without radiographic NVC.
Radiofrequency rhizotomy is suitable for type 2 TN or patients with type 1
TN refractory to MVD or who are not suitable for a craniotomy.
Stereotactic radiosurgery offers more modest pain relief rates and effective
duration but is an excellent option for patients seeking to avoid an invasive
procedure.

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20. Smith KJ, McDonald WI. Spontaneous and mechanically evoked activity due to central
demyelinating lesion. Nature 1980;286:154–155.
21. Smith KJ, McDonald WI. Spontaneous and evoked electrical discharges from a central
demyelinating lesion. J Neurol Sci 1982;55:39–47.
22. Slavin KV, Nersesyan H, Colpan ME, et al. Current algorithm for the surgical treatment of
facial pain. Head Face Med 2007;3:30.
23. Sandell T, Eide PK. Effect of microvascular decompression in trigeminal neuralgia patients
with or without constant pain. Neurosurgery 2008;63:93–99; discussion 99–100.
24. Chun-Cheng Q, Qing-Shi Z, Ji-Qing Z, et al. A single-blinded pilot study assessing
neurovascular contact by using high-resolution MR imaging in patients with trigeminal
neuralgia. Eur J Radiol 2009;69:459–463.
25. Peker S, Dinçer A, Necmettin Pamir M. Vascular compression of the trigeminal nerve is a
frequent finding in asymptomatic individuals: 3-T MR imaging of 200 trigeminal nerves using

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26. Antonini G, Di Pasquale A, Cruccu G, et al. Magnetic resonance imaging contribution for
diagnosing symptomatic neurovascular contact in classical trigeminal neuralgia: a blinded
case-control study and meta-analysis. Pain 2014;155:1464–1471.
27. Donahue JH, Ornan DA, Mukherjee S. Imaging of vascular compression syndromes. Radiol
Clin North Am 2017;55:123–138.
28. Haller S, Etienne L, Kövari E, et al. Imaging of neurovascular compression syndromes:
trigeminal neuralgia, hemifacial spasm, vestibular paroxysmia, and glossopharyngeal
neuralgia. AJNR Am J Neuroradiol 2016;37:1384–1392.
29. Broggi G, Ferroli P, Franzini A, et al. Microvascular decompression for trigeminal neuralgia:
comments on a series of 250 cases, including 10 patients with multiple sclerosis. J Neurol
Neurosurg Psychiatry 2000;68:59–64.
30. Pamir MN, Peker S. Microvascular decompression for trigeminal neuralgia: a long-term
follow-up study. Minim Invasive Neurosurg 2006;49:342–346.
31. Tyler-Kabara EC, Kassam AB, Horowitz MH, et al. Predictors of outcome in surgically
managed patients with typical and atypical trigeminal neuralgia: comparison of results
following microvascular decompression. J Neurosurg 2002;96:527–531.
32. Ko AL, Ozpinar A, Lee A, et al. Long-term efficacy and safety of internal neurolysis for
trigeminal neuralgia without neurovascular compression. J Neurosurg 2015;122:1048–1057.
33. Pollock BE, Stien KJ. Posterior fossa exploration for trigeminal neuralgia patients older than
70 years of age. Neurosurgery 2011;69:1255–1260.
34. Sindou M, Leston J, Decullier E, et al. Microvascular decompression for primary trigeminal
neuralgia: long-term effectiveness and prognostic factors in a series of 362 consecutive
patients with clear-cut neurovascular conflicts who underwent pure decompression. J
Neurosurg 2007;107:1144–1153.
35. Degn J, Brennum J. Surgical treatment of trigeminal neuralgia. Results from the use of
glycerol injection, microvascular decompression, and rhizotomia. Acta Neurochir (Wien)
2010;152:2125–2132.
36. Miller JP, Acar F, Burchiel KJ. Classification of trigeminal neuralgia: clinical, therapeutic,
and prognostic implications in a series of 144 patients undergoing microvascular
decompression. J Neurosurg 2009;111:1231–1234.
37. Bick SKB, Eskandar EN. Surgical treatment of trigeminal neuralgia. Neurosurg Clin N Am
2017;28:429–438.
38. Kalkanis SN, Eskandar EN, Carter BS, et al. Microvascular decompression surgery in the
United States, 1996 to 2000: mortality rates, morbidity rates, and the effects of hospital and
surgeon volumes. Neurosurgery 2003;52:1251–1262.
39. McLaughlin MR, Jannetta PJ, Clyde BL, et al. Microvascular decompression of cranial
nerves: lessons learned after 4400 operations. J Neurosurg 1999;90:1–8.
40. Kanpolat Y, Savas A, Bekar A, et al. Percutaneous controlled radiofrequency trigeminal
rhizotomy for the treatment of idiopathic trigeminal neuralgia: 25-year experience with 1,600
patients. Neurosurgery 2001;48:524–534.
41. Jin HS, Shin JY, Kim YC, et al. Predictive factors associated with success and failure for
radiofrequency thermocoagulation in patients with trigeminal neuralgia. Pain Physician
2015;18:537–545.
42. Wang JY, Bender MT, Bettegowda C. Percutaneous procedures for the treatment of trigeminal
neuralgia. Neurosurg Clin N Am 2016;27:277–295.
43. Fraioli B, Esposito V, Guidetti B, et al. Treatment of trigeminal neuralgia by
thermocoagulation, glycerolization, and percutaneous compression of the gasserian ganglion
and/or retrogasserian rootlets: long-term results and therapeutic protocol. Neurosurgery

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44. Tronnier VM, Rasche D, Hamer J, et al. Treatment of idiopathic trigeminal neuralgia:
comparison of long-term outcome after radiofrequency rhizotomy and microvascular
decompression. Neurosurgery 2001;48:1261–1268.
45. Cheng JS, Lim DA, Chang EF, et al. A review of percutaneous treatments for trigeminal
neuralgia. Neurosurgery 2014;10(suppl 1):25–33.
46. Lobato RD, Rivas JJ, Sarabia R, et al. Percutaneous microcompression of the gasserian
ganglion for trigeminal neuralgia. J Neurosurg 1990;72:546–553.
47. Abdennebi B, Guenane L. Technical considerations and outcome assessment in retrogasserian
balloon compression for treatment of trigeminal neuralgia. Series of 901 patients. Surg Neurol
Int 2014;5:118.
48. Abdennebi B, Bouatta F, Chitti M, et al. Percutaneous balloon compression of the Gasserian
ganglion in trigeminal neuralgia. Long-term results in 150 cases. Acta Neurochir (Wien)
1995;136:72–74.
49. de Siqueira SR, da Nobrega JC, de Siqueira JT, et al. Frequency of postoperative
complications after balloon compression for idiopathic trigeminal neuralgia: prospective
study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:e39–e45.
50. Karam SD, Tai A, Snider JW, et al. Refractory trigeminal neuralgia treatment outcomes
following CyberKnife radiosurgery. Radiat Oncol 2014;9:257.
51. Hitchon PW, Holland M, Noeller J, et al. Options in treating trigeminal neuralgia: experience
with 195 patients. Clin Neurol Neurosurg 2016;149:166–170.
52. Martinez Moreno NE, Gutierrez-Sarraga J, Rey-Portoles G, et al. Long-term outcomes in the
treatment of classical trigeminal neuralgia by Gamma Knife radiosurgery: a retrospective
study in patients with minimum 2-year follow-up. Neurosurgery 2016;79:879–888.
53. Park SC, Kwon DH, Lee DH, et al. Repeat Gamma-Knife radiosurgery for refractory or
recurrent trigeminal neuralgia with consideration about the optimal second dose. World
Neurosurg 2016;86:371–383.
54. Regis J, Tuleasca C, Resseguier N, et al. Long-term safety and efficacy of Gamma Knife
surgery in classical trigeminal neuralgia: a 497-patient historical cohort study. J Neurosurg
2016;124:1079–1087.
55. Dai ZF, Huang QL, Liu HP, et al. Efficacy of stereotactic Gamma Knife surgery and
microvascular decompression in the treatment of primary trigeminal neuralgia: a retrospective
study of 220 cases from a single center. J Pain Res 2016;9:535–542.
56. Flickinger JC, Pollock BE, Kondziolka D, et al. Does increased nerve length within the
treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind,
randomized study. Int J Radiat Oncol Biol Phys 2001;51:449–454.
57. Massager N, Lorenzoni J, Devriendt D, et al. Gamma Knife surgery for idiopathic trigeminal
neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J
Neurosurg 2004;100:597–605.
58. Helis CA, Lucas JT Jr, Bourland JD, et al. Repeat radiosurgery for trigeminal neuralgia.
Neurosurgery 2015;77:755–761.
59. Lee JY, Sandhu S, Miller D, et al. Higher dose rate Gamma Knife radiosurgery may provide
earlier and longer-lasting pain relief for patients with trigeminal neuralgia. J Neurosurg
2015;123:961–968.
60. Pollock BE, Phuong LK, Foote RL, et al. High-dose trigeminal neuralgia radiosurgery
associated with increased risk of trigeminal nerve dysfunction. Neurosurgery 2001;49:58–64.
61. Wolf A, Kondziolka D. Gamma Knife surgery in trigeminal neuralgia. Neurosurg Clin N Am
2016;27:297–304.
62. Mousavi SH, Niranjan A, Huang MJ, et al. Early radiosurgery provides superior pain relief for

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63. Kondziolka D, Zorro O, Lobato-Polo J, et al. Gamma Knife stereotactic radiosurgery for
idiopathic trigeminal neuralgia. J Neurosurg 2010;112:758–765.
64. Taich ZJ, Goetsch SJ, Monaco E, et al. Stereotactic radiosurgery treatment of trigeminal
neuralgia: clinical outcomes and prognostic factors. World Neurosurg 2016;90:604.e11–
612.e11.
65. Tuleasca C, Carron R, Resseguier N, et al. Decreased probability of initial pain cessation in
classic trigeminal neuralgia treated with Gamma Knife surgery in case of previous
microvascular decompression: a prospective series of 45 patients with >1 year of follow-up.
Neurosurgery 2015;77:87–95.
66. Tempel ZJ, Chivukula S, Monaco EA III, et al. The results of a third Gamma Knife procedure
for recurrent trigeminal neuralgia. J Neurosurg 2015;122:169–179.

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CHAPTER 105
Ablative Neurosurgical Procedures
for Chronic Pain
BENJAMIN L. GRANNAN, MUHAMED HADZIPASIC,
and EMAD N. ESKANDAR

Consideration of an ablative procedure for chronic pain typically follows

numerous evaluations for other therapeutic options that have either failed
or were deemed not suitable for the patient. The decision tree for deciding
a patient’s candidacy for surgical ablation hinges on careful consideration
of the type of pain present, its mechanism, the anatomic distribution, the
desired durability of a cure, and the overall state of health and life
expectancy of the patient. This clinical information is then merged with
our current framework and understanding of pain signaling pathways to
develop a treatment plan with the highest probability of achieving the
patient-specific metric for success. The efficacy of ablative procedures
depends heavily on our understanding of the physiology of the human pain
experience incorporating all elements beginning with the nature of the
peripheral stimulus end ending with behavioral and emotional perception
of pain. Current theory has evolved from concepts of serial processing
defining the “labelled line” theory of pain transmission to more
sophisticated, distributed models of a “pain matrix,” in which peripheral
nociception feeds into multilayered central circuitry that not only localizes
painful stimuli but also incorporates emotional and temporal contexts,
elicits top–down control, and changes the way future stimuli are
perceived.1 Ablative procedures seek to alter pain processing by removing
part of this complex circuitry (Fig. 105.1). In doing so, it is possible to
disrupt pain transmission but also to change how it is processed—
sometimes leading to initial pain relief followed by recurrence. Because
neuroaugmentative procedures incorporating high-frequency stimulation
and local analgesic administration have become routine parts of clinical

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practice, use of neuroablative techniques has decreased. However, several
procedures still provide significant value in certain clinical scenarios. In
this chapter, we review the indications, anatomy, techniques, and
outcomes in dorsal root entry zone lesioning, cordotomy, stereotactic
cingulotomy, thalamotomy, and tractotomies within the brainstem.

FIGURE 105.1 Specific ablative lesions and their locations relative to the nociceptive pathways.

Dorsal Root Entry Zone Lesioning

INDICATIONS
Lesioning of the dorsal root entry zone of the spinal cord (DREZ
procedure) is performed in patients with refractory neuropathic pain of
peripheral origin, most commonly resulting from nerve root avulsion or
injury within the brachial plexus. The procedure has also been performed
in neuropathic pain resulting from spinal cord injury (SCI), spasticity, and
postherpetic neuralgia.2,3 Although less typical, it has also been performed
in patients suffering cancer-related pain. Because the DREZ procedure
disrupts afferent pain signaling at a specific level, patients with pain
distributions that are focal, only spanning a few dermatomal levels, are
considered better candidates for this procedure compared to individuals
with more diffuse pain syndromes.4

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ANATOMY AND PHYSIOLOGY
The DREZ procedure is built on the hypothesis that following injury of
primary peripheral neurons and subsequent deafferentation, central
second-order neurons in the spinal cord become hypersensitive and
produce aberrant afferent pain signals. This occurs in the absence of a real
painful stimulus and is therefore neuropathic in nature. The cell bodies of
the second-order sensory neurons carrying afferent pain information reside
in the substantia gelatinosa (Rexed layers 1 and 2) of the dorsal horn
throughout the spinal cord.3 Primary neurons, whose cell bodies reside in
the dorsal root ganglion, enter the spinal cord via the DREZ and either
immediately synapse in the substantia gelatinosa or travel within
Lissauer’s tract 1 to 2 levels above or below the level of entry prior to
synapsing.5 The area of synapse lies immediately deep and medial to the
entry zone where nerve rootlets enter the spinal cord (Fig. 105.2).
Lesioning this area disrupts the abnormal pain signaling of second-order
neurons at the associated dermatomal level but does not affect
transmission of painful stimuli arising from levels below the lesion that
travel within the spinothalamic tract. This is in contrast to cordotomy
which specifically targets the ascending spinothalamic tract, thus severing
pain transmission of all dermatomal levels whose second-order neurons
have already entered and are traveling in the spinothalamic tract. It is
important to recognize that the corticospinal tract lies lateral to the dorsal
horn and ablations targeted too laterally can result in ipsilateral
hemiparesis. Additionally, in cervical levels of the spinal cord,
proprioceptive information from the ipsilateral arm runs in the dorsal
column just medial to the dorsal horn. Therefore, lesioning aimed too far
medially may result in loss of ipsilateral upper extremity proprioception.5,6

TECHNIQUE
Under general anesthesia, the patient is placed in the prone position with
rigid head fixation. Multiple laminotomies are made to provide adequate
access to the spinal cord level of interest and one to two spinal cord levels
above and below. A midline durotomy is performed, and the posterolateral
sulcus on the affected side is identified. In instances of nerve root or
brachial plexus injury, nerve root atrophy can often be observed and used

5180
to identify the appropriate level for lesioning. This can be confirmed after
placing the radiofrequency ablation (RFA) probe (e.g., Nashold electrode)
in the DREZ and measuring an impedance value between the DREZ of the
spinal cord and a peripherally placed grounding electrode. Injured areas
have markedly decreased impedance values. This measurement will also
serve as a preablation baseline (typically 900 to 1,200 ohms) because the
impedance will also decrease after lesioning is performed. To perform the
ablation, the Nashold electrode is placed 1 to 2 mm into the area of the
entry zone at an angle 20 to 30 degrees medial to lateral relative to the
plane perpendicular to the spinal cord surface.7 Each RFA is then carried
out by powering to a temperature of 75° C for 15 to 20 seconds. A total of
40 to 60 lesions centered around the level of interest are performed.8
Microsurgical technique as well as laser ablation serve as alternatives to
RFA.

OUTCOMES
Patients experiencing the most favorable outcomes following the DREZ
procedure are those suffering from neuropathic pain related to brachial
plexus avulsion injury. A review of the published clinical studies that
reported greater than 20 patients identified 62% to 91% patients suffering
from brachial plexus avulsion pain to have “good improvement” in
symptoms after the surgery,9–13 where “good improvement” was defined
as the need for only minimal ongoing medical management to maintain
satisfactory pain relief.5 The knowledge surrounding the durability of pain
control is limited by the length of follow-up in the published studies but
has been confirmed to last, in some instances, up to 3 to 5 years. One
particular study performed a subgroup analysis to evaluate the effect of
intraoperative electrophysiology mapping of the DREZ on outcome and
found improved pain control in the group that received intraoperative
mapping.12 Patients undergoing DREZ for SCI-related pain can expect
pain relief of localized, end-zone pain occurring just at or above the level
of sensory loss. More diffuse and distal pain phenomenon below the level
of injury, however, is not as well managed, with efficacy rates falling to
20% or lower.5 To improve efficacy of the DREZ procedure in SCI
patients, Falci et al.14 have suggested using intramedullary

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electrophysiologic guidance to identify regions of spontaneous DREZ
hyperactivity to identify optimal lesion placement. In a group of 32
patients who underwent this approach, 84% achieved 100% pain
reduction. Pain control following the DREZ procedure in patients suffering
from postherpetic neuralgia is felt to be only transient, with only
approximately 25% of patients experiencing relief at 1 year.2 Outcomes
are largely comparable for RFA versus laser or microsurgical technique.15
However, many surgeons utilize the RFA technique because of the
reproducible lesions provided by the Nashold electrode.5
The most common adverse effect of the DREZ procedure is paresthesia,
which is usually transient but can be permanent in a minority of cases.
This is estimated to incidence of transient or permanent paresthesias, that
is, 15% to 30%.4 Transient or temporary motor weakness is also a known
risk of the procedure which results from an ablation field that extends
laterally beyond the DREZ to involve the corticospinal tract. Incidence
rates of permanent weakness vary widely, with the majority of studies
citing less than 10% risk, with some studies citing up to 40% to 60%
according to a review by Konrad.5

Cordotomy
INDICATIONS
Destruction of the anterolateral column, or spinothalamic tract, for
treatment of chronic pain, was first reported in 1912 by Spiller and
Martin.16 The procedure, referred to as cordotomy, has evolved since that
time but exists today in its same conceptual form, with the goal of
eliminating the transmission of afferent pain signal by ablating the
spinothalamic tract. The most appropriate candidates are those who have
localized, unilateral pain that is nociceptive in origin.17 The most typical,
current-day indication would be in the setting of intractable unilateral
pelvic, flank, or chest wall pain from metastatic cancer. Cordotomy has
become less commonly performed due to the rise of opioid therapies and
intrathecal pain pumps for palliation but should continue to be considered
in situations in which these initial therapies are ineffective or inappropriate
in the setting of the patient’s wishes or life expectancy. Additionally, it is

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important to note that chronic cancer-related pain can develop a
neuropathic component due to actual injury to nerve fibers, and it is
important to counsel patients regarding the likely persistence of the
neuropathic component after cordotomy.17 The surgery is either performed
percutaneously at the C1/2 level with the patient awake to provide sensory
feedback or via an open surgical approach at an upper thoracic level with
the patient under general anesthesia in the prone position. For
percutaneous cervical technique, the patient must be able to tolerate lying
flat and still for approximately 45 minutes. For thoracic open cordotomy,
the patient must not have other active cardiac, pulmonary, or hematologic
medical problems that would contraindicate an open surgery in the prone
position.18

ANATOMY AND PHYSIOLOGY

The anatomic target of the cordotomy is the spinothalamic tract within the
anterolateral quadrant of spinal cord at the high cervical level (C1/2) or
mid-to-upper thoracic level (T4) on the side contralateral to the patient’s
pain.19,20 Pain-mediating afferent fibers enter the spinal cord through the
DREZ on the side of the painful stimulus before synapsing in the
substantia gelatinosa of the dorsal horn and decussating via the anterior
commissure and joining the ascending fibers of the spinothalamic tract
contralateral to the side of pain. The decussation of fibers for a given nerve
root entry level can occur over 2 to 5 spinal levels.17 Therefore, the
cordotomy lesion ought to be sufficiently rostral relative to the level of
pain in order to fully disrupt nociceptive transmission. As general rule of
thumb, allowing for per-patient variation, a C1/2 cordotomy tends to result
in analgesia at C5 and below, whereas a T4 cordotomy will achieve
analgesia at T10 and below.20 The somatotopic arrangement of the
spinothalamic tract lends itself to targeted lesioning when percutaneous
RFA is performed. The ascending spinothalamic tract accrues fibers
decussating from their contralateral entry at its medial-most aspect. This
leads to the sacral representation being most dorsal, and lateral and the
cervical representation being most ventral and medial, with lumbar and
thoracic information arranged accordingly in between. This somatotopy is
demonstrated in Figure 105.2.

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FIGURE 105.2 Schematic of cervical and thoracic spinal cord lesions for pain including (A)
dorsal root entry zone (DREZ), (B) percutaneous cervical cordotomy, and (C) open thoracic
cordotomy in axial cross-section. In panes A and B, the somatopic arrangement of the
spinothalamic tract is shown. Ablations are depicted in orange. DREZ is performed on the side
ipsilateral to the pain, whereas cordotomy is performed on the side contralaterally. Percutaneous
cordotomy lesion is made with thermal exposed tip electrode, and open cordotomy is made with an
angled cordotomy blade. CST, corticospinal tract; DC, dorsal columns; DL, dentate ligament;
DSCT, dorsal spinocerebellar tract; LT, Lissauer’s tract; STT, spinothalamic tract; VSCT, ventral
spinocerebellar tract.

As a result, in patients with predominant hemipelvis or unilateral lower

extremity pain, it is possible to selectively lesion sacral and lumbar fibers
while preserving the cervical and thoracic domains of the spinothalamic
tract.17
The operating surgeon must be keenly aware of critical structures in
near proximity to the lesion target. Anterior horn cells controlling level-
specific motor function lie deep and medial to the spinothalamic tract
throughout the spinal cord and are at risk of being involved in the field of
ablation. Therefore, C1/2 and midthoracic levels are preferred because loss
of anterior horn cells at these levels is not associated with significant
morbidity. However, high cervical lesions near the cervicomedullary
junction can involve decussating fibers of the cortical spinal tract and pose
the risk of causing contralateral weakness of the lower extremity.
Importantly, interneurons involved in respiratory control reside within the

5184
upper cervical levels and are located within the ventromedial cord in near
proximity to the spinothalamic tract. Because of this, bilateral cervical
cordotomies must be judiciously considered in order to avoid the life-
threatening sleep-related apnea phenomenon, commonly referred to as
Ondine’s curse.17

TECHNIQUE
Percutaneous cervical cordotomy is performed under either fluoroscopic21
or computed tomography (CT)-guidance.17 The patient is placed in the
supine position with the head maintained in slight flexion either with a
fixation band or rigid frame fixation depending on surgeon preference. A
combination of local anesthetic and light sedation is provided for
anesthesia. The C1/2 interspace is identified using lateral x-ray or CT
imaging. In the case of fluoroscopy or x-ray technique, a 20-gauge spinal
needle must first be introduced into the subarachnoid space in order to
inject contrast to aid in identification of the dentate ligament, which is the
critical landmark in the anterior-posterior dimension for safe localization
of the spinothalamic tract. CT myelogram with contrast injection through
either lumbar or cervical site provides multiplanar acquisition of imaging
to more confidently identify the needle or cannula trajectory with respect
to the dentate ligament and spinothalamic tract. Once the dentate ligament
is identified, the electrode cannula with stylet is introduced into the spinal
cord with a goal target of 1 to 2 mm anterior to the dentate ligament for
sacral and lumbar fibers and 2 to 3 mm anterior to the ligament for
thoracic and cervical fibers. Repeat CT imaging may be obtained to
confirm appropriate cannula positioning. The stylet is then removed, and
the noninsulated electrode (2.5 mm in length by 0.25 mm in diameter) is
introduced into the spinal cord through the cannula. The electrode
impedance is tested to confirm intraparenchymal placement (greater than
800 ohms).17,21 Stimulation of 0.2 to 1.5 mV can be provided at 100 Hz to
obtain neurophysiologic confirmation of electrode placement. The patient
will likely experience dysesthesias in the form of inappropriate
temperature sensation. Once there is satisfactory confirmation of correct
electrode positioning, ablation is performed by heating the tissue to 70° C
to 80° C for 60 seconds. Depending on the extent of the patient’s pain

5185
symptoms, multiple lesions may be performed. Postprocedurally, the
patient is monitored closely either in perioperative recovery unit or in the
intensive care unit for at least 4 to 6 hours prior to less intensive
monitoring or discharge.
Open thoracic cordotomy is performed in the operating room with the
patient in the prone position. A bilateral or hemilaminectomy is performed
and a durotomy is made to provide access and direct visualization of the
spinal cord. The dentate ligament is identified and separated from the dura
to facilitate gentle upward rotation of the spinal cord to provide the
surgeon access to the anterior spinal cord. An angled cordotomy knife is
then inserted anterior to the dentate ligament to a depth of 3 to 4 mm and
swept anteriorly to ensure complete disruption of the spinothalamic tract.
It is essential that the surgeon respect the dentate ligament as the posterior
boundary in order to avoid injury to the corticospinal tract.5 The dura is
then closed in a watertight fashion in order to prevent cerebrospinal fluid
(CSF) leak. Figures 105.2b and 105.2c demonstrate the differences in
approach and the expected lesion size for percutaneous and open
cordotomy. Of note, the ventral spinocerebellar tract is more likely to be
involved in the open lesion which may contribute to postoperative ataxia.

OUTCOMES
Compared to other ablative procedures for pain, cordotomy is well studied
with over 3,600 patients reported in the literature, including one
prospective study.22 In general, as reviewed by Konrad,5 immediate pain
relief following percutaneous cordotomy occurs in approximately 90% of
patients with rates of pain relief falling to 50% to 60%, 1 year after
procedure. Similarly, open cordotomy provides high rates of immediate
pain relief (up to 93% reported by Cowie and Hitchcock23) which fall to
54% to 65% after 1 year follow-up.23–25 Therefore, cordotomy remains an
impactful option for patients with severe pain due to advanced metastatic
disease. Its efficacy has also been studied in cases of chronic pain from
nonmalignant etiologies. In a study of 122 patients who underwent
percutaneous cervical cordotomy, 27 suffered from nonmalignant sources
of pain. In this subgroup, only 20% experienced complete pain relief
compared to a rate of 66% in cancer patients. Cordotomy, therefore, is felt

5186
to be most effective for cancer-related pain but still remains an option for
patients suffering from intractable pain due to SCI or other etiologies, in
which all other options have been exhausted.
The most common adverse outcomes reported following cordotomy
include spinal headache from dural puncture, short duration of “mirror
pain” during which time symptoms similar to preoperative pain are
experienced on the contralateral side of the body, dysesthesias, ataxia,
temporary leg weakness, and temporary bowel and/or bladder
dysfunction.18 Estimated incidences of these side effects are reported to be
in the range of 10% to 34%, with ataxia and bladder dysfunction being
most commonly reported. Serious adverse events including respiratory
impairment and even associated death have been reported even in
unilateral procedures. Ischia et al.26 cites a 0% to 9% risk of mortality rate
in unilateral procedures and 11% risk of death in bilateral cervical
cordotomy. It is generally felt that the majority of complications arise from
poor electrode placement and that the rise of CT guidance has led to
decreased rates of severe complication.17 Open cordotomy comes with the
increased risk of CSF leak due to larger durotomy, but the ablation-related
neurologic side effects discussed are largely similar in both percutaneous
and open approaches.5

Cingulotomy
INDICATIONS
Although cingulotomy was first performed for psychiatric disease by Sir
Hugh Cairns in 1948, it was not until over a decade later in that the first
series on cingulotomy for intractable pain was reported in 1962 by Foltz
and White at the University of Washington.27,28 Motivated by significant
reduction of intractable pain in patients who had undergone prefrontal
lobotomy in combination with animal studies implicating the frontal
cingulum fasciculus as the critical white matter tract involved generating
the emotional valence of pain,29–31 Foltz and White28 sought to employ
stereotactic cingulotomy as a refined ablative approach for pain control.
Rather than enrolling patients based on a specific etiology of intractable
pain, they worked with psychiatry colleagues to select patients who

5187
“showed prominent emotional factors” such that the cingulotomy might
“modify the patient’s emotional response . . . so that his expressions of fear
and anxiety no longer augmented critically whatever pattern of organic
pain was present.”28 Following their initial success with their report
describing 11 of 16 patients experiencing good pain relief, many other
groups explored the role of anterior cingulotomy for chronic medically
refractory pain, including applications for both neoplastic and
nonneoplastic sources of pain. In recent years, however, the rise of
implantable intrathecal pain pumps and neuromodulatory devices, anterior
cingulotomy has become less popular.32 However, anterior cingulotomy
continues to offer a widely applicable approach for severe, intractable
pain, especially in patients predominantly featuring an affective
component to their pain. It may also be most appropriate in patients who
are not candidates for implantable devices due to barriers to frequent
follow-up care or due to short life expectancy in the setting of end-stage
malignancy.

ANATOMY AND PHYSIOLOGY

General pain perception has been described as being divided into two
components: a lateral pain system involved in spatial discrimination of
pain and a medial pain system involved in the affective and autonomic
response to pain.33 The anterior cingulate is a main component of the
medial system. It is located mesial, ventral, rostral, and dorsal relative to
the genu of the corpus callosum and has broad connections to many
different sites involved in pain processing. These include the medial
frontal cortex, thalamic nuclei (anterior, midline, interlaminar, and others),
septum, amygdala, basal ganglia, nucleus accumbens, and brain stem sites
such as the periaqueductal gray.34 The anterior cingulate receives
nociceptive input and has connections with several sites involved in the
affective and attentional component of pain which is supported by a broad
range of data. Foltz and White,28 for example, noted changes in comfort
and affect in several patients immediately following lesioning in the
operating room. Additionally, functional imaging studies have shown
bilateral response within the anterior cingulate in response to pain.35
Furthermore, intraoperative single neuron recordings in humans

5188
undergoing anterior cingulotomy for psychiatric disease have
demonstrated modulated activity in response to thermal and mechanical
noxious stimuli. Those same neurons did not respond to nonnoxious
stimuli.36 Furthermore, stimulation studies in monkeys and humans have
been able to induce responses of fear or happiness in response to anterior
cingulate stimulation.33

TECHNIQUE
When the procedure was first developed in the 1950s prior to CT and
magnetic resonance imaging (MRI) availability, ventriculography was
used for anterior cingulate localization relative to the frontal horn of the
lateral ventricle. The lesion was frequently performed with the patient
awake to allow for continuous assessment of the patient’s emotional,
affective, and motor function.28 In current practice, the procedure is
performed with either under CT- or MRI-based stereotactic guidance, with
MRI becoming progressively more popular. The bilateral anterior
cingulate targets are mapped preoperatively with standard coordinates
being 20 to 25 mm posterior to tip of frontal horn, 7 mm lateral from
midline, and 2 to 3 mm superior to the corpus callosum.37 Importantly, two
retrospective analyses of patients with lesions ranging from 17.5 mm to
37.5 mm posterior from the tip of the frontal horn showed that patients
with more posterior lesions had less effective pain relief.32,38 In the
operating room, the target is accessed through the placement of two burr
holes, each approximately 20 to 30 mm from midline just anterior to the
coronal suture. Correct stereotactic placement can be confirmed by the use
of microelectrode recording. An uninsulated 10-mm radiofrequency
thermocoagulation electrode is placed in the target tissue which is then
heated to 85° C for 90 seconds. Typically, the electrode is then pulled back
5 mm, and a second lesion is made.37 Multiple lesions along the cingulate
cortex in the anterior-posterior direction can be performed. Figure 105.3
provides postoperative MRI demonstrating ablation of the bilateral anterior
cingulate cortex with three lesions on each side. Alternative methods for
creating the lesion include radiofrequency thermal ablation and laser
interstitial thermal therapy.

5189
FIGURE 105.3 Postoperative magnetic resonance imaging following stereotactic anterior
cingulotomy. A: Sagittal T1 sequence reveals three lesions (white arrow) within the anterior
cingulate gyrus. B: Coronal postcontrast T1 sequence shows bilateral lesions within the anterior
cingulate gyrus with postsurgical changes along the stereotactic probe trajectories through the
bilateral frontal calvarium and frontal lobes.

OUTCOMES
Anterior cingulotomy has generally been referred to as an option most
appropriate for patients suffering from cancer-related nociceptive pain.
However, a recent review and meta-analysis by Sharim and Pouratian32
showed equivalent outcomes in both neoplastic and nonneoplastic
populations. In a total of 224 patients (97 with cancer-related pain and 127
with noncancer pain) across 11 studies, 66.5% reported pain relief after the
procedure. This rate was comparable in both cancer patients (65.3%) and
noncancer patients (68.0%). Table 105.1, adapted from their review,
contains the breakdown of the outcomes on a per study basis. Types of
noncancer pain varied widely including neurofibromatosis, thalamic
stroke, trauma, failed back syndrome, phantom limb pain, atypical facial
pain, and peripheral neuropathy.32

TABLE 105.1 Outcomes of Anterior Cingulotomy Broken Down by

Neoplastic versus Nonneoplastic Pain Etiology
Total Fraction (%) Experiencing Pain Relief
No. of
Study Patients Cancer Noncancer
Foltz and White28 16 5/6 (83) 6/10 (60)

5190
 Foltz and White64 35 9/11 (82) 18/24 (75)

Faillace et al.65 9 3/7 (43) 1/2 (50)

Hurt and Ballantine66 68 18/32 (56) 16/36 (44)

Voris and Whisler67 16 5/5 (100) 8/11 (73)

Pillay and Hassenbusch68 10 5/8 (63) 1/2 (50)

Cohen et al.39 12 — 8/12 (67)

Wilkinson69 23 — 18/23 (78)

Yen et al.70 22 12/15 (80) 7/7 (100)

Yen et al.40 10 6/10 (60) —

Patel et al.71 3 3/3 (100) —

TOTAL 224 66/97 (68) 83/127 (65)
Modified from Sharim J, Pouratian N. Anterior cingulotomy for the treatment of chronic intractable
pain: a systematic review. Pain Physician 2016;19:537–550.

Although up to two-thirds of patients will report pain relief at some

point postoperatively, the durability of the relief has been shown to
diminish with time. In some instances of persistent pain in the immediate
postoperative period, repeat cingulotomy is offered in order to expand the
extent of the lesion. The incidence of repeat cingulotomy has been
estimated at 7.6% across all published cases32; however, the current
routine addition of a second ablative site after withdrawing the ablative
catheter 5 mm is thought to mitigate this risk.
Temporary postoperative adverse symptoms associated with
cingulotomy include urinary incontinence, confusion, and disorientation.
More serious reported events include a less than 5% incidence seizure and
less than 1% incidence of hemiparesis or personality change.32 Longer
term assessment of effect on cognition have revealed decrements in
executive function that peaks in severity at approximately 3 months
postoperatively but tends to resolve by 1 year postprocedure. Persistent
impairment in spontaneous word production and speech fluency have also
been reported.39,40

Thalamotomy
INDICATIONS
The thalamus is a collection of nuclei through which nearly all sensory

5191
input passes in order to reach the cortex and conscious perception. As
such, the thalamus was recognized early as a logical target for disrupting
nociceptive transmission through anatomically precise ablative
procedures.41,42 However, early experience with thalamic lesioning for
chronic pain forced a reconsideration of the thalamus as a simple relay
station because therapeutic pain relief achieved by thalamotomy frequently
waned within 3 to 6 months of the procedure.43 These observations,
combined with other unwanted sensory and psychiatric side effects, and
the advent of more sophisticated pharmacologic and deep brain stimulation
procedures for chronic pain control have led to a general paucity of
rigorous clinical data assessing the efficacy of thalamotomy. It is currently
a relatively rare procedure used for chronic, nonmalignant pain and is
considered a last-line approach for malignant neuropathic pain.22 Most
typically, it is used in scenarios of limited life expectancy where direct
tumor invasion is causing intractable face and/or head pain that is not
alleviated by pharmacologic therapy and is not anticipated to be
adequately managed by an ablative lesion at the spinal cord or peripheral
level. Thalamic targets have evolved from lateral to medial with the
observation that ventrocaudal thalamic nucleus lesions tend to produce
more unwanted side effects.44,45 Currently, medial targets including
centromedian (CM), parafascicular (PF), and centrolateral (CL) are most
common, with the pulvinar nucleus also being targeted.46 Recently, with
the emergence of focused ultrasound (FUS) as a technique for achieving
precise ablation, thalamotomy is being revisited as a method for treatment
of nonmalignant chronic neuropathic pain.47 As results using this method
become more established and as refinement of FUS technique occurs,
reconsideration of thalamic targets for ablation in specific clinical
scenarios may be warranted.

ANATOMY AND PHYSIOLOGY

Thalamic nuclei are anatomically organized into medial, lateral, and
anterior groups separated internally by the internal medullary lamina
(which houses intralaminar nuclei) and contained laterally by the thalamic
reticular nucleus.48 Additional functional characterization of nuclei exists
based on the origin of their inputs as well as the specificity of their

5192
projections. Medial nuclei receiving peripheral nociceptive inputs include
the dorsomedial nucleus (DM), which primarily receives inputs from the
amygdala, olfactory cortex, and limbic basal ganglia. The DM also
projects to frontal cortex in a diffuse manner. Lateral nuclei receiving
nociceptive inputs include the ventral posterolateral nucleus (VPL), the
ventral posterior medial nucleus (VPM), and the pulvinar nucleus (PVN).
VPL receives inputs from the spinothalamic tract and projects in a precise
manner to somatosensory cortex, relaying peripheral nociceptive signals
from the body. The VPM analogously receives inputs from the
trigeminothalamic tract projecting in an anatomically precise manner to
the somatosensory cortex and relaying nociceptive signals originating from
the face. The specificity of inputs and projections associated with lateral
nuclei may underlie why targeted ablation of these nuclei produce sensory
deficits, whereas medial targets with broader inputs and outputs can be
ablated without as many obvious side effects. Anterior targets include the
anterior nucleus of the thalamus (AT). AT receives inputs from the
hippocampus and amygdala and projects to the cingulate cortex.
Intralaminar nuclei receiving peripheral nociceptive inputs include the CL
which is part of the rostral intralaminar nuclei as well as the CM and PF
which are subsets of the caudal group of intralaminar nuclei.

TECHNIQUES
Stereotactic open approach: The general surgical method for stereotactic
ablation of thalamic targets involves awake surgery to simultaneously
record from and identify the nucleus of choice and then ablate it using
thermal energy. The procedure starts by placing the patient’s head in a
rigid stereotactic frame. The frame is then fixed to the operating table in
final position. A pilot CT scan is obtained via portable or intraoperative
CT. This CT image is merged with a previously obtained MRI in order to
determine stereotactic coordinates of the target in relation to the line
defined by connecting the anterior and posterior commissure (AC-PC
coordinates). Coordinates from 6 to 10 mm lateral to the AC-PC line, 7 to
11 mm posterior to the AC-PC midpoint, and from 1 mm below to 2 mm
above the AC-PC line have been used to target DM and CM.49,50 An entry
point is typically chosen near the coronal suture 3 cm from midline. A

5193
curvilinear incision is made and a burr hole drilled and then dura opened in
standard fashion to give access to the brain. Depending on the target and
surgeon preference, microelectrode recordings can be used for localization.
Although there is not always a clear electrographic correlate to localize the
nucleus, in certain cases, neuronal bursting patterns may indicate
deafferentation pain.51 Medial nuclei, in general, provide a large target
with no somatotopic projection pattern. Therefore, electrical recording
may be of little utility; nonetheless, test stimulation for motor and sensory
phenomena can always be conducted as a safety measure prior to
lesioning.46 Using a thermocouple probe, a test lesion is made at a lower
temperature (40° C for 25 seconds), and if the patient shows no adverse
effects, an ablative lesion is made (70° C for 70 seconds).46
Noninvasive radiosurgery and focused ultrasound: Radiosurgery
techniques used for thalamotomy include both Gamma Knife and linear
accelerator methods. FUS is beginning to emerge as an alternate energy
source for creating precise lesions. As imaging technology for lesion
localization becomes more accurate, clinical results of noninvasive
ablative approaches may near those of stereotactic open approaches.52 One
key difference with respect to radiosurgery approaches is the time needed
for lesions to mature following radiation treatment. Young et al.49
describes a case series in which 24 medial thalamic lesions were created
via Gamma Knife using 140 to 180 Gy. The emergence of distinct lesions
via MRI occurred 3 to 6 weeks after the initial procedure and did not fully
mature until 8 to 12 weeks. Ultimately, 9 out of 15 total patients achieved
a greater than 50% pain reduction at 3-month follow-up, which is
comparable to the results of stereotactic ablation. However, if shorter term
pain relief is needed, such as in the context of severe pain and limited life
expectancy, then stereotactic alternatives will need to be considered to
provide prompt palliation to the patient. Moreover, recent results of
noninvasive thermoablation by FUS suggest that it may represent a
tractable alternative. In a case series by Jeanmonod et al.,47 transcranial
MR-guided FUS (tcMRgFUS) was used to perform CL thalamotomies on
12 patients suffering from chronic neuropathic pain. Lesions 3 to 4 mm in
size were made using tcMRgFUS to heat the tissue to 51° C to 64° C as
monitored by MR thermometry. Six patients experienced some degree of

5194
immediate pain relief, whereas a mean pain reduction of 49% was
experienced by nine patients at 3-month follow-up. A randomized sham-
controlled clinical trial is currently underway to assess the efficacy of
ExAblate FUS technology in treatment of refractory chronic trigeminal
neuropathic pain of nonmalignant origin (NCT03309813). The key
technical barrier to improvement in precision and accuracy of both
radiosurgery and FUS techniques is improvement in MR technology for
target localization. Real-time continuous MR imaging and MR
thermometry monitoring dictate both lesion accuracy as well as accuracy
of thermal effects during FUS ablation. As this technology improves, the
noninvasive nature of approach will likely make it a more favorable
alternative to stereotactic thermoablation.

OUTCOMES
Although efficacy of medial thalamotomy has been shown in multiple case
series and case reports, systematic studies of methods, targets, lesion sizes,
and indications have not been conducted. Raslan et al.22 conducted a
systematic review of ablative pain procedure studies including
thalamotomy for malignant pain and found only a handful of reports, all
case series level evidence. The results of the systematic review for
thalamotomy are summarized in Table 105.2, which is adapted from
Raslan et al.22 It is therefore not surprising that there is no consensus as to
a specific nucleus to optimally target for ablation. As mentioned, medial
targets with less somatotopic mapping seem to produce fewer side effects.
In addition, it seems that pain caused by direct tissue damage (nociceptive,
for example from malignant invasion) responds more favorably than
neuropathic pain, although individual reports vary. Sugita et al.55 found
85% had excellent or satisfactory pain relief initially, whereas
Richardson53,54 found mixed results with return of chronic pain occurring
in all patients. The aforementioned noninvasive techniques seem to
produce approximately 50% pain reduction at 3 months postprocedure.52
As with all ablative procedures, the outcome depends in large part on the
circuit pathophysiology prior to intervention and the reaction of the
remaining circuit or network after ablation. As our understanding of pain
physiology advances; as the technology to interrogate the circuitry prior,

5195
during, and after ablation improves; and as our methods of ablation
become more precise, it is possible that the seemingly heterogeneous
outcomes of thalamotomy will become better understood.

TABLE 105.2 Core Outcome Results of Studies of Thalamotomy

for Cancer Pain from 1966 to 2009
Authors and Year No. of Patients Outcome
Whittle and Jenkinson46 2 Adequate pain relief until death

Steiner et al.72 52 8 had excellent pain relief, 18 with moderate

pain relief.
Hitchcock and 16 cancer/53 total Bilateral center-median superior to basal
Teixeira73 thalamotomy

Fairman and Llavallol74 165 70% had no or satisfactory pain relief.

Richardson53 38 total Favorable outcome

Richardson54 24 total Mixed results but return of chronic pain

occurred in all patients
Uematsu et al.75 17 3 excellent, 7 good, 3 no benefit

Sugita et al.55 44/60 85% had excellent or satisfactory pain relief

initially, generally good results in cancer
pain patients.
Leksell et al.76 25 6 pain free, 4 moderate pain relief, effect
noticed after 3 weeks
Shimizu et al.77 8/17 6 had complete pain relief until death (3 died
<1 month postprocedure); 2 had adequate
pain relief, psychological disturbances
common
Fairman78 15/53 80% had bilateral pain relief.
Ramamurthi and 7 All had reasonable pain relief.
Kalyanaraman79
Sano et al.80 10 total Lasting effect in 8 cases

Amano et al.81 14/47 Good pain relief only in thalamic pain or

causalgia
Choi and Umbach82 30/37 91% of all cases had excellent or good results.

Voris and Whisler67 35/58 Pain relief in most patients, few had long
lasting pain relief
Adapted from a systematic review by Raslan AM, Cetas JS, McCartney S, et al. Destructive
procedures for control of cancer pain: the case for cordotomy. J Neurosurg 2011;114:155–170.

Ablative Procedures of the Brainstem

5196
INDICATIONS
Because the anatomical basis of pain transmission was established
throughout the 19th century, surgical procedures for treatment of pain
advanced, leading to cordotomy in 191116 as well as spinothalamic
tractotomy. However, throughout the first half of the 20th century, it
became apparent that existing procedures did not provide long-term relief
of neck, shoulder, and face pain. This led Spiegel and Wycis to pioneer
stereotactic lesioning of the mesencephalon in 1953 and later Hitchcock to
use stereotaxis for lesioning of the pons and trigeminothalamic pathways
in the brainstem.56 Here, we discuss mesencephalic tractotomy (lesioning
of the spinothalamic tract in the midbrain) and ablation of the
trigeminothalamic tract and nucleus caudalis (the caudalmost subdivision
of the spinal trigeminal nucleus). These procedures are indicated in cases
of facial, head, neck, or shoulder pain which are unresponsive to
pharmacologic therapy and more conservative measures. Furthermore, for
pain rostral to C5, cordotomy may be limited, in which case
mesencephalic tractotomy serves as an alternative. Typically, underlying
disorders in which the aforementioned procedures are considered include
geniculate or glossopharyngeal neuralgia, failed trigeminal surgery or
anesthesia dolorosa, posttraumatic neuropathy, postherpetic dysesthesia,
atypical facial pain, and cancer-related pain.1

ANATOMY AND PHYSIOLOGY

The trigeminal sensory nuclei not only receive somatic sensory input in
large part from the trigeminal nerve but also receive input from the facial
nerve (sensation near outer ear), glossopharyngeal nerve (sensation for
middle ear, external auditory meatus, pharynx, posterior third of tongue),
and vagus nerve (sensation for pharynx, outer ear, infratentorial
meninges). The trigeminal nuclear complex extends from the rostral
cervical spinal cord to the midbrain and is made up of the mesencephalic,
chief sensory, and spinal trigeminal nuclei. These nuclei transmit fine
touch, pressure, temperature, and pain sensations from the face to the brain
in an analogous manner to posterior columns and anterolateral systems of
the spinal cord. Namely, the chief sensory nucleus (located dorsolaterally
in the rostral pons) receives synaptic input from large diameter sensory

5197
fibers carrying fine touch and pressure transmission. Cell bodies in the
nucleus give rise to the trigeminal lemniscus in the rostral aspect of the
pons which decussates and travels to the VPM adjacent to the medial
lemniscus in the dorsal brainstem. Fibers carrying crude touch, pain, and
temperature enter the pons and immediately descend via the spinal
trigeminal tract (an analogue of Lissauer’s tract) to synapse on the spinal
trigeminal nucleus in the dorsolateral brainstem starting at the
cervicomedullary junction (the rostral extent of the dorsal horn). The
spinal trigeminal nucleus is subdivided from rostral to caudal into the
nucleus oralis, nucleus interpolaris, and nucleus caudalis (extending
caudally to the C2 segment of spinal cord and substantially overlapping
with substantia gelatinosa containing cervical inputs). The spinal
trigeminal nucleus gives rise to the trigeminothalamic tract which
decussates and ascends to the VPM alongside the spinothalamic tract (in
the dorsal pons at the level of the middle cerebral peduncle). Of note, there
is somatotopic organization of the trigeminothalamic tract and spinal
trigeminal nucleus as described by various authors1,48,57 with an “onion
skin” topology in which the central face is represented rostrally, and the
peripheral face is caudal with V1 to V3 organization assuming a ventral to
dorsal pattern. The mesencephalic trigeminal nucleus and tract together
mediate facial proprioception and are located adjacent to the
periaqueductal gray matter in the dorsal pons. The nucleus houses cell
bodies of proprioceptive neurons, whereas the tract houses axons of these
neurons. Of particular clinical significance is the anatomic relationship of
the nucleus caudalis and spinal trigeminal tract to the dorsal
spinocerebellar tract which is located just lateral on the dorsal surface of
the spinal cord and brainstem as well as the lateral spinothalamic tract,
located ventrally. Extensive lesioning at this level can cause an ipsilateral
ataxia from damage to the spinocerebellar tract or contralateral anesthesia
from spinothalamic tract damage. Similarly, damage to the nucleus
cuneatus which receives dorsal column input and is located in a caudal and
medial direction would cause ipsilateral proprioceptive and fine touch
deficits.1,57 Finally, extensive lesioning of the spinothalamic tract in the
midbrain is known to cause oculomotor deficits as well as ptosis due to
proximity to the oculomotor nucleus and Edinger-Westphal nucleus.58

5198
TECHNIQUES
Mesencephalic tractotomy is performed using stereotactic lesioning via a
radiofrequency probe as previously described.58 Of note, the procedure is
performed under local anesthesia which facilitates intraoperative
stimulation prior to lesioning to ensure that the target has been identified.
Namely, as described by Frank et al.,59 prior to lesioning, an evoked
feeling of thermal sensation should be obtained to ensure the stimulator is
in the spinothalamic tract. Also, while lesioning, sensation and
proprioception should be assessed systematically to ensure the medial
lemniscus is not inadvertently targeted (which could lead to painful
anesthesia following the procedure as observed by Spiegel and Wycis).
The spinothalamic tract can be localized using various imaging protocols
including CT with ventricular contrast or MRI. Integrated data suggest that
most lesions are 5-mm behind the posterior commissure, 5 to 10 mm
lateral, and 5 mm below the AC-PC plane.60 Of note, although the original
procedure was designed to target the lateral spinothalamic (and also the
trigeminothalamic) tracts, evolution of the procedure has included
simultaneous lesioning of the DM of the thalamus in order to disrupt its
prefrontal connections thought to carry the affective “suffering”
component of pain. Similarly, Spiegel et al.61 have advocated a more
medial target to include spinoreticular pathways, also thought to project an
affective component of pain processing to limbic structures.
After satisfactory localization of the spinothalamic tract, a
radiofrequency lesion can be created in stepwise manner. It is also crucial
to assess eye movements and eyelid function throughout this process
because the surrounding oculomotor, abducens, and Edinger-Westphal
nuclei can be damaged causing gaze palsies (see in the following
discussion).
Kanpolat57 has developed a technique for a CT-guided percutaneous
trigeminal tractotomy and nucleotomy. Contrast is injected into the
subarachnoid space via lumbar puncture prior to the procedure, and a CT
is then obtained with careful measurements taken of the depth from skin to
dura. The patient is positioned prone, and local anesthetic is given. The
procedure is done percutaneously using the electrode system developed by
Kanpolat.57 Impedance measurements are initially used to guide electrode

5199
placement. Stimulation is performed with low and high frequencies, and
the patient is monitored for paresthesias of the face indicating the electrode
is in projecting trigeminal nerve axons. Once positioning of the electrode
is acceptable and confirmed by CT, the patient is given additional
anesthesia prior to lesioning, which can be painful. One to three lesions are
made in a stepwise manner starting with a temperature of 50° to 60° C and
then 60° to 80° C for 60 seconds.

OUTCOMES
In a systematic review of ablative procedures for malignant pain control,
Raslan et al.22 reviewed data for both trigeminal tractotomy and
nucleotomy as well as mesencephalotomy (see adapted Table 105.3).
Mesencephalotomy and pontine tractotomy (combined) are rarely
performed (a total of seven studies were cited up until 2011), but effective
pain relief generally achieved in a population of patients with very limited
life expectancy. Trigeminal tractotomy for cancer-related pain, similarly,
was found to have only a small number of studies qualifying for systematic
review with the one noncase series piece of evidence being an open-label
prospective study.62 This study employed standardized outcome measures
of pain and reported sustained pain relief in 80% of subjects at 6 months.

TABLE 105.3 Results of Studies of Mesencephalotomy for Cancer

Pain
Authors and Year No. of Patients Outcome
Bosch83 40 Effective for nociceptive pain

Frank et al.59 202 81% lasting pain relief

Barberá et al.84 6 All cases with pain relief in neck and upper
extremity
Zapletal85 12/16 1 patient with long-term relief

Whisler and Voris86 38 92% patients with pain relief until death

Nashold87 8 All patients with pain relief and with side

effects
Adapted from systematic review by Raslan AM, Cetas JS, McCartney S, et al. Destructive
procedures for control of cancer pain: the case for cordotomy. J Neurosurg 2011;114:155–170.

More recently, in his case series, Kanoplat57 described 81 patients who

underwent 96 CT-guided trigeminal tractotomy and nucleotomy. Sixty-six

5200
(85.7%) patients achieved complete or partial satisfactory pain control,
whereas 15 patients (14.3%) responded poorly to the procedure. The
largest fraction of patients in this series had glossopharyngeal neuralgia.
Of note, at the conclusion of the follow-up period (maximum 216 months),
55 patients (71.4%) achieved sustained pain relief, 13 (16.9%) reported
partial pain control, and 9 (11.7%) reported failure of pain control.
Frank et al.58 describe 14 patients treated with stereotaxic rostral
mesencephalotomy (a total of 19 procedures) for unilateral thoracobrachial
cancer-related pain with frequent neck and/or face involvement. The mean
follow-up time was 4.9 months with 14 procedures leading to good or
excellent pain relief, whereas 4 led to only fair or no pain relief. The
reported complications include two cases with persistent Parinaud
syndrome; one case of bilateral ptosis; and single reports of dysesthesias,
painful anesthesia, and mental changes.58 Kim et al.60 more recently
reported a case of MRI-guided stereotactic mesencephalotomy in which
initial pain control was achieved with a subsequent increase in pain at the
2-month mark. From this and preceding evidence, the authors argue that
mesencephalotomy is rarely indicated for pain other than cancer pain and
thalamic syndrome due to probability of pain recurrence at long-term
follow-up.63

Conclusion
With the development of improved pharmacotherapy, intrathecal delivery
systems, and high-frequency stimulation, ablative procedures for pain have
become less commonly utilized treatment options. Like all functional
procedures, their utility is limited by current knowledge of the underlying
circuitry. Indeed, with the elucidation of nearly every major element of the
pain transmission pathway, there has come a corresponding ablative
procedure. Here, we discussed indications, anatomy, techniques, and
outcomes regarding the DREZ procedure, cordotomy, cingulotomy,
thalamotomy, and tractotomies within the brainstem. Unfortunately, the
complexity, inherent feedback, and nonlinearity of the pain transmission
circuitry has made durable solutions to chronic pain more difficult than
simply ablating component parts of the pain pathway. Systematic study of

5201
ablative procedures is still lacking, but the literature, as we discussed here,
contains many instances of ablative procedures effectively providing relief
to patients with severely intractable pain. As neurosurgical procedures for
pain become less invasive, including techniques that allow one to lesion
without even entering the skull, the need for a thorough understanding and
optimization of ablative approaches is crucial. We anticipate that as
technology and understanding of functional anatomy advances, we will
have the opportunity to readdress ablative approaches and consider more
precise or combination therapies to provide satisfactory pain relief to
patients with no reasonable alternative.

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15. Sindou M. Microsurgical DREZotomy (MDT) for pain, spasticity, and hyperactive bladder: a
20-year experience. Acta Neurochir (Wien) 1995;137:1–5.
16. Spiller WG, Martin E. The treatment of persistent pain of organic origin in the lower part of
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17. Kanpolat Y, Ugur HC, Ayten M, et al. Computed tomography-guided percutaneous
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from cancer: a prospective review of 45 cases. J Palliat Med 2013;16:901–907.
19. White JC, Sweet WH. Pain and the Neurosurgeon: A Forty-Year Experience. Springfield, IL:
C. C. Thomas; 1969.
20. Jones B, Finlay I, Ray A, et al. Is there still a role for open cordotomy in cancer pain
management? J Pain Symptom Manage 2003;25:179–184.
21. Bellini M, Barbieri M. Percutaneous cervical cordotomy in cancer pain. Anaesthesiol
Intensive Ther 2016;48:197–200.
22. Raslan AM, Cetas JS, McCartney S, et al. Destructive procedures for control of cancer pain:
the case for cordotomy. J Neurosurg 2011;114:155–170.
23. Cowie RA, Hitchcock ER. The late results of antero-lateral cordotomy for pain relief. Acta
Neurochir (Wien) 1982;64:39–50.
24. Piscol K. Open spinal surgery for (intractable) pain. In: Penholz H, Brock M, Hamer J, eds.
Brain Hypoxia. Vol 3. Berlin Heidelberg: Springer; 1975:157–169.
25. White JC, Sweet WH, Hawkins R, et al. Anterolateral cordotomy: results, complications and
causes of failure. Brain 1950;73:346–367.
26. Ischia S, Ischia A, Luzzani A, et al. Results up to death in the treatment of persistent cervico-
thoracic (Pancoast) and thoracic malignant pain by unilateral percutaneous cervical
cordotomy. Pain 1985;21:339–355.
27. Ballantine HT Jr, Cassidy WL, Flanagan NB, et al. Stereotaxic anterior cingulotomy for
neuropsychiatric illness and intractable pain. J Neurosurg 1967;26:488–495.
28. Foltz EL, White LE Jr. Pain “relief” by frontal cingulumotomy. J Neurosurg 1962;19:89–100.
29. Scarff JE. Unilateral prefrontal lobotomy for the relief of intractable pain and termination of
narcotic addiction. Surg Gynecol Obstet 1949;89:385–392.
30. Scarff JE. Unilateral prefrontal lobotomy for the relief of intractable pain. J Neurosurg
1950;7:330–336.
31. Meyer A, Beck E, Mclardy T. Prefrontal leucotomy: a neuro-anatomical report. Brain
1947;70:18–49.
32. Sharim J, Pouratian N. Anterior cingulotomy for the treatment of chronic intractable pain: a
systematic review. Pain Physician 2016;19:537–550.
33. Vogt BA, Sikes RW. The Medial Pain System, Cingulate Cortex, and Parallel Processing of
Nociceptive Information. Vol 122. New York: Elsevier; 2013.
34. Devinsky O, Morrell MJ, Vogt BA. Contributions of anterior cingulate cortex to behaviour.
Brain 1995;118(pt 1):279–306.
35. Rolls ET, O’Doherty J, Kringelbach ML, et al. Representations of pleasant and painful touch
in the human orbitofrontal and cingulate cortices. Cereb Cortex 2003;13:308–317.
36. Hutchison WD, Davis KD, Lozano AM, et al. Pain-related neurons in the human cingulate
cortex. Nat Neurosci 1999;2:403–405.
37. Agarwal N, Choi PA, Shin SS, et al. Anterior cingulotomy for intractable pain. Interdiscip
Neurosurg 2016;6:80–83.
38. Steele JD, Christmas D, Eljamel MS, et al. Anterior cingulotomy for major depression:

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39. Cohen RA, Kaplan RF, Moser DJ, et al. Impairments of attention after cingulotomy.
Neurology 1999;53:819–824.2009;16:214–219.
40. Yen CP, Kuan CY, Sheehan J, et al. Impact of bilateral anterior cingulotomy on
neurocognitive function in patients with intractable pain. J Clin Neurosci 2009;16:214–219.
41. Gorecki JP. Thalamotomy for cancer pain, part I. An overview. In: Gildenberg PL, Tasker
RR, eds. Textbook of Stereotactic and Functional Neurosurgery. New York: McGraw-Hill;
1998:1439–1442.
42. Amano K. Thalamotomy for cancer pain, part II. Outcome. In: Gildenberg PL, Tasker RR,
eds. Textbook of Stereotactic and Functional Neurosurgery. New York: McGraw-Hill;
1998:1443–1444.
43. Laitinen LV. Mesencephalotomy and thalamotomy for chronic pain. In: Lunsford LD, ed.
Modern Stereotactic Neurosurgery. Boston, MA: Springer; 1988:269–277.
44. Mark VH, Ervin FR, Yakovlev PI. Correlation of pain relief, sensory loss, and anatomical
lesion sites in pain patients treated with stereotactic thalamotomy. Trans Am Neurol Assoc
1961;86:86–90.
45. Mark VH, Ervin FR. Role of thalamotomy in treatment of chronic severe pain. Postgrad Med
1965;37:563–571.
46. Whittle IR, Jenkinson JL. CT-guided stereotactic antero-medial pulvinotomy and
centromedian-parafascicular thalamotomy for intractable malignant pain. Br J Neurosurg
1995;9:195–200.
47. Jeanmonod D, Werner B, Morel A, et al. Transcranial magnetic resonance imaging-guided
focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain.
Neurosurg Focus 2012;32:E1.
48. Blumenfeld H. Neuroanatomy Through Clinical Cases. Sunderland, MA: Sinauer Associates;
2002.
49. Young RF, Jacques DS, Rand RW, et al. Technique of stereotactic medial thalamotomy with
the Leksell Gamma Knife for treatment of chronic pain. Neurol Res 1995;17:59–65.
50. Niizuma H, Kwak R, Ikeda S, et al. Follow-up results of centromedian thalamotomy for
central pain. Appl Neurophysiol 1982;45:324–325.
51. Jeanmonod D, Magnin M, Morel A. Thalamus and neurogenic pain: physiological, anatomical
and clinical data. Neuroreport 1993;4:475–478.
52. Young RF, Jacques DS, Rand RW, et al. Medial thalamotomy with the Leksell Gamma Knife
for treatment of chronic pain. Acta Neurochir Suppl 1994;62:105–110.
53. Richardson DE. Thalamotomy for intractable pain. Confin Neurol 1967;29:139–145.
54. Richardson DE. Thalamotomy for control of chronic pain. Acta Neurochir (Wien) 1974;(suppl
21):77–88.
55. Sugita K, Mutsuga N, Takaoka Y, et al. Results of stereotaxic thalamotomy for pain. Confin
Neurol 1972;34:265–274.
56. Polin R, Evans R, eds. Neurosurgical Management of Chronic Pain. Published November 5,
2005. Available at:
http://www.medlink.com/article/neurosurgical_management_of_chronic_pain. Accessed
August 31, 2018.
57. Kanoplat Y. Percutaneous stereotactic pain procedures: percutaneous cordotomy,
extralemniscal myelotomy, trigeminal tractotomy-nucleotomy. In: Burchiel K, ed. Surgical
Management of Pain. New York: Thieme; 2002:745–762.
58. Frank F, Tognetti F, Gaist G, et al. Stereotaxic rostral mesencephalotomy in treatment of
malignant faciothoracobrachial pain syndromes. A survey of 14 treated patients. J Neurosurg
1982;56:807–811.

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59. Frank F, Fabrizi AP, Gaist G. Stereotactic mesencephalic tractotomy in the treatment of
chronic cancer pain. Acta Neurochir 1989;99:38–40.
60. Kim DR, Lee SW, Son BC. Stereotactic mesencephalotomy for cancer-related facial pain. J
Korean Neurosurg Soc 2014;56:71–74.
61. Spiegel EA, Kletzkin M, Szekely EG. Pain reactions upon stimulation of the tectum
mesencephali. J Neuropathol Exp Neurol 1954;13:212–220.
62. Watling CJ, Payne R, Allen RR, et al. Commissural myelotomy for intractable cancer pain:
report of two cases. Clin J Pain 1996;12:151–156.
63. Gildenberg PL. Mesencephalotomy for cancer pain. In: Lozano AM, Gildenberg PL, Tasker
RR, eds. Textbook of Stereotactic and Functional Neurosurgery. Vol 1. New York: McGraw-
Hill; 2009:2533–2540.
64. Foltz EL, White LE. The role of rostral cingulumotomy in “pain” relief. Int J Neurol
1968;6:353–373.
65. Faillace LA, Allen RP, McQueen JD, et al. Cognitive deficits from bilateral cingulotomy for
intractable pain in man. Dis Nerv Syst 1971;32:171–175.
66. Hurt RW, Ballantine HT Jr. Stereotactic anterior cingulate lesions for persistent pain: a report
on 68 cases. Clin Neurosurg 1974;21:334–351.
67. Voris H, Whisler W. Results of stereotaxic surgery for intractable pain. Confin Neurol
1975;37:86–96.
68. Pillay PK, Hassenbusch SJ. Bilateral MRI-guided stereotactic cingulotomy for intractable
pain. Stereotact Funct Neurosurg 1992;59:33–38.
69. Wilkinson HA. Bilateral anterior cingulotomy for chronic noncancer pain. Neurosurgery
2000;46:1535–1536.
70. Yen CP, Kung SS, Su YF, et al. Stereotactic bilateral anterior cingulotomy for intractable
pain. J Clin Neurosci 2005;12:886–890.
71. Patel NV, Agarwal N, Mammis A, et al. Frameless stereotactic magnetic resonance imaging-
guided laser interstitial thermal therapy to perform bilateral anterior cingulotomy for
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72. Steiner L, Forster D, Leksell L, et al. Gammathalamotomy in intractable pain. Acta Neurochir
1980;52:173–184.
73. Hitchcock ER, Teixeira MJ. A comparison of results from center-median and basal
thalamotomies for pain. Surg Neurol 1981;15:341–351.
74. Fairman D, Llavallol MA. Thalamic tractotomy for the alleviation of intractable pain in
cancer. Cancer 1973;31:700–707.
75. Uematsu S, Konigsmark B, Walker AE. Thalamotomy for alleviation of intractable pain.
Confin Neurol 1974;36:88–96.
76. Leksell L, Meyerson BA, Forster DM. Radiosurgical thalamotomy for intractable pain. Confin
Neurol 1972;34:264.
77. Shimizu S, Aikawa S, Nishioka S, et al. Stereotaxic thalamotomy for pain relief. Tohoku J
Exp Med 1968;96:219–234.
78. Fairman D. Unilateral thalamic tractotomy for the relief of bilateral pain in malignant tumors.
Confin Neurol 1967;29:146–152.
79. Ramamurthi B, Kalyanaraman S. Stereotactic thalamotomy in pain relief. J R Coll Surg Edinb
1966;12:46–48.
80. Sano K, Yoshioka M, Ogashiwa M, et al. Thalamolaminotomy. A new operation for relief of
intractable pain. Confin Neurol 1966;27:63–66.
81. Amano K, Kitamura K, Sano K, et al. Relief of intractable pain from neurosurgical point of
view with reference to present limits and clinical indications—a review of 100 consecutive

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82. Choi CR, Umbach W. Combined stereotaxic surgery for relief of intractable pain.
Neurochirurgia (Stuttg) 1977;20:84–87.
83. Bosch DA. Stereotactic rostral mesencephalotomy in cancer pain and deafferentation pain. A
series of 40 cases with follow-up results. J Neurosurg 1991;75:747–751.
84. Barberá J, Barcia-Salorio JL, Broseta J. Stereotaxic pontine spinothalamic tractotomy. Surg
Neurol 1979;11:111–114.
85. Zapletal B. Open mesencephalotomy and thalamotomy for intractable pain. Acta Neurochir
(Wien) 1969;(suppl 18):1.
86. Whisler WW, Voris HC. Mesencephalotomy for intractable pain due to malignant disease.
Appl Neurophysiol 1978;41:52–56.
87. Nashold BS Jr. Extensive cephalic and oral pain relieved by midbrain tractotomy. Stereotact
Funct Neurosurg 1972;34:382–388.

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 PART SIX

Provision of Pain Treatment

CHAPTER 106
Interdisciplinary Chronic Pain
Management: Overview and
Lessons from the Public Sector
JENNIFER L. MURPHY and MICHAEL E. SCHATMAN

History of Interdisciplinary Chronic Pain

Management
In the 1940s, John J. Bonica became the first physician to publicly
recognize the complexity of chronic pain syndromes, understanding that
they affect patients not only physically but also across myriad dimensions
of their lives. Chronic pain of nonmalignant origin (i.e., noncancer pain)
has been noted to be the most unpredictable type when compared to acute
and chronic pain due to malignancy, which also makes it the most
challenging to address.1 Bonica found himself frustrated by his inability to
effectively treat those with chronic pain and found that consultation with
his colleagues seemed to benefit all who were involved.2 Because of this,
Bonica developed the first formal multidisciplinary pain management team
at MultiCare Tacoma General Hospital, with members including an
anesthesiologist, orthopedist, neurosurgeon, internist, psychiatrist, and
radiation therapist. However, the model used was multidisciplinary triage
in order to determine which team member would provide treatment and
included only physicians with differing specialties versus professionals

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from entirely different fields.
Concurrently, unbeknownst to Bonica,3 others were simultaneously
developing similar programs in Texas, Oregon, Canada, and Europe.
Although some of these programs were successful, Bonica’s efforts to
change the overall approach to chronic pain management were not so, and
he wrote accordingly, “Despite my persistent drum beating, consisting of
several hundred lectures and the publication of numerous articles in
various parts of the world, the multidisciplinary concept was ignored by
the medical profession for two decades.”4 Fortunately, the integration by
clinical psychologist Wilbert Fordyce of a strong behavioral medicine into
Bonica’s team in the late 1960s was instrumental in the development of the
first multidisciplinary pain evaluation and triage team, which included
disciplines outside of medicine. With the availability of behavioral
approaches to assessment and treatment, the focus of pain clinics shifted
from the eradication of pain to teaching patients how to manage their
symptoms and restore a positive quality of life.5 Behavioral approaches
were soon replaced by cognitive-behavioral approaches, which note only
were less time-consuming and costly but also emphasized the patient as an
active participant in his or her rehabilitation who is able to develop the
coping skills necessary to restore independence.2
Multidisciplinary chronic pain management programs proliferated in the
1970s and 1980s, described as “medicine’s new growth industry.”6 Among
the most active and prestigious of these facilities was that developed by
Bonica at the University of Washington where he was succeeded in
directorship by the neurosurgeon, John Loeser. According to Loeser,7 the
great success of the program was due to the interaction between the
various disciplines of the team members rather than to any specific
intervention that was applied. This encapsulates the magic of
interdisciplinary treatment which is often difficult to explain to outsiders
but easily understood by those who have worked in the milieu. By the
early 1980s, approximately 1,000 multidisciplinary evaluation and
treatment centers were in operation in the United States8 and were
becoming more numerous in other parts of the world as well. However,
these programs were multidisciplinary rather than interdisciplinary.
Contrary to common belief, the first truly interdisciplinary treatment

5208
program was not developed until the early 1980s, when Wilbert Fordyce
and John Loeser opened the facility at the University of Washington that
resembled the modern concept of the interdisciplinary chronic pain
management (ICPM) program (J. Loeser, personal communication,
December 2, 2017).
Although third-party payers were initially enthusiastic regarding these
programs, they soon became less supportive. It is difficult to specifically
determine the point at which the number of interdisciplinary treatment
programs and the availability of this type of pain management began to
decline; however, Schatman9,10 has noted that the number of programs in
the United States accredited by the Commission on Accreditation of
Rehabilitation Facilities (CARF) declined from 210 in 1998 to 84 in 2005;
in 2017, the total number of CARF-accredited pain rehabilitation programs
has dwindled to 67. The availability of ICPM programs in the United
States has flourished only in the Department of Veterans Affairs (VA)
with the Department of Defense following step, a phenomenon which will
be explored in greater depth later in this chapter.

EMPIRICAL SUPPORT FOR INTERDISCIPLINARY

CHRONIC PAIN MANAGEMENT
The evidence to support the clinical efficacy and cost-effectiveness of
ICPM is robust, and the studies are numerous; therefore, it is most efficient
to focus on meta-analyses and systematic reviews that provide the
approach with unequivocal empirical support. These studies will be
reviewed briefly, and several prominent and more recent studies will be
highlighted. Flor and colleagues11 performed the earliest meta-analysis of
ICPM in 1992. The review of 65 studies identified numerous benefits for
participants: reducing medication use, reducing emotional distress,
reducing health care utilization, reducing iatrogenic consequences,
increasing return to work and physical activity levels, closing disability
claims, and an average pain reduction of 20%. Although the figure for pain
reduction may not seem impressive, patients in these programs are
generally told that pain relief is not the goal of treatment and are taught to
focus on functional and emotional benefits. Not surprisingly, ICPM
programs were determined to be superior to unimodal treatments as well as

5209
to no treatment and waiting list controls. The beneficial effects of the
programs appeared to be stable over time. As with most large-scale
reviews, it was recommended that results be interpreted with some caution
due to inconsistencies in methodologies and quality of research designs
and descriptions.
The area of cost-effectiveness for ICPM deserves attention because it is
typically regarded as an intensive and concomitantly expensive option for
chronic pain management; however, a review of the literature does not
support this widely held belief. In 1998, Turk and Okifuji12 performed a
comparative analysis of ICPM programs in order to assess their cost-
effectiveness as compared to surgery, chronic opioid therapy, and
implantable devices. Most striking was the finding that ICPM programs
were up to 21 times more cost-effective than alternative treatments for
chronic pain such as surgery.12 Okifuji and colleagues13 performed a
review of the literature on various treatment approaches to chronic pain,
analyzing the cost-effectiveness of ICPM in comparison to surgery or
conventional medical treatment. ICPM compared favorably to other
treatments in terms of pain reduction, management of opioid analgesics,
restoration of function as measured by activity levels and return to work,
health care utilization, and closure of disability claims. Additionally, the
authors dispelled the myth of ICPM representing an expensive approach to
pain management, calculating that its use in lieu of the other typical
approaches could result in a cost savings of $5 billion per year in the
United States. Turk14 obtained similar findings in a 2002 review, noting
not only that ICPM is comparable to oral medications, surgery, spinal cord
stimulation (SCS), and intrathecal drug delivery in terms of pain relief but
also that interdisciplinary treatment can provide considerable savings in
costs for medications and additional health care utilization. Turk’s14 data
on cost-effectiveness are dramatic, as he determined that interdisciplinary
care is 6.29 times more cost-effective than surgery, 15 times more so than
conventional care, and 25 times more cost-effective than SCS. This opens
up the question regarding why insurance would reimburse procedures such
as SCS but deny any coverage for ICPM programs when the evidence
suggests that this is misguided.
Turk and Swanson15 performed an “analysis and evidence-based

5210
synthesis” of the efficacy and cost-effectiveness of medications, surgery,
SCS, intrathecal drug delivery systems, and ICPM in the treatment of
chronic pain. The authors found that all of these approaches resulted in
roughly the same amount of pain relief, with only ICPM determined to be
essentially free of iatrogenic complications and adverse events as well as
being numerous times more cost-effective than the other treatments
considered in achieving therapeutic goals. Perhaps the most compelling
empirical support for ICPM is provided by the 2001 and 2002 systematic16
and Cochrane17 reviews by Guzmán and colleagues and the 2003
Cochrane review by Schonstein et al.,18 as these studies involved careful
analyses of trial quality. In each of these reviews, the authors determined
that ICPM improves pain and function, which was not determined to be
the case for less intensive treatments.
In an ICPM context and beyond, increasing functioning and optimizing
quality of life often requires the reevaluation of pharmaceuticals. With a
recent emphasis on reducing the use of analgesics that are not always
helpful and potentially harmful, including opioids, it is worthwhile to
include several studies demonstrating the role of ICPM programs in this
effort. A 2013 study by Murphy et al.19 examined the outcomes of more
than 700 participants who completed the inpatient ICPM program at the
VA in Tampa, Florida. Since the program’s advent in 1988, veterans who
enter the program taking opioids are tapered off during the course of their
3-week participation. The study compared how those who were on opioid
medications at program admission fared against those who were not on
opioids.19 There were no significant differences between groups at
admission and all participants improved, but those on opioid analgesics at
program initiation benefitted even more on several domains including
catastrophizing and activities of daily living. A study and 6-month follow-
up conducted by the ICPM program at Mayo Clinic in Minnesota
examined treatment outcomes following opioid analgesic cessation20,21
and found that although patients on opioid analgesics at admission
reported higher levels of pain and depression relative to those not taking
opioids, there were no differences in outcomes at discharge or 6-month
follow-up. Clearly, further research on the effects of opioid tapering on
ICPM outcomes is warranted because the Tampa and Mayo studies

5211
suggest a significant and sustained improvement in pain severity and
functioning following interdisciplinary treatment regardless of previous
opioid status.
Evaluating medications not only is important to patient long-term well-
being but also has financial implications. A novel economic analysis was
conducted in 2015 by Mayo Clinic’s Florida ICPM program in
collaboration with Florida Blue, the state branch of Blue Cross Blue
Shield.22 Sletten et al.22 collaboratively examined the economic impact of
participation in an ICPM on health care utilization and expenditures.
Results indicated decreases in overall medical costs for up to 18 months
including the use of specialty care, tests, and procedures. Of note, unlike
many other cost-effectiveness studies that focus on low back pain, this
ICPM sample included a broad range of chronic pain conditions with an
average pain duration of 8 years. The involvement of a third-party payer in
this analysis represents an important model for future studies because this
may be the most convincing way to garner the support of insurance
companies. This is consistent with Schatman’s work on the demise of
interdisciplinary pain management in the United States, in which he
posited that insurers’ exclusive focus on cost-containment and profitability
trumps pain patient well-being.10 In the future, it would be ideal for ICPM
programs to partner together and enlist the collaboration of multiple health
care plans and payer types to once again demonstrate the economic benefit
of interdisciplinary care.
Given these data, the process by which third-party payers determine
what is worthy of a cost investment can be puzzling. Procedures such as
back surgery, which is costly and risky and yields very mixed empirical
outcomes, are typically covered, yet payers are unlikely to reimburse
evidence-based and lower risk ICPM programs. This in part speaks to the
antiquated yet ongoing biomedical approach that much of the public,
providers, and payers apply to chronic pain treatment. Although it is
clearly a complex biopsychosocial experience that persists across time,
chronic pain continues to be approached in the same manner as acute pain.
This error is a significant reason why individuals and systems seek and
support medical solutions that “cure” pain rather than understanding that
pain can be best minimized and quality of life improved with a whole-

5212
person, comprehensive, self-management approach.

THEORETICAL BASIS OF THE INTERDISCIPLINARY

APPROACH
Before proceeding, it is important to clarify the distinction between
multidisciplinary and interdisciplinary. Although the terms are often used
interchangeably, they are not synonymous. Multidisciplinary treatment
suggests that there are providers from multiple disciplines treating a
patient in parallel. Communication may exist, but is not required, and
varies widely. Coordination of care and treatment planning is atypical and
is unfortunately often fragmented. This is a common approach in primary
and secondary care, in which specialists are consulted as needed and work
in silos. On the other hand, interdisciplinary care is best reflected in a
cohesive team composed of experts from various disciplines who share a
philosophy of care and communicate routinely regarding patient treatment.
They are ideally colocated, although if not, may use technology for
information sharing (e.g., phone calls, e-mails, electronic medical records)
as well as holding scheduled and unscheduled in-person meetings. The
importance of regular communication among team members cannot be
overstated, and consistency in the philosophy of patient care is critical for
program success.
All ICPM is based on the biopsychosocial approach that emphasizes the
complex and dynamic interaction between physiologic, psychological, and
social factors. These variables and how patients respond to them can
exacerbate or ameliorate the patient’s pain experience. For Bonica, the
addition Fordyce contributed to the evolution of the approach by
considering the emotional and behavioral sequelae of chronic pain as well
as nociceptive experience was invaluable. Chronic pain is a disease of the
person, and the person is often obscured by using the traditional
biomedical approach without the integration of other critically relevant
factors.23 Therefore, to effectively treat chronic pain, the motivational-
affective and cognitive-evaluative contributions must be weighed in
addition to the nociceptive. ICPM recognizes the bidirectionality of pain
and psychosocial factors, considering that emotions and maladaptive
behavioral patterns can perpetuate as well as result from persistent

5213
physical discomfort. Regardless of the etiology of pain and even its
comorbidities, patients who have functional impairments can improve on
multiple dimensions if they are provided with appropriate guidance and are
motivated by the staff to exert maximal effort. The goal is for participants
to achieve management of their pain, with an emphasis on increasing self-
efficacy and restoring independence and overall quality of life.

COMPOSITION OF THE INTERDISCIPLINARY TEAM

AND ROLES OF MEMBERS
ICPM is based on the premise that no individual or discipline can “cure”
the patient of all of the ills associated with his or her pain condition.
Although specialization serves to enhance expertise, specialization without
diversification results in limitations to what health care can offer patients
whose conditions are as complex as chronic pain. This, perhaps, was the
greatest wisdom that Bonica contributed to the pain treatment community.
Although the specific construction of ICPM programs vary depending on
factors such as available resources, the typical treatment provided includes
three common elements: (1) medication management, (2) graded physical
exercise, and (3) cognitive and behavioral techniques for pain and stress
management.13 The CARF standards24 identify only two defined
disciplines as essential for ICPM rehabilitation programs: the pain team
physician and pain team psychologist; additional health care professionals
are based on the needs of the persons served. The roles of ICPM team
members that are generally identified as constituting the core as well as
other members that expand and enrich services provided are reviewed in
the following discussion.
Core Team Members
• Physician/medical director: The ICPM program medical director
provides medical leadership and accepts responsibility for the
physical well-being of the patients treated. Although it is important
that the physician possesses expertise in the rehabilitation of pain
disorders, a survey of programs yields wide variance in the training
experience and practice specialties of their medical directors. These
specialties range from physical medicine and rehabilitation to
psychiatry, rheumatology to internal medicine. Of note, the CARF

5214
 standards require that a medical director be a physician who is
certified in their recognized board, has met established
interdisciplinary training requirements, and is involved in the field of
pain and in the ICPM program.24
The precise duties of the medical director vary depending on his or
her engagement in patient care versus nurse practitioners or
physicians’ assistants, which is discussed in the following text. If
involved in a more hands-on role, the physician may take a medical
history, evaluate the patient for purposes of providing or confirming a
diagnosis, analyze test results, manage medications, and in some cases
provide interventions such as trigger point injections. If nurse
practitioners or physicians’ assistants provide much of the direct
clinical contact, the medical director may be called on to see patients
who are most complex or may value from the input of a physician.
The medical director also may represent the program to hospital or
academic leadership. In general, the physician who is seen as warmer
and less directive is likely to foster greater team cohesiveness.25
Similarly, Spoonhour and Schatman26 have suggested that selflessness
is ideal because the most effective medical directors are those who are
willing to allow the team member with certain expertise to function in
a manner maximizing the benefit of that expertise.
• Advanced practice nurses and physicians’ assistants: As mentioned,
the day-to-day duties involved in an ICPM may be carried out by a
nurse practitioner or physician’s assistant. This is done typically to
conserve fiscal resources, although nurse practitioners and physicians’
assistants often have high levels of pain expertise and need limited
input from a physician. They perform duties such as evaluating
individuals for program appropriateness, completing histories and
physicals, managing medication regimens, evaluating patients during
crises, participating in team meetings, and offering input on various
impacts of biomedical information regarding the treatment plan. They
may communicate with the medical director or other physicians often
or seldom, depending on the structure and needs of the specific
program.
• Psychologist: Pain psychologists on interdisciplinary treatment teams

5215
are primarily responsible for the psychosocial aspects and status of
patients’ care. As patients’ pain becomes more chronic, their
development of maladaptive emotional and behavioral patterns
increases, necessitating expert psychological care if they are to
become more functional in their lifestyles. In addition to a medical
director, CARF requires a pain psychologist on the team whose
qualifications include licensure, completion of established
interdisciplinary training requirements, and routine involvement in the
ICPM program.24 Although CARF does not specify the discipline of
the pain program director, this is often fulfilled by the psychologist.
The duties of psychologists in ICPM are vast. Initially, they assist
in determining whether a patient is appropriate for program
participation by evaluating pain-related functional status and
psychological stability. Often, they communicate information
regarding program benefits and expectations. During the program, the
pain psychologist will work with patients on both an individual and
group basis, with an emphasis on identifying more adaptive ways to
respond to pain, acquiring problem-solving and stress management
techniques, decreasing catastrophization, and enhancing self-efficacy.
Through these approaches, reductions in depression and anxiety along
with more adaptive behavioral responses to pain are typically
evidenced.
Although not always the case, psychologists also may serve as the
biofeedback therapist on the ICPM team to facilitate reducing
patients’ psychophysiologic reactivity to stress. Effective use of
relaxation techniques (e.g., progressive muscle relaxation, imagery,
diaphragmatic breathing) are a cornerstone of pain management and
help shift a patient toward internal locus of control27 as well as reduce
tension and pain. In some cases, the biofeedback therapist works in
tandem with the physical therapist, using biofeedback technology to
help patients improve patterns of muscle activation during physical
activities. The ICPM psychologist will also often work with a
patient’s family during the course of a program because the family
may unwittingly be reinforcing the “patient role,” thereby enabling
the patient. Finally, as psychologists are trained as scientist

5216
 practitioners, they are likely to coordinate outcomes information and
performance improvement projects for the ICPM team.
• Nurse: Nurses on ICPM treatment teams often assume diverse
responsibilities and are accordingly invaluable. Because of their
medical backgrounds, they can potentially serve in a variety of roles.
They support other medical staff and often provide education to
patients and their families. In a role delineation study, Pellino and
colleagues28 determined that assessing, evaluating, and monitoring
pain were nurses’ most common activities. Nurses are also the
multidisciplinary team members that spend the greatest amount of
time with patients.29 Additionally, as many nurses are trained and
experienced in case management, a nurse is often the team member
responsible for the day-to-day management of the program.
• Physical therapist: Movement-based therapies are an essential element
of physical activation that is key for effective pain rehabilitation. The
physical therapist on a pain treatment team is responsible for
assessing patients’ levels of functioning and then designing and
monitoring programs of graded therapeutic exercise that will safely
increase these levels. Areas of focus may include increasing flexibility
and range of motion, restoring appropriate posture and body
mechanics, ambulation and gait training, development of core and
limb strength and stability, and decreasing pain-related fear of
movement. Treatment is typically provided on both an individual and
group basis. Modalities such as ultrasound and massage are generally
avoided, as the focus of ICPM is on teaching patients independent
active management of their pain. Stretching and strengthening are
emphasized because these exercises have been empirically supported
through systematic reviews as being among the most effective
treatments for a number of types of chronic pain.30–35 It is critical that
the ICPM physical therapist has received specialized training in
chronic pain management emphasizing a behavioral approach, which
is not the norm; however, for those who value working on a team and
the reward of success with patients with longer standing issues, it can
be an excellent fit.
• Case manager/coordinator: This is a role versus a discipline and can

5217
 be performed by those in various areas but is most commonly fulfilled
by a nurse. Duties are critical for smooth maintenance of the program
and may include triaging referred patients; confirming insurance
sponsorship; development of policies and procedures; quality
assurance; collection and maintenance of patient data; and
correspondence with referral sources, employers, attorneys, health
insurance providers, and other health care professionals treating a
patient.
Other Team Members
• Vocational counselor: The vocational counselor on the treatment team
is responsible for evaluating the capacity, goals, and needs of patients
in the area of return to work, school, or other meaningful activity. A
common aspect of this interaction is helping the patient understand
the benefits of returning to the work force because participating in
gainful employment is considered a primary goal of many ICPM
programs, particularly those that emphasize a functional restoration
approach.36 Vocational counselors may serve as case managers who
contact employers, obtain and analyze job descriptions, and facilitate
return to previous employment. They may also provide testing and
counseling in order to prepare patients for vocational retraining.
Perhaps even more than other team members, it is important for
vocational counselors to understand issues such as primary and
secondary gain as well as the role of psychological factors in
perpetuating perceived disability.
• Occupational therapist: Areas that are considered primarily within the
domain of occupational therapists include ergonomic training, upper
extremity activities of daily living, work activities, leisure activities,
and any other activities that are meaningful and purposeful to the
individual patient. Some occupational therapists perform work-site
analyses, visiting the work place to which the patient intends to return,
observing the specific job-related tasks that he or she will need to
perform, and then developing a work simulation component of the
ICPM program. If a patient has a specific job to which he or she
intends to return, a workplace analysis may be conducted by an
occupational therapist and vocational counselor in order to assess the

5218
 physical and emotional safety of returning to that position.
• Aquatic therapist: When available, the use of supervised exercises in a
heated therapeutic aquatic environment can be a helpful element of
physical rehabilitation and one of those most enjoyed by the patients.
It can be conducted by those in various disciplines but is most
commonly a physical therapist or kinesiotherapist who is interested
and has additional competency in the area. Water-based treatments are
complementary to land-based exercises and have various therapeutic
benefits that are especially helpful for those with chronic pain, such as
buoyancy that reduces the effects of gravity and hydrostatic pressure
that offers stability and support.
• Recreational therapist: Those programs fortunate enough to have the
influence of a recreational therapist reap various patient benefits. Due
to the social isolation that many with chronic pain experience,
recreational therapy typically offers an opportunity to be around
others and practice potentially rusty social skills. Recreational
therapists also evaluate pleasurable activities in which patients wish to
engage (either through initiation or rekindling) and determine how to
help individuals move toward their goals. They often offer options
such as crafts and art work as a means to stimulate creativity, improve
focus, and distract from pain.
• Clinical pain pharmacist: Particularly with the emphasis on
analgesics, the presence of a pain pharmacist can be very helpful in
providing support to medical and other staff as well as to patients
regarding medications. Within the context of ICPM programs, pain
pharmacists typically advise on medication choices, provide
educational classes, and meet with patients as needed to answer in-
depth questions about pharmaceuticals, including addressing issues
regarding polypharmacy, adverse events, and side effect profiles.
• Social worker: Social workers may play a variety of roles in ICPM
programs. They can function in a case manager and coordinator role,
tracking patient participation and addressing issues that arise. If
participation in the program involves travel, social workers often play
an important role in making sure that transportation is arranged and
patients are able to access what is needed at the facility. They also

5219
 provide more traditional guidance on introducing various
administrative forms and can teach classes on how to access
opportunities in the community. Those who are licensed clinical
social workers may have more direct contact to address clinical needs.
In addition to those specialties listed here, many ICPM programs
include other professionals, including a dietician who reviews the
important role of nutrition and weight in pain management, a chaplain who
addresses spiritual needs, a yoga or tai chi instructor who provides guided
direction on these active and beneficial treatments, as well as options such
as an art therapist, music teacher, and other disciplines that encourage the
development of activities that are enjoyable and assist with fostering
positive self-esteem and sense of purpose.

The Process of Interdisciplinary Chronic Pain

Management
Despite the long history and strong empirical support for ICPM, this form
of treatment is often seen as a “last resort” by referral sources, many of
whom have a limited understanding of the complexities of and best
treatments for chronic pain. This is a reflection of a biomedically based
health care system and society that tends to seek passive/receptive
interventions for the management of pain rather than approaching it as a
chronic condition that requires active self-care by the patient as a
foundation for the potential success of other treatment options. ICPM
programs are viewed as tertiary, which too often subsumes that all other
treatments have “failed”; however, it is a treatment best correlated with
complexity and pain-related functional impairment and should be
considered as soon as possible when these conditions are met. If
individuals had access to ICPM programs earlier in their pain journeys, it
is likely that our system could be spared billions of dollars because the
chronification and negative impacts for many would be minimized.
Referrals may come from a wide variety of sources, including other
physicians and health care providers, attorneys, employers, and insurance
carriers. Some ICPM programs are a part of a broader pain management
system, in which case triage may be necessary. Due to economic realities,

5220
insurance coverage is generally confirmed prior to proceeding. Once this is
accomplished, medical records are requested and reviewed to ascertain the
patient’s appropriateness for evaluation. In systems such as the VA,
referrals for evaluation can be made more easily because third-party payer
obstacles are removed and shared medical records facilitate screening
evaluation processes.
The initial evaluation of a candidate for ICPM may occur in a variety of
ways, but the goal is to determine if the individual is appropriate for the
treatment, provide education on the treatment approach, and determine
collaboratively a plan of care. Typically, providers from more than one
discipline are involved in this process so that information regarding all
relevant biopsychosocial factors can be assessed. For example, a medical
professional gathers information regarding medication use and
comorbidities as well as physical fitness and ability, whereas a mental
health professional ascertains details regarding pain-related functional
impacts and emotional and social factors and shares the program’s
philosophy, expectations, and potential benefits from participation.
Physical therapists or others may also be involved in this evaluation in
order to obtain objective measurement of functional capacities. At times,
the patient is deemed to be not currently ready for ICPM due to various
factors including psychiatric or medical instability (e.g., active suicidal
ideation and intention, unmanaged psychosis, cardiac issues). If the ICPM
team believes that these factors can be addressed, delaying admission until
the patient has received appropriate treatment may be in the best interest of
the patient and the program. If the option for reconsideration is not viable,
the program should provide treatment recommendations to the patient and
the referral source.
ICPM programs tend to be intensive, often requiring patients to
participate from 20 to 40 hours per week. Although patients may find the
prospect of such a commitment daunting, they will not be asked to perform
physical tasks that are beyond their functional capacities. Distinguishing
between “hurt” and “harm” and assuring patients that the treatment team
considers their physical and emotional safety to be of the greatest
importance helps build therapeutic trust, thereby enhancing adherence.37
The specific “mix of services” that patients receive between and within

5221
programs will vary. Typically, patients spend significant time engaging in
physical activities that will increase their flexibility, strength, and
functional capacities. Patients whose emotional status and behavioral
responses to their pain are less unhelpful will likely require less time with
the psychologist than will those patients who are struggling
psychosocially. Similarly, patients demonstrating limited
psychophysiologic reactivity to stress will require less intensive
biofeedback training, and those whose vocational issues are more
straightforward will require less concentrated vocational counseling
services. The frequency with which a patient sees the physician and/or
nurse practitioner or physicians’ assistant on an individual basis will vary
depending on the specific program. Frequent individual physician
appointments are generally discouraged because the goal of ICPM is
typically reduction of medical services in lieu of enhanced independent
self-management of pain.
The patient-centered nature of ICPM requires regular team conferences
in which the entire treatment team meets to discuss patient progress, which
includes any issues that are potentially limiting gains and therapeutic
goals. This may happen with the patient, without the patient, or both.
Regardless, feedback to patients should be immediate, consistent, and
coherent. In situations in which patients’ adherence is considered good and
they are making progress, team conference provides a forum in which they
are able to receive much-needed positive reinforcement regarding their
attitude and effort. Patients with chronic pain are often unjustifiably
blamed for the failures of the primary and secondary care systems to help
them recover, making appropriate positive reinforcement even more
important. Conversely, in cases in which adherence and progress are
considered by the team to be inadequate, the conference provides an
opportunity for the treatment team to develop an approach for patient
feedback and/or to present a united front in addressing the relevant issues
and work with patients to remedy any problematic aspects of their
programs. Because the literature confirms that individuals with personality
disorders are prevalent in ICPM programs,38,39 it is not unusual to
encounter attempts to “split” treatment team members. Because of this, it
is particularly important for the program team to develop a coherent plan

5222
together and enforce it consistently so that patients receive a unified
message throughout their participation. Unfortunately, although ICPM
programs work to facilitate success for all patients, some circumstances
necessitate early discharge. Stanos40 has recently suggested that such
premature discharge can potentially encourage enhanced compliance or
efforts among other patients in the group.
Once a patient has completed an ICPM program, he or she can be
neither forgotten nor abandoned. Although programs are typically close-
ended, some form of follow-up to determine implementation of what has
been learned in the program is important. Additionally, if the program is
involved in outcomes research, follow-up provides a source for collection
of more data. For the sake of cost-efficiency, selected measures of
patients’ emotional and behavioral responses to their pain that are
administered can be sent to them to determine longer term outcomes and
identify any clinical needs. Positive outcomes data should serve as a
powerful tool for demonstrating the program’s effectiveness to patients
and providers which can assist with marketing. Potential referring
physicians may be uninformed regarding the wide range of benefits of
interdisciplinary treatment for their patients, and well-organized data may
help them understand how a program can make their own lives easier as
well as helping their more challenging patients. Additionally, although
some health insurance programs may argue against the efficacy of ICPM,
data that invalidates their arguments will ideally help convince them of the
legitimacy of this treatment approach.

Interdisciplinary Chronic Pain Management in

Veterans Healthcare Administration: Overview of a
Model System
Although ICPM programs have greatly diminished in the United States in
the last 20 years, there is one place where they have flourished: the VA
health care system.41 The VA undertook specific efforts to highlight the
need for improved pain care in 1998. At that time, leaders in the VA
acknowledged that pain was an underrecognized and undertreated issue
that impacted veterans across the continuum of care. This led to a series of

5223
successful initiatives and collaborations that increased the measurement,
tracking, treatment, and overall quality of services available to veterans
with pain. One of the most important was a 2003 pain management policy,
the first of its kind and an important step toward establishing pain as a high
priority for the Veterans Healthcare Administration (VHA).42 In 2004,
pain management was established as a separate organizational entity
within VA Central Office under the direction of clinical psychologist,
Robert D. Kerns. Among many identified areas of focus was an emphasis
on multidisciplinary and interdisciplinary pain care, the least common
models previously found in the community.
In 2009, a revised VHA pain directive was established which introduced
a stepped care approach to pain management as the standard for the VA.43
It not only reasserted VHA’s commitment to an approach that is informed
by a biopsychosocial model of pain and an interdisciplinary,
multidimensional, and multimodal approach to pain management but also
asserted that improved quality of life, rather than pain relief per se, is the
accepted standard outcome measure of effectiveness. In addition to many
other recommendations such as establishing facility multidisciplinary pain
committees and specific research efforts, the stepped care model
delineated the primary level Patient Aligned Care Team (PACT) and
reinforced secondary level specialty pain care (e.g., pain medicine,
behavioral health). The tertiary level was defined as interdisciplinary care
for the most complex, treatment refractory, and at-risk patients. Along
with the availability of advanced pain diagnostics, VHA made a
commitment to developing at least one interdisciplinary pain rehabilitation
program in each Veterans Integrated Service Network (VISN) by the end
of September 2014. These programs were to be accredited by CARF,
ensuring the highest level of quality for care.
At the time the directive was published,43 there were only two CARF-
accredited programs in the VA system, located in Tampa, Florida, and San
Juan, Puerto Rico, both in VISN 8; therefore, developing and
implementing programs for the other 20 VISNs was an ambitious mandate.
Five years were allotted to accomplish the goal, with no particular pathway
defined for how each different region or facility would meet it.
Furthermore, no resources were provided by VA Central Office, and the

5224
details and timeline of implementation were left to the VISNs. The VA
pain team training program was established under the leadership of clinical
psychologist, Michael Clark at the James A. Haley Veterans’ Hospital in
Tampa, Florida, site of the longest standing CARF-accredited pain
rehabilitation program in the VA. Over the next 5 years, the program
directly assisted facilities with training visits, providing models and
advisement in their fulfillment of the directive as well as ongoing
consultation as needed. Tampa trained over 30 VA teams in the
philosophical and practical foundations of an interdisciplinary pain
rehabilitation program, many of whom went on to implement their own
versions at local facilities.
In 2017, the VA’s 20 programs represent almost a third of the 67
CARF-accredited pain programs that are available in the United States,
even though veterans served by the VA represent only a fraction of the
nation’s population. Although the overall presence of programs has
steadily decreased in the United States, the VA has maintained an upward
trend and taken steps to coordinate these centers across the country. The
first author of this chapter (JLM), the VA’s liaison for the development
and maintenance of CARF programs, formed a national CARF Pain
Programs Leadership Committee in late 2015 which serves as a
community of practice and forum for collaboration across CARF sites.
Through regularly scheduled calls, members share questions and updates
and consult with each other in order to maintain the CARF standards. As
an example of collaboration across sites, a group of VA programs
established mutually agreeable core outcome measures to foster a means
for comparison of program outcomes. Although not required, this effort
serves as a model for the level of coordination that may one day become
standard across the system as a means for continual program improvement.
The current state of affairs begs the question, “Why is the VA
committed to ICPM programs more than the private sector?” There are
several explanations which have been reviewed by LaChappelle et al.42
First, the VHA emphasizes those treatment options such as ICPM, which
have the greatest evidence base. This is supported in the mission statement
of the VA as well as in the policies for interventions and pharmaceuticals.
Undoubtedly, another factor is the cost–benefit analysis of lifelong patient

5225
care that takes into account and often prioritizes long-term outcomes over
short-term outcomes. Outside the VA, third-party payer health insurance
plans will often fund and reimburse care that may be less expensive in the
short term but may be more expensive in the long term, since changes in
insurance coverage occur routinely. However, a system that treats patients
for the span of their lives is more likely to value an initial higher financial
cost of multidisciplinary treatment. This investment in the interdisciplinary
approach achieves greater health and well-being in the long term rather a
than lower cost financial investment in the short term, with poorer health
outcomes in the long term.44,45 Although a number of factors contribute to
frequently switching health insurance carriers in the private sector, the
behavior results in a disincentive for insurers’ coverage of ICPM
programs. Despite the literature supporting their cost-efficiency, they are
considered a formidable expense in the short term, and accordingly,
insurance payers are more likely to cover inferior (and often more
dangerous) but less expensive treatment options. Sadly, if insurance
companies would recognize that the investment in ICPM care is well
worth the cost, these programs would flourish outside of the VA system
and all would benefit as demonstrated by the 2015 Mayo Clinic study.22
There are numerous lessons to be learned from the growth of ICPM
programs in the VA. First, although many in the private sector perceive the
VA system to be flushed with endless resources, the limitations of space
and personnel are familiar barriers across the system. Because of this,
programs have taken a variety of forms, tailored and built to fit the unique
picture of each particular facility. For instance, a program that is 2 to 3
days per week may require 25% of a full-time physical therapist who also
works in other settings. Others in less routinely incorporated specialties
such as a chaplain, dietician, pharmacist, or addictions counselor may be
able to provide a group once during the course of a program, something
that adds greatly to the richness of program content while not taxing
human resources. Although these creative strategies could theoretically be
helpful in convincing insurers to reconsider coverage of ICPM programs,
“carving out” essential aspects of them has been empirically established as
resulting in far less favorable outcomes.46,47
In addition, VA’s model of setting an administrative mandate for one

5226
CARF ICPM program per region was an ambitious goal, yet it has served
several purposes. First, it represented formal recognition by leadership of
the importance of interdisciplinary care. Second, although the number was
insufficient to serve the entire veteran population, the emergence of ICPM
programs throughout the country introduced the treatment approach to
providers and patients who were previously unfamiliar. This has served to
reinforce the need for a biopsychosocial model and increase access to
additional pain care options that are not strictly medical or pharmacologic.
Because insurance companies appear unlikely to return to coverage of
ICPM programs, a legislative mandate supporting ICPM programs is
necessary to effect a restoration of reimbursement for this effective mode
of chronic pain treatment. As in the VA, it took a national pain directive
recognizing a public health need to spur the development of this valued
treatment option and a similar call from on high is needed in the private
sector.

Future Considerations for Interdisciplinary Chronic

Pain Management
Chronic pain is and has been underrecognized and undertreated as a health
care need. Although the biopsychosocial model is recognized as the gold
standard for pain care, in reality, the biomedical model continues to reign
supreme. This means that despite the overall clinical efficacy and cost-
effectiveness of ICPM programs, the number in the United States has
decreased precipitously since 1999 (A. Whitney, personal communication,
July 16, 2007), thereby severely limiting the availability of a treatment
approach that has been the most rigorously validated. The demise of these
programs is a disturbing phenomenon particularly given the cost of chronic
pain and the drastic increase in opioid use disorder and opioid-related
overdose deaths. As Chapman states, “Concurrent with the decline of
intensive programs is the rise of procedural interventions and medication,
which receives a great deal of support from medical technology and
pharmaceutical companies.”48 These unfortunate realities only underscore
the need for an approach to chronic pain that matches its complexities
without defaulting to a unimodal medical attempt to cure something which

5227
requires long-term management.
One potentially positive result of America’s prescription opioid crisis
has been a shift in focus to treatments that are nonpharmacologic. This has
significantly increased the interest of some in options such as pain
psychology, complementary integrative health (e.g., acupuncture, yoga),
and ICPM programs which provide comprehensive care with a decreased
focus on medical modalities and an increased emphasis on self-
management strategies. It is unfortunate that it took the drastic increase in
opioid prescribing and related negative events to propel health care
professionals, systems, and even lawmakers toward considering treatment
options that capture the biopsychosocial approach, but the momentum is
welcome. Additional funding for treatment options as well as research that
considers physiologic as well as other highly relevant factors in the
chronic pain experience may lead to improvement in the availability of
ICPM options. The growth of interdisciplinary pain rehabilitation
programs within the VA demonstrates a cultural transformation within the
largest single health care system in the United States, one that should be
used as a model for how to walk the walk of whole person pain care across
the country.

Conclusion
Seventy years after Bonica introduced the concept of interdisciplinary pain
management, those who work in the field sadly continue to encounter
similar challenges to those that he faced. The lack of acceptance by the
medical community of the interdisciplinary approach that left Bonica
ready “to give up” still challenges those that rightly acknowledge the
necessity of an interdisciplinary treatment model for optimal patient
outcomes. Despite substantial and unequivocal empirical support for its
clinical utility and cost-efficiency, in every setting but the VA, the number
of programs in the United States has dwindled. Patients have been forced
to resort to less effective, more expensive, and often more dangerous
treatment options which tend to focus on body parts as opposed to the
person in need.
Although third-party payers and some in the field suggest that the ICPM

5228
model should be pared down to deintensify the commitment by providers
and patients, the evidence suggests the opposite: Providers, payers, and
patients should instead embrace the intervention which best matches the
treatment needs of those with complex chronic pain. The evidence
indicates that the model is not broken—the system is. As one of the most
pervasive and costliest health care issues, chronic pain and the ICPM
approach deserves the attention and support of legislators, insurance
companies, and the health care industry at large. Those who have the
privilege of working in a true interdisciplinary framework must be the
leaders in this mission: to advocate, to educate, to model, and to celebrate
the patients with whom they have the ability to effect change. The noble
practitioners of the interdisciplinary approach need to become ICPM
“champions” to defend the life of that which science and clinical
experience tells us is the closest thing we have to a “cure” for our patients.

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30. Swenson RS. Therapeutic modalities in the management of nonspecific neck pain. Phys Med
Rehabil Clin N Am 2003;14:605–627.
31. Kay TM, Gross A, Goldsmith C, et al; and the Cervical Overview Group. Exercises for
mechanical neck disorders. Cochrane Database Syst Rev 2005;(3):CD004250.
32. Arnold LM. Biology and therapy of fibromyalgia. New therapies in fibromyalgia. Arthritis

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33. Joines JD. Chronic low back pain: progress in therapy. Curr Pain Headache Rep 2006;10:421–
425.
34. Gross AR, Goldsmith C, Hoving JL, et al; and the Cervical Overview Group. Conservative
management of mechanical neck disorders: a systematic review. J Rheumatol 2007;34:1083–
1102.
35. Taylor NF, Dodd KJ, Shields N, et al. Therapeutic exercise in physiotherapy practice is
beneficial: a summary of systematic reviews 2002–2005. Aust J Physiother 2007;53:7–16.
36. Mayer TG, Gatchel RJ. Functional Restoration for Spinal Disorders: The Sports Medicine
Approach. Philadelphia: Lea & Febiger; 1988.
37. Hatzakis M, Schatman ME. The impact of interventional approaches when used within the
context of multidisciplinary chronic pain management. In: Schatman ME, Campbell A, eds.
Chronic Pain Management: Guidelines for Multidisciplinary Program Development. New
York: Informa Healthcare; 2007:101–115.
38. Schatman ME. The challenge of the characterologically disturbed chronic pain patient. Pain
Pract 2003;13:5–7.
39. Schatman ME. Dramatically disturbed patients in interdisciplinary pain programs. Pract Pain
Manage 2004;4:24–29.
40. Stanos S. Developing an interdisciplinary multidisciplinary chronic pain management
program: nuts and bolts. In: Schatman ME, Campbell A, eds. Chronic Pain Management:
Guidelines for Multidisciplinary Program Development. New York: Informa Healthcare;
2007:151–172.
41. Schatman ME. Interdisciplinary chronic pain management: international perspectives. Pain:
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42. LaChappelle K, Boris-Karpel S, Kerns RD. Pain management in the Veterans Health
Administration. In: Miller TW, ed. Veterans’ Healthcare: Volume IV. Future Directions for
Veterans Healthcare. New York: Praeger Publishers Inc; 2012.
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Directive 2009-053. Oct 28, 2009. Available at:
https://www.va.gov/painmanagement/docs/vha09paindirective.pdf.
44. Boris-Karpel S. Policy and practice issues in pain management. In: Ebert MH, Kerns RD eds.
Behavioral and Psychopharmacologic Pain Management. Cambridge, United Kingdom:
Cambridge University Press; 2007:407–433.
45. Martell BA, O’Connor PG, Kerns RD, et al. Systematic review: opioid treatment for chronic
back pain: prevalence, efficacy, and association with addiction. Ann Intern Med
2007;146:116–127.
46. Gatchel RJ, Noe C, Gajraj N, et al. The negative impact on an interdisciplinary pain
management program of insurance “treatment carve out” practices. J Work Compens
2001;10:50–63.
47. Robbins H, Gatchel RJ, Noe C, et al. A prospective one-year outcome study of
interdisciplinary chronic pain management: compromising its efficacy by managed care
policies. Anesth Analg 2003;97(1):156–162.
48. Chapman SL. Chronic pain rehabilitation: lost in a sea of drugs and procedures? Am Pain Soc
Bull 2000;10(suppl 3):8–9.

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CHAPTER 107
Spine Clinics
JAMES D. KANG, HAI V. LE, and KENNETH C. NWOSU

Back pain is one of the most common chief complaints in the emergency
room and primary care clinic. It is composed of a wide range of symptoms
with varying characteristics. Patients may present with or without
associated neurologic signs or symptoms. Adding to this complexity is the
multiple potential pain generators that exist in the spine, which include
disks, facets, bones, muscles, ligaments, and nerves. For these reasons,
back pain presents a great challenge to health care providers, one where it
is difficult to correctly identify an underlying cause and develop an
efficacious treatment.
Anatomically, the human spine is a structure of tremendous intricacy.
Consider, for example, the primary roles of the spine—support and
flexibility. On one hand, it must be strong enough to maintain an upright
posture. On the other, its elastic properties should permit broad motion
through flexion, extension, lateral bending, and rotation. The spinal
column also has a protective function to surround and cushion the delicate
structures of the spinal cord and nerve roots. It is capable of accomplishing
these tasks through a conglomeration of bones, joints, ligaments, disks,
and neural elements. Spinal anatomy is further complicated by the number
of mobile segments, the proximity of the spinal cord and nerve roots, the
intricate motions of multiple small joints, and the natural changes that
occur with aging.
Knowledge of the intricate biochemistry of the intervertebral disk and
the role of inflammatory mediators in back pain continues to expand.
There is also a significant psychological component that impacts the
behaviors of patients with back pain and their recovery from injury.
Considering the complexity of the spine, it is understandable that
definitively diagnosing the exact source(s) of symptoms is often difficult
and sometimes impossible.1 This task is made even more difficult by the

5232
strong impact of personality in reporting and dealing with pain,
particularly work-related low back pain.2
The spine is continually beset by physical stresses, and once an
individual reaches adulthood, it is in a constant state of degeneration. The
very complexity of the human spine creates the conditions that make it so
difficult to resolve back pain. With so many complex and interacting
structures, pain can arise from individual structures, multiple structures, or
their dynamic interaction. As noted by Jerome Groopman3 in his best-
selling text, How Doctors Think, “given all of these structures, the source
of the chronic . . . back pain is often a mystery. Doctors can be hard-
pressed to identify why a patient is uncomfortable.”
Despite its complexity, back pain is nearly universal in the general
population with a lifetime prevalence of 65% to 80% in the United States
and an annual economic impact that ranges from $84.1 to $624.8 billion.4
Using data from the 2002 National Health Interview Survey, Strine and
Hootman5 reported that the 3-month prevalence of back and/or neck pain
among adults in the United States was 31%. Understandably, these
subjects generally had more comorbid conditions and greater
psychological distress than did subjects without back or neck pain.
Supportively, some studies have indicated that psychosocial factors have
an even more influential contribution than mechanical factors toward back
pain.6 In addition, Fanuele et al.7 using the Short Form Health Survey (SF-
36) general health status questionnaire reported back pain patients were
significantly impaired, even when compared to a variety of other health
conditions. In order to effectively treat such patients, one must understand
the severity of the problems and appreciate that back pain may often be
accompanied by a variety of comorbidities.
The patient with chronic back pain is often passed from practitioner to
practitioner, at times of widely varying expertise, training, and experience,
and each subjecting the patient to his or her own preferred techniques for
palliation. As the patient drifts further into disability, pain, and medication
use, desperation and the cost of single-modality treatments increase in
parallel, whereas the probabilities of overcoming the pain and of
improving function diminish. It is, according to Groopman,3 “as though
each approach to diagnosis and treatment is essentially a ‘franchise’ and

5233
that too many franchises are battling for control.” Such a state of affairs
leads to treatments that are increasingly expensive, unfocused,
unsubstantiated, and ineffective.
Thus is the complexity of chronic back pain and the costly, untenable
nature of many treatments. All point to the need for a different approach to
manage back pain where improvement in value depends on improved
performances and accountability among individuals who have a shared
goal that unites the interests and activities of all stakeholders. The desired
approach is no different now from that developed for general chronic pain
by Dr. Bonica, and aptly described by Loeser et al. in the third edition of
Bonica’s Management of Pain.8 They state that Dr. Bonica
. . . brought clinical psychologists, pharmacists and other non-
physician providers to the conference table with anesthesiologists,
neurologists, physiatrists, neurosurgeons, orthopedic surgeons,
psychiatrists and others. This blend of perspectives kept each
specialist from exercising specialty-specific tunnel vision, and in
conferences a group understanding often emerged that greatly
exceeded the understanding that the record would yield after a series
of serial consultations.
This is an apt description of the multidisciplinary approach to care. Of
course, a multidisciplinary approach alone does not guarantee either
efficiency or effectiveness. In order to provide maximally effective and
efficient treatment, and to limit treatment costs, a spine treatment facility
must include practitioners with the highest levels of training and
experience, who follow treatment guidelines that are scientifically
validated yet flexible enough to address the idiosyncrasies of individual
patient problems. The care needs to be carefully coordinated to avoid
duplication, unnecessary expense, and use of treatments with limited
possibility of success. A number of specific principles should guide the
multidisciplinary spine facility:
1. Specific algorithms for evaluation and treatment
2. Ongoing multidisciplinary case management and case discussion
3. Active process of continuous quality improvement including
outcome measurement, assessment of patient satisfaction, and use of
results to improve treatment algorithms

5234
 4. Professional education of treatment team members
5. Participation in active research programs
In this chapter, we discuss the key elements needed to establish and
maintain an effective multidisciplinary spine facility.

Treatment Components
The three major components that comprise the clinical aspects of a
multidisciplinary spine center are (1) a group of dedicated, highly trained
physicians and allied health providers with expertise in spine care, (2) a set
of treatment algorithms guiding assessment and intervention, and (3)
active and aggressive case management, especially when patients fall
outside of established treatment algorithms. One of the keys of a
successful center is building a multidisciplinary team that understands and
respects the roles and skills of individual team members. In caring for
patients with acute or chronic back pain, we emphasize the importance of
interprofessional communication and teamwork among all care providers
(Fig. 107.1).

FIGURE 107.1 Illustrative diagram demonstrating the intricate relationships between care
providers and the patient at a comprehensive spine center. Close communication among the various
providers and the patient is required to provide the highest level of clinical care.

5235
Treatment Providers
CONSERVATIVE CARE GATEKEEPERS
Of the many individuals who experience back pain, only about 10% ever
undergo spine surgery.9 It is therefore logical that the initial evaluation of
patients presenting to a comprehensive spine center should be conducted
by a “conservative care” physician—one who is specially trained in the
assessment and treatment of spinal disorders. These physicians should be
competent in triaging patients and placing them into appropriate
assessment and treatment algorithms. Complicated cases and those
requiring urgent or emergent intervention can be promptly identified and
referred for appropriate diagnostic workup and intervention. However, the
majority of cases will be best handled using standard treatment algorithms
in which resolution of the back pain is expected with minimal intervention.
Such physicians may include primary care doctors or specialists in
anesthesiology, physical medicine and rehabilitation (PM&R), or
occupational medicine. All of these providers must be able to recognize
the “red flags” of back pain, which warrant further lab or imaging studies
and timely intervention.

PAIN MANAGEMENT
The most ubiquitous and bothersome indication of spine injury is back
pain. Unremitting pain, often fluctuating randomly, can decimate both
emotional stability and physical capability. Physicians now have a diverse
armamentarium of oral, topical, and injectable medications that may
provide immediate, and at times prolonged, relief. The mainstay
nonprescription medications for the treatment of back pain are
acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).
Prescription oral medications include muscle relaxants, opioids,
corticosteroids, and certain antidepressants and antiseizure medications.
The opioid analgesics, even in recently developed time-release
preparations, carry with them both the potential for physical dependence
and addiction in up to 40% of chronic pain patients10 which have been
reported to cost upward of $53 billion to treat.11 Therefore, it is imperative
that only one provider in a multidisciplinary team is prescribing and

5236
managing the medications. A pain treatment agreement should be
implemented early on. Targeted injections are of some value in specific
conditions (see Chapters 99 and 100 for a detailed discussion), but their
use requires sophisticated equipment and advanced training in order to be
used safely and effectively. Physicians with subspecialty training in pain
medicine, often specially trained anesthesiologists or PM&R specialists,
can effectively use injection therapy, but these treatments must be used in
coordination with the other evaluation and treatment efforts, including
physical therapy (PT).

PSYCHOLOGY
Patients suffering with spinal injuries and back pain experience dramatic
emotional and social changes. Up to 80% of patients with persistent back
pain are diagnosable with clinical depression,12 and many will express
anger as the most common emotion they experience.13 Fear and avoidance
of pain often drive patients into unnecessary functional decline. Marriages
and relationships can shatter, and spine injuries often leave economic
devastation in their wake. For these reasons, specifically trained
psychologists often play a pivotal role within the spine center. Numerous
studies have shown that psychosocial factors can complicate recovery
from spine surgery (see Chapter 76 and Block et al.14 for a review). Thus,
one of the major functions played by psychologists is to perform
presurgical psychological screening, providing information to surgeons
about the level of psychosocial risk found in patients who are being
considered for spine surgery. Such a process allows the surgeon to
individualize treatment protocols. In patients who have a high level of
identified psychosocial risk, alternatives to spine surgery can be
considered. Psychologists often see nonsurgical patients as well, helping
them cope with the emotional sequelae of spinal injury and to help them
learn new means of coping with pain and its limitations. Social workers
can also play a pivotal role in counseling these patients while establishing
support network to help them recover.

PHYSICAL THERAPY
Many patients with back pain require little intervention from a physician.

5237
Their problems are related to body mechanics and deconditioning. For this
reason, a conservative approach to the treatment of back pain incorporates
PT as a first-line treatment. Frequently, therapists provide a combination
of strengthening, stretching, palliative modalities (such as heat or electrical
stimulation), and hands-on muscle activation that offer good pain relief.
Fritz et al.15 found that patients with acute spine pain who have high
adherence rates to active PT-based exercise programs achieve excellent
reductions in disability and pain. Symptomatic management with
structured PT may delay or avoid more invasive interventions altogether.
Another benefit of PT is that patients often continue the activities they
learned during therapy well beyond their treatment course. Many
rehabilitation centers provide patients a home exercise program as their
formal treatment period ends. Additionally, getting into the habit of
exercise during PT may encourage patients to continue a more active
lifestyle, improving their general health as well as potentially decreasing
their back pain.

OCCUPATIONAL THERAPY
One of the most challenging and costly aspects of back pain is effectively
managing patients who suffer workplace-related back pain. Patients with
pain that is inadequately treated may function poorly at work, which can
lead to termination of current employment, unemployment, and disability.
Occupational therapists play a central role in conducting structured
functional evaluations to determine the patient’s current level of
performance compared to their job demands. Their primary goal is to help
restore patients to their baseline functional status so they can lead a
productive lifestyle at home and at work. Of note, in many settings,
physical therapists take on part of the role of occupational therapists.
It is important to remember that the response to physical and
occupational therapy may vary among patients, as is the duration of
therapy required before a response is observed. Therefore, therapy is
generally recommended for at least 6 weeks. With regard to conservative
management of back pain, if standard treatment modalities are ineffective,
patients may be encouraged to explore alternative options such as
chiropractic and acupuncture.

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SPINE SURGERY
Spine surgery is the topic of much discussion as many surgeons are
devoted to developing novel implant designs and operative techniques. As
previously noted, only about 10% of patients seeking care for back pain go
on to have surgery. The most important, and arguably the most difficult,
aspect of spine surgery is choosing the appropriate indications for surgery.
Although the outcomes for surgery for radicular leg pain and neurogenic
claudication are more predictable and favorable, surgery for back pain
without any clear underlying etiology is less so. When patients have
exhausted nonoperative treatment options for back pain, the default
unfortunately is to resort to surgery. However, operative intervention is
generally not recommended for pure mechanical back pain, as surgery can
lead to more pain and disability. This dilemma highlights the importance
of having an interdisciplinary spine care team that upholds high standards
and expectations while holding each member accountable for high-quality
patient care. Even when the indications are appropriate to proceed with
surgery, the risks involved, as well as the costs, mandate that surgery is
used sparingly and only when nonoperative options have failed to provide
adequate symptomatic relief.
A spine center of excellence certainly needs a group of well-trained
spine surgeons. Although not frequently addressed in the literature, there
has been some investigation into the relationship of surgeon experience
and complications associated with spine surgery. Wiese et al.16 found that
the complication rate following lumbar microdiscectomy was significantly
less among surgeons with a greater level of experience (2.2% vs. 10.7%).
In results from a multicenter total disk replacement study, it was reported
that among the high-enrolling surgeons and/or centers, the length of
hospital stay, operating time, and complication rates were significantly less
than among low-enrolling sites.17 Results of the studies suggest that
established spine centers that make use of a team of specialists with
varying expertise have an advantage over individual physicians with
respect to complication rates.
Although surgery is sometimes viewed as the “end of the road” in
treatment, this should not be the case. Although surgery is a dramatic
event, it is only one step in a continuum of care. Treatment does not end

5239
with surgery. Most patients who undergo spinal surgery will not have been
engaging in typical activities due to pain. Although the surgery may
address the structural component of their problem, it cannot address the
deconditioning that has occurred. In a spine clinic, there are postoperative
rehabilitation protocols for the various types of surgery performed. In this
day of escalating surgical options and approaches, physical therapists must
gain a clear understanding of each operative intervention and lend their
expertise to developing safe and effective rehabilitation protocols that will
maximize functional recovery after surgery. For example, a therapist not
working closely with spine surgeons may have a difficult time devising the
most appropriate and safe program for a patient who has undergone
surgery using a nontraditional approach such as the trans-sacral approach
to the L5–S1 disk space or extreme lateral interbody fusion for other
lumbar disks. Some new procedures require avoidance of specific motions
early after surgery with guided progression back to full activity.18 Without
an understanding of the goals and functions of new implants, it is unlikely
that a physical therapist working in isolation will be able to design an
optimally safe and effective rehabilitation regimen.
Surgeons at a specialty spine center should be slow to adapt new
technologies and techniques, and the group’s practice should be
standardized and evidence-based. One of the advantages of a spine
specialty center is the enhanced opportunity for surgeons to participate in
clinical trials evaluating new technologies. These centers are often
preferred sites due to the expertise of the surgeons and the ability to have a
large enough patient population to meet enrollment needs. The benefit to
the surgeons is that they can offer patients interventions that would
otherwise be unavailable outside of an investigational setting for many
years to come. Patients have the benefit of participating in clinical trials if
they meet the selection criteria and elect to participate. The
multidisciplinary nature of an established spine center offers the optimal
atmosphere for testing new and emerging technologies for treating spinal
disorders.

CHRONIC PAIN MANAGEMENT PROGRAM

The multifaceted nature of spine injuries points to the importance of

5240
approaching spine treatment in a multidisciplinary fashion. After
treatment, patients must often resume a life where the very assumptions
and boundaries have been greatly distorted, all too often by ongoing pain
or marked functional limitations that were not present before illness or
injury. With or without surgery for spinal disorders, pain and concomitant
limitations often linger and, without proper treatment and planning, these
can magnify. The chronic pain management program (CPMP) thus
becomes a truly integral component of treatment in most spine centers.
Such programs, involving many disciplines (most often pain medicine,
PM&R, PT and occupational therapy, and psychology), rely on therapeutic
group milieu to assist patients in learning (and helping each other to learn)
new ways to deal with pain, minimize its impact on their lives, and
overcome psychosocial barriers. Research on the CPMP approach
indicates that patients achieve an average pain reduction of approximately
50%, about 75% are able to get off narcotic medications, and the return to
work rate from such programs is approximately 67%.19 Of course, CPMPs
vary widely in terms of their composition and effectiveness. The spine
center should, at a minimum, be certified by and adhere to the standards
set by the Commission on Accreditation of Rehabilitation Facilities
(CARF) or a similar international organization.

POTENTIAL BENEFITS OF A SPINE SPECIALTY

CLINIC
Many components of treating chronic pain of other origins and back pain
are similar. What, then, is the advantage of having a spine specialty clinic?
Focusing solely on back pain has several potential advantages.
Although in the past, there may have been more separation between
nonsurgical care providers and surgeons, the two can be blended into a
comprehensive system. As reported by Rasmussen et al.,20 the initiation of
multidisciplinary “nonsurgical” spine clinics significantly reduced the
number of lumbar discectomy surgeries performed. One of the factors that
was felt most likely to account for this decline was an improved diagnostic
evaluation process.
Considering the wide range of potential pain origins as well as the
potential and varying roles of psychosocial factors related to back pain, it

5241
is not surprising that patients cover a very broad spectrum of problems and
needs. This gives rise to the need for true multidisciplinary care. It is
imperative that the care providers have, and maintain, a strong and specific
knowledge base regarding spinal disorders. Such skills can only be
developed and continually honed by ongoing interaction with patients,
continuing professional education, and the cross-training provided by the
frequent interaction of professionals from various disciplines caring for
similar patients. This is true not only for the physicians involved in the
clinic but also for the physical therapists and other members of the
treatment team. By building a strong knowledge base in one area,
providers can equip patients with a greater level of education in discussing
their spinal problems and working together toward effective solutions.
Specialized spine centers require a large patient population to support all
the facets required for the multidisciplinary approach to care. Although
some painful conditions are relatively rare, back pain is a very common
problem. Considering that 80% of people have back pain at some point
during their lives and that about 10% go on to develop chronic pain, there
are likely to be large enough patient populations in most communities to
make a spine center a viable undertaking.
The term center of excellence is a determination used in several
specialties to provide quality assurance for new procedures or technologies
or for those surgeries not widely performed, such as video-assisted
thoracic surgery.21 A number of centers of excellence in spine care have
emerged in recent years, but there is no uniform set of criteria used to
define a spine center of excellence. Such centers have a multidisciplinary
treatment philosophy and are committed to providing the highest quality of
care. It is these centers of excellence that should be the lead sites in
developing treatment guidelines, participating in registries, performing
research, and providing education. Implementation of a structured quality
assurance program is a critical element of developing a spine center of
excellence. Designing and implementing guidelines, assessing outcomes,
and implementing changes for improvement may be more manageable in a
spine clinic. This type of program is becoming increasingly needed in this
age of increasing demands for ongoing quality assessment and
reimbursement initiatives such as pay for performance.

5242
 Within the spine clinic, subspecialization will naturally take place.
Based on the interests and skills of the professionals involved with patient
care, various physicians will gravitate toward treatment of specific spinal
disorders. For example, one may take the majority of patients with
unusually challenging cervical spine problems, another may be a leader in
one or more areas of spine arthroplasty, and there should be at least one
surgeon adept at diagnosing the multiply operated failed back patient who
eventually arrives at a spine specialty facility. Some physicians may elect
to perform injections, whereas others do not. There is a need for advanced
interventions such as spinal cord stimulation for pain management. This
type of subspecialization within a spine clinic further provides the care
provider the opportunity to hone highly specialized skills as well as
allowing them to pursue the interventions they are most interested in
providing.
The presence of professionals from multiple disciplines in a spine clinic
will also increase awareness about alternate pain mechanisms and
approaches to treatment. For example, the addition of chiropractic care
providers will increase the awareness of all the care providers of problems
arising from the sacroiliac joint and the role of manipulative therapy in
treating this group of patients with low back pain.

COORDINATION OF CARE
Working one’s way through most health care systems can be daunting for
patients. A comprehensive spine clinic can reduce confusion and anxiety.
Patients can receive a wide variety of services as needed within a single
facility. Patients receiving treatment in a single center will become
familiar with employees, and they will find less redundant paperwork
required for insurance and providing basic history and health data. The
best spine centers provide close coordination of care from one provider to
another through close communication.

RESEARCH AND EDUCATION

If practicing in a university setting, education and research are built into
the framework and environment of patient care. However, the success of
programs still depends strongly on the commitment made by the

5243
individuals involved. Although this is also true in private practice, the
challenges are greater. There is no institutional framework or incentive
built into the practice that promotes involvement in either research or
education. To create a research environment outside the university setting
requires a commitment of time and financial resources. However, a
practice cannot hope to become a spine care center of excellence without
incorporating research and education. The implementation of a research
program is becoming easier with the growing use of electronic medical
records and registry systems in spine care facilities. Establishing an
infrastructure for data collection complements the current demands for
evidence-based medicine and cost-effectiveness information for back pain
interventions. Considering the societal costs associated with back pain,
these demands may be even greater for spine care specialists than for other
disciplines. Although in the past, care providers may have been able to be
successful without engaging in organized data collection, this is likely to
change. Research also provides a venue to gain recognition in the peer
group. This is more easily accomplished in a specialty clinic than in one
spread across multiple specialties, unless focused efforts can be made in
multiple areas.
The increasing use of electronic medical records and national study
registries in spine has greatly facilitated tracking treatment outcomes.
Although these mechanisms are far superior to traditional paper data
collection, they still require time to harvest the data, address unanticipated
scenarios, download, analyze, and prepare reports of the data and write
abstracts and manuscripts. One of the greatest advantages of the registries
is that some are programmed to contact patients by e-mail up to 24 months
after treatment and have patients complete self-assessment forms online
without returning to the clinic. Although radiographic follow-up cannot be
achieved, the patient’s clinical condition can be evaluated.
Another opportunity to become active in spine research is through
participation in clinical trials. To do so is a great responsibility for the
investigator to ensure that the trials are being conducted in accordance to
federal regulations and study protocols. Staff should be hired with
experience in conducting clinical trials, regulatory requirements, and
experience interacting with institutional review boards or human

5244
experimentation ethics committees. Many such trials are financially self-
sustaining, as industry sponsors will provide the funding to cover the cost
of conducting the trial. Participation in such studies provides the
framework for rigorous data collection.
Research is a vital part of quality patient care. Although all care
providers want to take the best care of their patients, without measuring
and being willing to critically appraise their own outcomes, it is impossible
for the individual practitioner to assess and improve the quality of care he
or she is delivering. Through the collection of data and ongoing
assessment of results, problems, such as spikes in particular complication
rates, can be identified and addressed. This is particularly important in a
multiple-physician group to assess the complications and clinical outcomes
of all the care providers in the practice and to ensure that problems are
addressed as soon as they are identified. The emergence of Patient-
Reported Outcome Measurement Instrument System (PROMIS) and its
associated computer-adaptive test (CAT), which strongly correlates with
other “gold standard” spinal outcomes measurement instruments but has a
significantly lower completion time, shows immense promise toward
making this process more seamless.22
Accepting the role of serving as faculty for a residency program or
establishing a fellowship program can also enhance the intellectual
environment of a spine clinic. Such programs often lead to creating lecture
series such as grand rounds and journal clubs, which are relatively
inexpensive. Creating forums for discussion among all care providers in
the group can strengthen the bonds of the practice, allow more insight into
what the other team members’ discipline offer to overall care, and enhance
care by getting the right patient to the right provider more quickly.
Spine specialty centers have the potential to step to the forefront in
shaping the future of spine care on a large-scale basis. Being specialized
and focused in one area makes it easier to participate in registry networks
and other quality improvement initiatives.

Conclusion
The spine is a complex structure that often presents diagnostic dilemmas

5245
and treatment challenges to health care providers. The complexity is
compounded by the frequent and profound psychosocial impact of chronic
spinal disorders. A spine center of excellence must be designed to address
the complexity of these challenges. One of the primary needs is an
organized, deliberately planned approach to the evaluation and treatment
of the broad spectrum of back pain patients. Members of the
multidisciplinary team must be trained and focused on quality spine care.
The use of electronic medical records greatly enhances the ability to track
patients and events related to their care. The team of providers must
understand the role of the other team members and respect what each has
to offer in providing quality care to patients. There must be strong
leadership to keep the team focused, efficient, and effective.
Part of developing a center of excellence is incorporating research and
education. Research efforts can provide patients and practitioners with the
opportunity to participate in clinical trials which can enhance the
reputation of the center in the community while at the same time providing
a means to assess outcomes of various treatments provided in the clinic.
Only through incorporating research can providers have access to the latest
technology and be involved in continually improving the delivery of
patient care. Everyone benefits from education, which can take on many
forms including lectures, journal clubs, conferences, fellowship programs,
and research.

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2. Pincus T, Burton AK, Vogel S, et al. A systematic review of psychological factors as
predictors of chronicity/disability in prospective cohorts of low back pain. Spine
2002;27:E109–E120.
3. Groopman J. How Doctors Think. New York: Houghton Mifflin Company; 2007.
4. Nwosu KC, Bono CM. Incidence of low back pain in athletes and differential diagnosis and
evaluation of the athlete with back and/or leg pain. In: Hecht AC, ed. Spine Injuries in
Athletes. Philadelphia: Wolters Kluwer; 2017:146–153.
5. Strine TW, Hootman JM. US national prevalence and correlates of low back and neck pain
among adults. Arthritis Rheum 2007;57:656–665.
6. Frymoyer JW, Pope MH, Costanza MC, et al. Epidemiologic studies of low-back pain. Spine
(Phila Pa 1976) 1980;5:419–423.
7. Fanuele JC, Birkmeyer NJ, Abdu WA, et al. The impact of spinal problems on the health
status of patients: have we underestimated the effect? Spine 2000;25:1509–1514.
8. Loeser JD, Butler S, Chapman CR, et al. Bonica’s Management of Pain. 3rd ed. Philadelphia:

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 Lippincott Williams & Wilkins; 2001.
9. Scientific approach to the assessment and management of activity-related spinal disorders. A
monograph for clinicians. Report of the Quebec Task Force on Spinal Disorders. Spine
1987;12:S1–S59.
10. Martell BA, O’Connor PG, Kerns RD, et al. Systematic review: opioid treatment for chronic
back pain: prevalence, efficacy, and association with addiction. Ann Intern Med
2007;146:116–127.
11. Hansen RN, Oster G, Edelsberg J, et al. Economic costs of nonmedical use of prescription
opioids. Clin J Pain 2011;27:194–202.
12. Lindsay PG, Wyckoff M. The depression-pain syndrome and its response to antidepressants.
Psychosomatics 1981;22:571–573, 576–577.
13. Fernandez E, Clark TS, Ruddick-Davis D. A framework for conceptualization and assessment
of affective disturbance in pain. In: Block AR, Kremer E, Fernandez E, eds. Handbook of Pain
Syndromes: Biopsychosocial Perspectives. Mahwah, NJ: Lawrence Erlbaum Associates;
1999:123–148.
14. Block AR, Gatchel RJ, Deardorff WW, et al. The Psychology of Spine Surgery. Washington,
DC: American Psychological Association; 2003.
15. Fritz JM, Cleland JA, Brennan GP. Does adherence to the guideline recommendation for
active treatments improve the quality of care for patients with acute low back pain delivered
by physical therapists? Med Care 2007;45:973–980.
16. Wiese M, Krämer J, Bernsmann K, et al. The related outcome and complication rate in
primary lumbar microscopic disc surgery depending on the surgeon’s experience: comparative
studies. Spine J 2004;4:550–556.
17. Regan JJ, McAfee PC, Blumenthal SL, et al. Evaluation of surgical volume and the early
experience with lumbar total disc replacement as part of the investigational device exemption
study of the Charité Artificial Disc. Spine 2006;31:2270–2276.
18. Ozgur BM, Aryan HE, Pimenta L, et al. Extreme Lateral Interbody Fusion (XLIF): a novel
surgical technique for anterior lumbar interbody fusion. Spine J 2006;6:435–443.
19. Turk DC, Burwinkle TM. Assessment of chronic pain in rehabilitation: outcomes measures in
clinical trials and clinical practice. Rehabil Psychol 2005;50:56–64.
20. Rasmussen C, Nielsen GL, Hansen VK, et al. Rates of lumbar disc surgery before and after
implementation of multidisciplinary nonsurgical spine clinics. Spine 2005;30:2469–2473.
21. Chin CS, Swanson SJ. Video-assisted thoracic surgery lobectomy: centers of excellence or
excellence of centers? Thorac Surg Clin 2008;18:263–268.
22. Hung M, Hon SD, Franklin JD, et al. Psychometric properties of the PROMIS physical
function item bank in patients with spinal disorders. Spine (Phila PA 1976) 2014;39:158–163.

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CHAPTER 108
Pain Management in Primary Care
WILLIAM C. BECKER and MATTHEW J. BAIR

Introduction
PREVALENCE OF PAIN IN THE UNITED STATES
Pain is the most common reason cited for patients seeking medical care,
and pain accounts for up to 80% of total visits to physicians’ offices.1,2
Although it is difficult to determine the prevalence of pain precisely,
recent surveys suggest that 75 to 105 million Americans experience pain
daily or intermittently.3–5 Given this widespread prevalence, the Institute
of Medicine (now the National Academy of Medicine)6 and the U.S.
Department of Health and Human Services,7 among other important
stakeholder groups, have called primary care the foundation of pain
treatment in the United States, a foundation that should be adequately
trained to meet the challenge of delivering high-quality pain care.

ECONOMIC IMPLICATIONS OF CHRONIC PAIN

The National Academy of Medicine estimated the cost of pain to be
approximately $565 billion dollars, making it one of the costliest
conditions in the United States. Although the precise figure has been
debated, there is little argument that the costs associated with pain
treatment and the economic impact of missed days of work and
unemployment and other societal costs are high and increasing.
Care management plans and disease management programs are
abundant for other chronic conditions, such as asthma, hypertension,
hyperlipidemia, and diabetes mellitus. Treatment strategies include case
management, treatment algorithms, provider education, and patient support
groups. In contrast, very little emphasis has been placed on studying and
developing such initiatives for chronic pain conditions. Given the large
allocation of United States health care dollars for treating patients with

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these conditions, it is time for the provider, payer, and policymaker
communities to take notice; emerging models discussed at the end of this
chapter may signal the beginning of a promising trend.

CHRONIC PAIN MANAGEMENT: THE STATUS QUO

With the onset of pain, most patients attempt self-care with over-the-
counter products and/or self-help techniques (e.g., distracting activities,
rest). When these methods fail to provide adequate relief, the patient
generally seeks help from a medical professional. In many cases and
particularly in health care systems with limited access to specialty care, the
gatekeeping primary care provider is the first medical contact. The primary
care provider recommends treatment and refers the patient for appropriate
specialty care, such as a physical medicine assessment for low back pain.
When pain becomes chronic and specialty care is ineffective in
improving the underlying condition, care management becomes more
difficult. In a recent survey, only 34% of internists reported that they felt
comfortable with their abilities to manage patients with chronic pain.2 In a
related article, Ballantyne and Mao8 wrote that the most difficult issue now
facing physicians is “whether and how to prescribe opioid therapy for
chronic pain that is not associated with terminal disease, including pain
experienced by the increasing number of patients with cancer in
remission.” In part, physicians are hesitant to prescribe opioids because
they lack both the understanding of how to comprehensively assess pain
and its common comorbidities and the knowledge of available pain
therapies.
The varied presentations and manifestations of chronic pain may at
times confound primary care providers. Physical exam and radiographic
abnormalities are not predictive of pain severity or dysfunction.9 Many
patients experience pain that may be constant and occurs for several years,
and yet their life functioning is not changed in major ways. Conversely,
there are other patients with similar structural abnormalities who suffer
substantially more and cannot maintain their usual levels of activity.10
Patients whose lives are significantly disrupted by pain engage in
behaviors that are maladaptive, anticipate more distress, amplify
sensations associated with pain, spend more time resting, and complain of

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less ability to control pain.11,12 It may be reassuring to providers to
recognize that this same degree of variability is seen in virtually all chronic
conditions as a manifestation of the complex interplay of biologic,
psychological, and social factors.
At the same time, surveys evaluating the adequacy of pain treatment
demonstrate that the current system is dysfunctional.13 Patients report that
they are not asked about pain, that they are afraid to report pain to their
primary care providers, and that they are often not offered treatment. In
one survey, 22% of patients with pain reported being uncomfortable
discussing pain with their personal physicians, 13% said they were denied
pain medication or referrals to pain specialists, and 70% reported
experiencing continued pain despite treatment.14 Much of these system
problems can be attributed to the treatment of pain at the primary care
level.

SEARCHING FOR SOLUTIONS

There have been tremendous advances in the knowledge of pain
pathophysiology, the understanding of treatments for pain, and recognition
of the value of an interdisciplinary approach to pain management. On the
scientific front, there has been an explosion in pain research, and new
pharmaceutical agents have become available for treating different types
of pain. Complementary and integrative health therapies for pain
management have gained recognition and an increasingly robust evidence
base. Novel interventional techniques and surgeries have been introduced.
Professional pain societies have sprung up, and training is now available to
provide physicians and other health care professionals with expertise in
pain management. Despite this unprecedented progress, pain care remains
inadequate, and undertreatment of pain is still considered pandemic. The
reasons for these continuing inadequacies are varied, but it is clear that
new solutions must focus on primary care.

A New Approach to Chronic Pain Management

There are many different types of pain that it is difficult for a nonexpert
provider to become familiar with and comfortable treating all pain

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conditions. Current categories for classifying pain include nociceptive
versus neuropathic, acute versus persistent, cancer versus noncancer, and
area of the body (headache, abdominal pain, chest pain). These categories
are simplistic and helpful only in a general way.
We are accustomed to accepted, well-defined, objective measurements
to assess the quality of care. For many other chronic conditions, there are
standardized outcome measures. In patients with diabetes, we can measure
hemoglobin A1C levels. In patients with asthma, peak flow and the use of
inhaled β agonists guide care. Treatment outcomes for pain are often
subjective, confusing, and controversial. If a patient’s pain severity is
better but function is not improved, is this outcome adequate? If the patient
is satisfied with treatment but pain intensity levels remain high (e.g., an 8
on the 0 to 10 pain numerical rating scale), is this treatment sufficient? If
the patient returns to work but is on high doses of opioids, is this
acceptable? All of these questions frequently arise in the primary care and
complicate treatment.

WHO TREATS CHRONIC ILLNESS?

When pain becomes chronic, a behavioral syndrome and comorbidities
may emerge including depression, anxiety, helplessness, insomnia,
deconditioning, and increased reliance on the health care system, what has
been called “high-impact” chronic pain. At this point, chronic pain
becomes a disease process that needs chronic disease management.15
Chronic back pain is not a diagnosis but rather a description of duration
and location. In many cases, it is not possible to be more precise in the
diagnosis of, for example, low back pain because even experts disagree on
the underlying etiology.16 Neuroscience increasingly points to
dysregulated neuroplasticity and central sensitization as common pathways
to chronic pain,17 further underscoring the futility of “imaging” chronic
pain in most cases. Providers would do well to learn to message to patients
that a lack of imaging findings is important for ruling out sinister causes of
pain (e.g., cancer) but does not mean the pain is not real.
Failure to be more precise in the diagnosis should not delay treatment or
impede medical management. Treatment in primary care often involves
uncertainty, as most of the conditions encountered cannot be diagnosed

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precisely: Viral illness, rash, or headaches are common, and the etiology
unexplained. Chronic pain falls into the group of conditions that often
defies definitive diagnosis and is suited to the primary care practice. A
patient’s suffering can be ameliorated by nonpharmacologic interventions
including patient education and self-management skills that may be
combined with analgesics such as nonsteroidal anti-inflammatory drugs
(NSAIDs).
All primary care physicians must treat patients with a variety of chronic
diseases. In fact, most chronic illness is principally managed at the primary
care level.18 Improvements in the medical management of asthma,
hypertension, and diabetes have arisen from interventions implemented in
primary care. Despite the lack of specialty training and through the use of
practice guidelines, following treatment recommendations, conducting
chart reviews, discussing shared experience, and providing expert
assistance, primary care delivers excellent medical care. Management of
persistent pain lends itself to the same paradigm.

WHY PRIMARY CARE IS INVOLVED?

Primary care is based on the elements of trust, therapeutic alliance,
advocacy, continuity, care coordination, preventive care, and careful
attention to quality of life/lifestyle issues. Motivating patients to strive for
better health through exercise, diet, stress management, medication
adherence, and disease monitoring is a common role played by the primary
care provider—a role that requires the provider to adopt and maintain a
nonjudgmental attitude.
Primary care is uniquely positioned to provide care for patients with
chronic pain. Of all specialties, primary care providers have the largest
geographic distribution. Rather than clustering around medical centers in
the largest cities, they are broadly distributed over diverse communities—
from urban clinics to suburban medical centers to private practices in small
towns and rural areas. Furthermore, primary care providers are trained in
patient-centered communication, biopsychosocial assessment, and
multimodal treatment planning, all core features of a high-quality approach
to chronic pain.
By its very nature, primary care entails continuity by developing a

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longitudinal experience with patients. Each office visit enables the
provider to achieve greater understanding of how individual patients are
dealing with their persistent pain. Primary care providers are experienced
in providing comfort and disease management for chronic conditions.
When clinicians are challenged to broaden their definition of pain as a
symptom and begin to view it as a chronic illness,11 primary care is well
equipped to deal with chronic pain.
When a patient’s pain becomes persistent and specialty care is either
unavailable or ineffective as a treatment option, the providers can continue
to play a key role by coordinating care, intervening when symptoms
change, and constantly encouraging patients to make lifestyle choices as
they do in all other chronic diseases: weight loss, sleep hygiene,
anxiety/depression/mood management, physical activity, education, and
judicious use of medications.19
From a cost and utilization perspective, primary care is the most
appropriate setting for chronic pain management. Most types of health
insurance, as well as Medicare and Medicaid, cover primary care visits yet
may not cover long-term psychosocial treatment or interventional
procedures. A classic 1995 study of low back pain examined 1,555
patients cared for by chiropractors, orthopedic surgeons, or primary care
providers. Cost, work status, and time to restoration of baseline status were
monitored. All groups achieved similar outcomes yet primary care was the
least costly.20 Risks of polypharmacy are better managed within the
primary care structure because it is accustomed to dealing with multiple
diseases and their treatments in a single patient.

TREATING CHRONIC PAIN IN THE PRIMARY CARE

SETTING—WHY A CHALLENGE?
Training in Pain
Much of formal medical training occurs in hospitals where acute
symptoms and life-threatening conditions are studied. Historically, very
little practice has been offered in the management of chronic pain in the
outpatient setting. Training in pain management may be limited to a brief
session in a pharmacology or neuroanatomy course during medical school.
As a consequence of this limited training, many residency-trained primary

5253
care providers are ill equipped and therefore uncomfortable treating
patients with persistent pain.21 This may lead to inadequate assessment,
substandard treatment planning, poor follow-up and monitoring, and
generally poor quality of care.
However, the opioid crisis has prompted medical schools to re-examine
pain management curricula and has spurred widespread calls for medical
student and provider education to be cornerstones in addressing the crisis.

Disagreement among Experts—To Treat and Not to Treat

In recognition of the need to improve pain management, the Federation of
State Medical Boards issued guidelines on the appropriate workup and
treatment of persistent pain.22 Most states have adopted the Federation’s
recommendations in the form of Intractable Pain Tratement Acts. The safe
and proper use of opioids is the cornerstone of these acts, encouraging
providers to assess patients’ pain and use medication when necessary.
Increasingly, adequate pain relief is being viewed as a patient’s right—and
a clinician’s obligation—sometimes to the point of allowing the patient or
family to take legal action against doctors for the undertreatment of pain.
On the other hand, the opioid crisis has ushered in a new era of caution in
treating pain.
The Centers for Disease Control and Prevention (CDC) released the
Guideline for Prescribing Opioids for Chronic Pain in March 2016,23 a
landmark effort that garnered widespread publicity and spurned heated
discussions of controversies related to guideline recommendations. For
example, the CDC guideline contrasted significantly to the 2009 American
Pain Society/American Academy of Pain Management’s Clinical
Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer
Pain24 as decidedly “opioid avoidant.” The CDC guideline promoted
nonopioid analgesics and nonpharmacologic treatment options as preferred
in the treatment of chronic pain, identified recommended limits in opioid
doses prescribed, and advocated for heightened vigilance and monitoring
for indications to taper down or discontinue opioids especially among
patients already on long-term opioid therapy when benefits no longer
outweigh harms. The CDC guideline also emphasized the lack of evidence
demonstrating long-term efficacy of long-term opioid therapy in contrast

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to other treatments for chronic pain25 and the growing evidence of
potential harms, especially at higher doses.
It is too early to tell the full impact of the CDC guideline. However, the
CDC guideline has already changed many providers’ approach to opioid
therapy specifically and chronic pain care generally. More providers
appreciate that high-quality pain care involves a combination of
nonpharmacologic and pharmacologic options. Treatments where patients
take an active role (e.g., yoga) are viewed as particularly valuable. Pain
self-management skill building is considered low cost and effective and
promotes less reliance on the health care system and that it may be in
patients’ best interests to reduce or avoid taking opioids, especially long
term. Avoiding long-term opioid therapy has been informed by consistent
observational data and emerging randomized controlled trial (RCT) data
that patients may experience accelerated decline in well-being and accrue a
variety of bothersome and sometimes serious harms on long-term, and
especially high-dose, opioids. That said, for individuals already on long-
term opioid therapy for whom benefit is outweighing harm, the therapy
(and ongoing close monitoring of it) should be continued. Involuntary
tapering of patients not experiencing harm is not evidence based, not
patient centered, and may have its own set of serious risks and unintended
consequences.26

Barriers to Treating Pain

Many barriers to the management of pain have been welldocumented in
this text and others.27 These obstacles relate to the medical system,
providers, patients, and regulatory and governmental agencies, all of which
are operant in primary care practices. At the same time, other obstacles are
unique to primary care, making pain management more difficult even for
the well-trained, conscientious provider.

Time Constraints
Primary care providers often perceive pressure to do more in less time,
especially in light of cuts in reimbursement (Medicare, Medicaid, and
other types of commercial insurance). Furthermore, the typical 15-minute
office visits are crowded by other activities: telephone calls, add-on

5255
appointments, emergencies, hospital admissions, serving as preceptor for
students or midlevel providers (i.e., interns, residents, nurse practitioners),
and reviewing laboratory and x-ray reports.
Patient complexity is also a major contributor to time constraints.
Patients may present with multiple medical issues at each visit—ranging
from chronic conditions (diabetes, hypertension, and
hypercholesterolemia), situational issues (insomnia, stress at work,
menopausal symptoms), preventive care needs (immunizations, cancer
screening), procedural needs (skin tag removal, knee injections), and other
issues (medication refills, disability forms, jury excuses).
Comprehensive assessment and documentation of pain would be
difficult in this setting even if the entire 15 minutes were available to
address pain during the visit. To address these issues but still harness the
wealth of resources that make primary care such a compelling foundational
treatment setting, promising new care models described in the following
discussion have emerged.

Lack of Guidelines Specific to Primary Care

A variety of well-recognized treatment algorithms and evidencebased
guidelines exist for treating other chronic conditions encountered by
primary care physicians (e.g., cancer,28 neuropathy,29 fibromyalgia
syndrome30). Although guidelines have been developed for some pain
problems, there are relatively few specific recommendations for the
treatment of persistent pain and rarely address the practical challenges to
managing chronic pain in primary care.
Even when guidelines are available, studies show that often they are not
followed by clinicians.31 This can be explained in part by the nature of
chronic pain. When a patient’s chronic pain worsens, the cause is
frequently undiscoverable, making it difficult to apply a guideline or to
decide on a different treatment when so many therapeutic options have
been ineffective.

Patient Nonadherence to Treatment

In other diseases, the consequences of nonadherence are not apparent to
the patient. Patients with worsening atherosclerosis, hypertension, or
diabetes are often asymptomatic. In contrast, nonadherence to medical

5256
management has serious implications for patients with persistent pain and
their physicians. Detriments to patients’ pain intensity, functional status,
quality of life, and mental health conditions may occur as a result to
nonadherence.

Specialty Referrals
Referrals for patients with persistent pain may differ for other conditions
in primary care practice. After referrals to specialists in other conditions,
patients may return to the primary care provider after the medical issue has
resolved or the chronic illness has an expected treatment course. Some
examples include dysfunctional uterine bleeding is diagnosed and treated
before referral back to primary care. The fractured bone is set and
stabilized, rehabilitation is arranged, and the patient presents back to
primary care with restored function. The patient with congestive heart
failure has further diagnostic testing, medication adjustments, and returns
to primary care when symptoms have improved and the patient is stable.
The workup and treatment of the patient with persistent pain, on the
other hand, may be less amenable to these clear benefits and resolution of
symptoms. The acupuncturist diagnoses an imbalance of energy or “chi”
and treats with needles and herbs. The physiatrist may focus on muscle
tightness and nerve injury and offers rehabilitative therapies. The
interventionalist uses injections to alleviate radicular pain. The
chiropractor focuses on structural imbalance of the skeleton and offers
manipulation therapy.
Often, the diagnoses and procedures for chronic pain are less familiar to
the primary care provider (e.g., disk disruption, discogram, vertebroplasty,
facet arthritis, radiofrequency ablation). Unfamiliar drugs and drug
combinations are uncomfortable for physicians to prescribe and monitor.
These may include polypharmacy with four or five drugs, such as
combinations of multiple anticonvulsants (gabapentinoids), serotonin
norepinephrine reuptake inhibitors, multiple opioids, and/or other
analgesics; drugs rarely prescribed (e.g., methadone); and doses not used
(e.g., high-dose opioids or gabapentin). After referral, patients may return
to primary care with unclear parameters on what constitutes treatment
“success.” Too often, the patient’s pain level is as high as when first
referred for specialty care, and psychosocial issues such as depression and

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anxiety may not have been addressed.

Comorbid Conditions
The most commonly occurring comorbid conditions in patients with
persistent pain are depression, anxiety, insomnia, and substance misuse or
substance use disorders.32 These comorbidities complicate care. Patients
may resist psychiatric care for many reasons including the perceived
stigma, the additional cost, or the belief that their pain is unrelated to their
mental health comorbidities.
Pain can make depression worse, and depression can make pain worse,
both independently.33 Patients seeking relief from their pain and comorbid
conditions may self-medicate with alcohol and other substances such as
marijuana, which can further complicate the problem. They may take
prescribed pain medications to treat the comorbid condition and
temporarily relieve their symptoms but can make them feel worse long
term.
Failure to address underlying anxiety, depression, insomnia, and
substance use disorders makes pain treatment more difficult. These
comorbid conditions are difficult to treat in stable patients. When
persistent pain or a chronic illness is also present, the treatment is even
more complicated because the pain experience is more severe and less
amenable to treatment. It is unlikely that a simple, single-drug regimen or
series of epidural steroid injections will be the long-term solution for
chronic pain and comorbid conditions.

Adversarial Relationship
Medical practice in primary care is built on trust, respect, and advocacy for
the patient. The doctor–patient relationship is fundamental and develops
over years of providing preventive care, treating acute conditions, and
supporting the patient through life transitions such as the birth of a child,
unemployment, and the death of a close family member. This long-term
relationship enables the primary care provider to better understand the
patient as an individual and allows the provider to more effectively share
medical advice and decisions with their patients.
Persistent pain may disrupt this stable pattern and create an unusual
relationship that may not emerge in the management of other chronic

5258
diseases. The primary care provider may, at times, feel forced into an
uncomfortable adversarial position that he or she is not well trained to
manage. Patients with chronic pain ask for many things that are not
guideline concordant at times the physician must argue against or deny
certain diagnostic tests or treatments. For example, the patient wants the
doctor to order additional or repeated expensive procedures (e.g., magnetic
resonance imaging [MRI]) when his or her pain worsens. The doctor
refuses because it is not consistent with guidelines, will not change the
treatment plan or lead to a cure for the persistent pain, or is not approved
by the patient’s health insurance plan.
In this scenario, the provider may find themselves in the difficult role of
contradicting the patient’s wishes. When the doctor is unable to be
supportive, the patient begins to question whether his or her “advocate”
still wants to help. The patient–provider relationship may become strained,
and the patient may resist potentially beneficial treatment options
recommended.

Addressing Barriers to Care

As mentioned earlier in this chapter, primary care providers may lack
comfort and confidence in managing chronic pain. In addition to limited
training, there are a number of other underlying reasons for this.

MYTHS AND BIASES

Patients—Without conscious intention, people attach meaning to all
sensory experiences. The smell of a rose may hold a special meaning to
someone who received her first bouquet for the high school prom. The
sound of the musical tune “Jingle Bells” may signify happiness, family
gatherings, and holiday gifts. Pain, especially when it is persistent, often
conveys a sense that the person is being punished for some real or
perceived infraction.
Too often, patients with chronic pain believe that they suffer because of
some mistake they made or that pain is to be expected as a part of aging.
At times, there is so much salience attached to pain that it is difficult to
convince the patient otherwise. These beliefs about “needing pain” or
“deserving pain” complicate treatment.

5259
 Providers—Primary care providers may be suspicious of patients who
complain of pain. Physicians understand certain types of pain—cancer
pain, end-of-life pain, or acute trauma/illness pain—but are less accepting
of the persistent pain that has few objective signs of defined conditions.
We ask, “Why do some patients complain while others, with the same
pathology or anatomy, do not complain?” “What is the secondary gain?”
“Is this pain real?”
Some providers still cling to the outdated notion that most causes of
chronic pain should clearly be identifiable on imaging studies. When pain
is not easily explained in this paradigm, bias may lead the primary care
provider to suspect mental health causes. In addition, mental health
comorbidities are common with persistent pain. The primary care provider
may believe that the persistence of the pain relates directly to the patient’s
depression or anxiety, thereby depreciating the pain complaint. Patients
perceive this attitude as devaluing their experience.

PATIENT RESISTANCE
The false dichotomy of physical pain versus emotional pain, still often
perpetuated by health care providers, affects patients’ experiences as well.
The patient reasons, “If my doctor cannot find anything wrong with me
and if there is no fix for my situation, he or she will assume that I must be
crazy.” For this reason, feelings such as “you think this is all in my head”
are often expressed in patient encounters.
In fact, physical and emotional pain cannot be separated. They coexist
and feed on each other. For instance, the most balanced, rational, and
accepting patients can still experience high pain levels from fibromyalgia
syndrome even when anatomic pathology is lacking on physical exam or
diagnostic studies. As noted earlier, advances in neuroscience have
elucidated pathways that explain this phenomenon.
Despite wide recognition that mental health comorbidities frequently
coexist, patients often resist the suggestion that anxiety and depression
may be exacerbating their pain. They equate these diagnoses with hysteria
or hypochondria and feel that the physician is depreciating their pain
experience. Treating comorbidities is difficult in this setting, especially for
providers with inadequate training.

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REGULATORY SCRUTINY
Fear of regulatory scrutiny is common in primary care settings, although in
reality, very few primary care physician practices are ever investigated by
regulatory bodies. Even fewer practices have had their licensure
suspended. These few cases and those covered in the media often involve
high-profile providers or illegal and unethical activities. Despite this fact,
reality sometimes does not mitigate perception, and regulatory scrutiny, as
noted in a previous chapter by Gilson in this text, continues to impede
more aggressive pain management in many primary care practices.

PATIENT EXPECTATIONS
The paternalistic relationship commonly seen in medical practice is being
challenged by consumer activism. Patients have more access to health
information than ever before. They have more time and motivation to
research their conditions on the Internet and may sometimes know (or
believe they know) more about treatment options and a particular disease
process than their primary care physician. As is often the case, this is a
mixed blessing. On the one hand, an informed patient may be much more
amenable to self-management. In some cases, however, an informed
patient may have misguided beliefs based on less reputable information
sources.
Most patients with persistent pain do best after learning and adopting
self-management skills. Acceptance of their chronic condition, developing
strategies including conditioning exercises, and making changes in work or
hobbies lead to the best results. However, when information-seeking
patients are confronted with “miraculous cures” and daily news articles
touting advancements in pain treatment, adapting to pain is difficult for the
provider to sell. Too often, patients find themselves on a constant search
for the next cure or “fix” only to be disappointed when it fails and then
moving on to the next “harmless, 100% effective” treatment. As this
pattern repeats over and over, the best treatment—acceptance, adaptation,
and conditioning—is delayed. The expectations of desperate patients
seeking miracle cures create significant barriers to optimal care.

Pain Practitioner: A Primary Care Model

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TRAINING
As in other disciplines, training received by primary care providers may
become outdated as new knowledge is accumulated and scientific
advancements are achieved. Education in all areas of medicine must be
lifelong and constantly updated. Medical training provides a knowledge
base with courses in neuroanatomy, pathophysiology, and
pharmacokinetics. This training serves primarily as a foundation and a
method for learning and applying new knowledge.
The process of learning and reapplying new knowledge is well accepted
in medicine. Despite all the practice management issues and the multilevel
barriers to pain care, primary care providers continue to learn and apply
new information in their daily clinical practice.

COLLABORATION WITH PAIN SPECIALISTS

Complex conditions are always better managed when primary care
providers and specialists have open lines of communication and clearly
delineated systems for coordinating care; pain care is of course no
different. For their part, informed and collaborative pain specialists trained
in the biopsychosocial approach to pain can be a great asset to primary
care by guiding primary care physicians through learning new skills and
providing direction regarding when to refer patients back for further
specialty care. Such constructive communication can lead to greater self-
assurance and competence among primary care physicians as they manage
complex pain patients in their practices.

NEW FOCUS
Patients with persistent pain have similarities and differences from patients
with other chronic illnesses. They both have chronic conditions where cure
is unlikely. Self-management is the key to reaching treatment goals. Denial
about the disease and nonadherence to treatment recommendations are
common and expected challenges for the provider.
On the other hand, mental health issues are more common in persistent
pain and interfere with treatment. Patients may resist psychosocial
diagnosis and interventions. Long-term opioid management can be
challenging for the patient and the provider. Nonadherence to treatment

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recommendations increases morbidity and mortality in diabetes,
hypertension, and congestive heart failure. In chronic pain, nonadherence
increases the clinicians’ work stress, by requiring more office visits,
documentation, and medication surveillance. Although regulatory scrutiny
does not occur often, the perception of legal difficulties increases practice
discomfort.
In managing pain, it is important for the physician to understand that
pain scores are subjective and that a stronger focus should be placed on
function. Although measuring pain is important and mandated in a variety
of settings,34 the physician must not lose sight of the agreed on goals of
treatment.
A new pain complaint or worsening symptoms do not necessarily
mandate more medication. In treating diabetes, a worsening glycated
hemoglobin (HgBA1C) leads the physician to recommend adjustments in
diet, exercise, and medication. Similarly, in treating chronic pain,
recommendations should take into consideration life stressors, pacing daily
activities, depression, anxiety, and worsening of underlying pathology as
well as medication. When the primary care provider understands that an
increase in pain does not necessarily mean increasing the patient’s
medications, treatment issues may become easier.

ASSESSMENT AND EVALUATION DURING SHORT

VISITS
Given the typically short office visit and the many pressures on the
physician’s time, chronic illness management is becoming more difficult.
In the typical 15-minute appointment, the patient with low back pain must
be evaluated, but he or she may have other conditions requiring
assessment, such as hypertension, diabetes, a sleep disorder, and fatigue
that are also bothersome to the patient and they want addressed. Given an
hour for the evaluation and adequate support staff, primary care physicians
would all be better pain managers. But given a short time, stressed, and
overworked support staff and patients with sometimes myriad complex
conditions to be addressed, this is not the case.
Despite the reality of a busy office schedule, primary care is uniquely
positioned to take care of the patients with chronic pain. We know our

5263
patients through associations developed over years of repeated exposure at
routine medical care. We understand our patient’s coping strategies, family
dynamics, and work stresses. The solution to the dilemma lies in making
the typical short office visit more effective for patients needing chronic
pain management.

THE 15-MINUTE OFFICE VISIT

Validating the Patient
Validation is straightforward when a patient presents with an ankle sprain
or a sore back. The injury is easily identified by the history, and the
diagnosis is easily confirmed by physical examination. Diagnostic imaging
and/or laboratory reports further support the physician’s initial impression,
and the patient’s chief complaint and the associated pain improve steadily
with a short course of uncomplicated therapies—an NSAID, muscle
relaxant, application of cold or heat, and rest.
Validation poses problems for primary care when the patient suffers
from chronic pain. We are concerned that the patient will request
something we cannot deliver, such as total pain relief, additional MRI
studies, or unsafe doses of medication. The evidence shows that, in fact,
clear, nonjargon-laden, nonjudgmental education makes pain care planning
easier. In a study of patients with fibromyalgia syndrome, providing the
patient with a diagnosis resulted in the patient making fewer visits to the
physician’s office and becoming more empowered and proactive.35
Once the patient understands that we believe the pain is real, more time
can be spent dealing with symptom control, exercise, and other important
management issues. At each office visit, make sure that the following steps
have been taken:
• Ask about pain intensity but more importantly, painrelated functional
interference.
• Determine the functional status of the patient and whether the
treatment is improving function.
• Modify the treatment according the patient’s response.
• Use a combination of nonpharmacologic and pharmacologic methods
for pain control.
• Explain the available options and foster a positive attitude in the

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 patient toward dealing with the pain.
• Normalize the interrelationship between mood and pain and help the
patient understand that managing mood disorders and other comorbid
conditions will also help the experience of pain and thereby improve
quality of life.
Having a set routine with these key goals in mind sets the agenda and
can streamline even a difficult, complex visit.

Assessment Tools
Chronic pain usually starts as an acute pain episode. In most cases, the
acute episode resolves and the patient returns to normal function. Even
fibromyalgia syndrome, defined as widespread pain for months to years,
has a beginning. The workup and treatment can take months before the
correct diagnosis is discovered, and the physician becomes aware that the
problem is long term and likely to present problems in management.
At this point, the physician’s attention should focus on chronic disease
management (i.e., symptom improvement rather than multiple
interventions and cure). How can the physician best do this evaluation in a
short office visit? Referral may or may not be an option as specialty
referral may not be available, too expensive, and time-consuming for many
patients. Evaluation needs to be focused on the desired outcome of pain
reduction, functional improvement, and identification and management of
comorbidities. Because such an evaluation can easily take up several visits,
handouts and questionnaires can be very useful (i.e., The Initial Pain
Assessment Tool, Pain Disability Index, Quality of Life Scale, Patient
Health Questionnaire-9, Generalized Anxiety Disorder 7 [GAD-7], Zung
Self-Rating Depression Scale, and Function and Goal Setting).
Try giving the patient self-assessment forms that measure pain,
function, depression, and anxiety and allow the patient to complete the
assignment at home. Patients tend to like these questionnaires because they
permit patients to describe in detail issues that the physician may not have
the time to elicit during the office visit.
A follow-up visit is designed to review the results with the patient. The
handouts direct the follow-up visit to the important outcome variables:
pain and function. They are helpful in that they let the patient know which

5265
outcomes are most important and what each subsequent office visit will
address. The patient who demonstrates anxiety or depression on the self-
reported questionnaire is more likely to accept treatment, making
discussion and treatment of such comorbidities less time-consuming.
Assessment is covered in detail elsewhere in this text.

Substance Misuse Screening

Primary care physicians are often hesitant to prescribe opioids. When
treating patients with chronic pain, such caution is justified as long-term
opioid therapy often offers modest or no benefit, usually involves
bothersome side effects, and may lead to serious adverse effects.
Substance misuse, particularly involving opioids, is an important
comorbidity in chronic pain management. Fortunately, there are multiple
questionnaires available to help assess this risk. Commonly used screening
tools practical in primary care include The Screener and Opioid
Assessment for Patients with Pain,36 Opioid Risk Tool,37 and Drug Abuse
Screening Test.38 Patients who score high on any of these scales are more
likely to misuse opioids. If referral to a pain management specialist is an
option, the primary care physician might consider this. Such screening is
also covered fully elsewhere in this text.

Goal Setting and Plan of Action

Like other chronic illnesses, patient participation and adherence to
treatment recommendations predict better outcomes. Chronic pain affects
many life activities and, in turn, quality of life. Goal-setting discussions
direct the patient to improved activity and a targeted outcome. For
example, if the patient wants and agrees to spend more time out of bed,
walk 10 minutes a day, or work in the garden, any of these might serve as
a goal that can be tracked with each visit. As patients begin to anticipate
the questions the physician will ask about their goals, visits become more
streamlined and focused on a functional outcome.
After the patient has been evaluated and treatment has been initiated,
adequate follow-up of a patient with chronic pain can be difficult to
accomplish in a 15-minute visit. Follow-up does not take as much time
when the physician stays focused on the desired functional outcome.

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Consider a routine follow-up for a patient with diabetes. We begin by
asking about diet, exercise, foot numbness, vision, and home glucose
monitoring. We review the self-monitoring results and then perform a
physical exam focused on the blood pressure, eyes, heart, and
monofilament exam of the feet. We review the HgBA1C, microalbumin,
and low-density lipoprotein. We ensure that the patient is taking
recommended medications. We change treatment based on all the
information received. All of this is done every day with our patients with
diabetes and at each visit; all of this can be accomplished in 15 minutes.
The difference in managing chronic pain, and the reason that visits
consume more time, is that often it is unclear what to follow, what to ask,
and what outcomes to track at each visit. It is vital that each follow-up
session remains focused on symptom management and functional
improvement. A patient’s pain diary or journal can be helpful in focusing
follow-up visits. Pain diaries, available in paper and electronic form, are
similar to regular diaries except that the entries focus on pain. Patients
record pain-related elements such as the time pain was experiences, pain
characteristics (e.g., burning, stabbing, aching), the location of the pain,
what he or she did to alleviate the pain, and whether what they did helped.
The patient brings the pain diary to each follow-up session, focusing the
visit on a particular pain score and whether the recommended treatment
was effective.
Activity and sleep questionnaires are also helpful in concentrating the
appointment on these quality of life issues. In a mutual goal-setting
discussion with the patient, the questions can revolve around previously
agreed on and previously documented functional outcomes such as the
amount of time spent out of bed, the 10-minute walk, or the time spent
working in the garden.
Charts reviewed of primary care visits in patients with pain frequently
demonstrate a failure of adequate documentation.39 Given the time
pressures, it is no wonder that documentation often is low on our list of
priorities. Handouts and questionnaires filed in the patient’s chart enhance
this record keeping and save time.

PHARMACOLOGIC TREATMENT

5267
There are many pharmacologic treatment options for persistent pain.
Pharmacology in primary care is difficult because of the many treatment
choices, the lack of agreement among experts, and the nearly complete
absence of data from pragmatic studies where patients have multiple
comorbidities and are on multiple medications for other conditions. How
and why a particular medication is used in a patient with pain varies based
on pain severity, diagnosis, and many other factors. U.S. Food and Drug
Administration-approved drugs or randomized trial results could guide
prescribing. Primary care often uses past experience even when this
experience is inaccurate or inappropriate. An example of this is the
common use of ineffective nonsteroidal anti-inflammatory medications in
neuropathic pain treatment in the primary care office.40
Access to medication is also a major force in pharmacologic options in
the primary care setting. Nonformulary drugs or third-tier medications
requiring high patient copays are a significant factor in prescribing. If the
primary care provider has to obtain a preauthorization or justify a
prescription, the medication may not be prescribed because this extra step
requires excessive time.
As the Ballantyne and Mao8 article points out, opioid prescribing is one
of the most difficult decisions facing primary care in managing persistent
pain. When prescribing opioids for pain management, physicians are often
faced with scenarios that mirror those we associate with addiction: early
refills, lost or stolen medication, borrowed medication, and urine drug tests
that are inconsistent with current therapy. In these cases, documentation is
critical. Strategies such as the five As of treatment success enable the
primary care physician to concentrate on the outcomes that are essential to
the patient’s overall quality of life (Table 108.1).41

TABLE 108.1 The Five As of Treatment Success

A-1 = Analgesia or pain score
A variety of pain scales are available in multiple languages. Pain measurement is the first
element in evaluating successful treatment.
A-2 = Activities of daily living or functional outcome that is meaningful to the patient
At the initial and subsequent visits, work activities, household duties, social activities, hobbies,
and physical exercise target are recorded and goal setting is discussed. When treating any
chronic condition, follow-up visits are necessary to evaluate the effectiveness of the treatment.
A-3 = Adverse events

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 Anticipating and soliciting feedback from the patient regarding side effects from treatment
allows the physician to proactively manage adverse events rather.
A-4 = Aberrant behavior
Patients on long-term opioid therapy may display behaviors that raise concerns, including early
refill requests or using analgesic medication with unprescribed controlled substances or illicit
substances. When such patient behavior occurs, careful interpretation is needed. Document the
behavior in the patient’s chart, discuss it with the patient, and come to a mutual understanding
of what action will be taken if the behavior occurs again.
A-5 = Adherence to the treatment plan
Providers should engage patients in a shared decision-making process to arrive at a feasible,
acceptable multimodal pain care plan that has at its foundation active pain self-management.
Providers should follow-up with patients about adherence to that plan to troubleshoot barriers
and coach and motivate patients to greater adherence to the agreed on plan.

REFERRAL TO AN ADDICTION SPECIALIST

When to refer a patient to specialty care may be a difficult question and is
highly variable among different practitioners. Some providers refer
whenever long-term opioid management begins. Others refer only when
intervention or surgery is needed. When behavior around the use of an
opioid becomes problematic, referral is often prudent. At a minimum,
documentation of the behaviors and an understanding between patient and
provider is necessary. The five As allow the physician to address the issue
and develop a treatment strategy. It is important for the physician to
recognize the risk and recommend a corrective action (i.e., an abnormal
urine drug test may trigger a referral to an addiction medicine provider).
The patient with a substance use disorder may argue and dismiss the risk.

MOTIVATING BEHAVIOR CHANGE IN PATIENTS

WITH CHRONIC PAIN
The key message in managing chronic pain is that the way to improve is
through changes in lifestyle rather than solely through medication or
surgical procedures. This may not always be an easy message for primary
care to deliver because patients may expect their physician to give them
something to cure their problem. Lifestyle and behavior changes are never
easy.
Successful management of chronic pain is much more dependent on
what the patient does than on what the physician does to the patient. The
issue becomes one of the patient’s readiness to accept responsibility and to
adopt a self-management approach. This represents a role reversal for the

5269
physician whose task is not to treat but to understand and motivate patients
for self-management. On occasion, this may include convincing the patient
not to look for another doctor or another procedure.
Because of their unique relationships with patients, primary care
physicians are well suited in motivating patients to change. We are
motivating patients to lose weight, stop smoking, take their medication,
and obtain flu shots. A patient-centered approach, emphasizing the
importance of considering the patient’s perspective when making
treatment recommendations, has been shown to be a valuable technique.42
The goals of a patient-centered approach are to
• Address the patient’s concerns
• Enhance a collaborative relationship
• Provide information that the patient is ready to hear
• Refocus the visit from making treatment recommendations to
supporting the patient’s self-care
• Foster increased patient control of decision making and responsibility
for self-care
This technique requires a reorientation of the traditional patient–
physician relationship. The physician must learn to view the patient as an
autonomous and equal member of the health care team, whose self-
knowledge is pivotal to the management of his or her condition (persistent
pain).
Reflective listening is a technique that involves making statements that
demonstrate the physician’s understanding of what the patient has said.
There are ways of making reflective statements, including the following:
• Restating what the patient has said
• Paraphrasing what the patient has said
• Anticipating and continuing the patient’s thought (i.e., saying what
you believe the patient will say next rather than repeating)
• Reflecting the patient’s feelings
The patient’s readiness to change is the basis of a motivational
approach. According to one well-regarded model,43 patients who strongly
believe that their pain only requires a medical or surgical intervention are
not ready to accept and adopt self-management. On the other hand,
patients who believe that medical and surgical interventions can provide

5270
only limited relief from pain are more likely to perceive benefits from self-
management techniques. Readiness to self-manage should be assessed on a
continuum, and interventions should be tailored to the particular patient’s
level of readiness to change.
The physician can help the patient to understand the importance of
behavior change by guiding him or her through a discussion of the pros
and cons, including whether a given change is attainable, how much effort
it will take, and how much time it will take given the known obstacles.
Motivating the patient involves eliciting the patient’s feelings about and
reasons for pain self-management and reflecting back statements that
support the premise that self-management is possible. Although time-
pressed physicians may balk at the prospect of such a dialogue, the
consultation time is usually more efficient (e.g., fewer arguments, less
resistance) when a patient is encouraged to speak in a focused manner
about a specific problem.

Goals for Pain Self-management

In general, primary care physicians are in agreement about health care
goals such as encouraging smoking cessation, maintaining blood pressure
within normal limits, and controlling blood sugar. Although the goals for
pain self-management are not as clear cut, most pain specialists would
advise primary care physicians to consider the following as important
when motivating a patient:
1. Beginning or maintaining a regular exercise regimen
2. Using medications as prescribed
3. Returning to normal daily activities given the pain condition
4. Practicing appropriate pain and stress-coping strategies (e.g.,
relaxation techniques, reassuring “self-talk”)
5. Returning to or maintaining normal work activities
6. Pacing activities appropriately
7. Monitoring, managing, and/or reporting symptoms of depression as
appropriate
8. Practicing good eating habits (e.g., reducing or maintaining an
appropriate weight)
9. Engaging in other healthy lifestyle behaviors as necessary (e.g.,
reducing alcohol consumption, stopping smoking)

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Importance and Confidence Scales
Patients will change behavior only when they are convinced that it is
important and when they have confidence that the change is possible.
Assessing patient perceptions of importance and confidence can be helpful
when evaluating motivation. For example, patients who give a low rating
to the importance of exercise but a high rating to the belief that exercise
could be done would need help to change their views of the importance of
exercise before adherence could be expected. On the other hand,
brainstorming for solutions may be helpful for those who rate importance
high and confidence low.

Strategies for Helping Patients Understand the Importance of Change

Information and advice presented in a lecturing style often leads to patient
responses of “Yes, but . . .” and the already too brief visit is taken up with
the patient expressing reasons why a recommended change will not work.
Social psychology research has shown that, in general, people are more
likely to believe what they have said over what others have said to them. It
follows that a didactic approach may undermine the physician’s attempts
to motivate the patient.
Primary care providers are invested in behavior change and motivation.
Four strategies have been shown to be effective in helping patients
understand the importance of change and increase their confidence to
make that change.44 These uncomplicated strategies are effective because
they enable patients to talk themselves into using pain self-management
techniques.
1. Always elicit positive statements from the patient. Use the “why so
high” technique. For example, ask the patient with chronic pain to
rate the importance of daily exercise on a scale of 0 (low) to 10
(high). If the patient’s answer is 5, ask “Why so high? Why not a 1?”
Most patients understand the importance of conditioning and
exercise in pain rehabilitation. By asking “why so high,” the patient
provides the evidence for an exercise program. Once you know the
patient’s thought process, you can use this to motive a change of
behavior.
“You think it is very important for you to make your muscles stronger
to make your pain better” (restating what the patient has expressed).

5272
2. Examine the pros and cons of behavior change. Patients will feel
ambivalent about self-management. This allows the patient to
explore feelings and think through self-management in a judgment-
free environment. Bear in mind that although this technique is easy
to understand, it can be difficult for the physician to do. He or she
must listen, encourage, and provide a summary at the end of the visit.
“What do you think will happen if you continue to stay in bed?” The
patient may steer the conversation back to you: “Unless you make me
better, I cannot get out of bed” or “Unless you give me more pain
medication, I will not be able to get out of bed.” Be persistent and
keep to the same question. The patient has stated earlier that
conditioning and exercise are important.
“Your mother was sick all the time. How did that affect you?”
Patients may have an environmental background for pain in another
family member which impacted them when growing up. Patients may
also express concern about the impact of their pain on the other
members of the family. The desire to have their pain not have an
impact may motivate the patient to different behavior.
3. Elicit patient concerns about the status quo. Patients who rate the
importance of pain self-management as low may be concerned about
their current situation. Ask the patient to talk about the consequences
of not making the behavior change. Once the patient has listed as
many concerns as he or she can think of, summarize these, using the
patient’s words if possible. This may help to increase the patient’s
perception of the importance of the change.
“If things do not change, what will happen?” The patient may try to
guide the discussion back to you and the medical profession,
disability, or legal issues. Be persistent about “What will happen with
your spouse or children; how will you pay the bills?”
4. Brainstorm for solutions. Without giving specific advice, remind the
patient that there are usually many ways to achieve self-management.
Guide the patient in conceptualizing a number of possibilities. Help
the patient to decide which possibilities might work best for him or
her. Guide the patient to develop plan for achieving his or her goal.
“You spend 16 hours of your day in bed. Any activity makes your

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 pain worse. The last time you tried to exercise, your pain was at a
9/10 and you wanted to go to the hospital. How are you going to get
to exercise?” Keep the focus on what the patient can do, or what
solutions the patient has. Add suggestions and advice related to the
patient’s solutions.
Once the patient has adopted a self-management plan with specific
goals, the physician can use open-ended questions to encourage the patient
to talk about his or her progress. The questions should communicate the
physician’s interest in the patient’s perspective. For instance, “At your last
visit, you were thinking about making some changes in pacing your work.
I’d be interested in hearing how this is going and whether you’ve noticed
any change in your ability to manage your pain.” Such questions enable
the physician to conduct an informal assessment of the patient’s readiness
and also enhance rapport with the patient.

Emerging Models of Care

There is increasing recognition that team-based care, where providers from
multiple disciplines collaborate in the care of patients with chronic pain,
may be the key to optimizing primary care’s foundational role in chronic
pain management.45 Collaborative care models, adopting successful
approaches from other conditions like depression and diabetes, have
demonstrated promise in integrated health systems for treatment of chronic
pain. These successful programs, published as clinical trials, usually
feature a care manager, such as a pharmacist, nurse, or advanced practice
nurse, who collaborates with a physician to provide referral-based care to a
population of patients embedded within group practices. Several recent
studies have demonstrated success with these models in terms of pain
intensity, pain-related functional interference, use of multimodal pain care,
and patient satisfaction.46–49 Cost-effectiveness studies and
implementation trials—to address issues of more widespread
dissemination of these models—are underway. Another example of team-
based care involved a study where nurses team with primary care
providers in an intervention that improved adherence with opioid therapy
for chronic pain guidelines.50 More resource-intensive primary care–based
clinics that manage patients with high-risk opioid use and chronic pain

5274
have also demonstrated initial promise.51

Conclusion
Persistent pain, a highly prevalent condition in the United States, has a
significant impact on our health and productivity as a society as well as on
our medical and financial resources. Primary care is the most appropriate
setting for the management of patients with chronic pain because of the
mutual understanding that results from a long-standing physician–patient
relationship. The barriers to managing chronic pain are significant but not
insurmountable. Persistent pain is similar to other chronic illness but also
has many unique differences, making management complicated and
difficult in the busy primary care office. A new skill set is required by the
provider to help the undertreatment of pain. Available tools (e.g.,
questionnaires, pain diaries, pain scales) and techniques (e.g., reflective
listening, goal setting) make it possible for the primary care physician to
provide management for patients with chronic pain in a 15-minute office
visit. Diabetes, chronic obstructive pulmonary disease, and other chronic,
complicated illnesses require other skills yet have been handled skillfully
and competently in the primary care setting.
Some of the most appreciative patients are those who have a
sympathetic provider to help them with chronic pain. Yet treating chronic
pain patients is rarely met with enthusiasm in primary care. Patients with
chronic pain may have complex conditions that are rarely cured. They may
have previously made little progress toward normal life functioning and
often have complex psychosocial issues that a physician cannot address.
There is never sufficient time to adequately follow up patients with pain.
The primary care provider is accustomed to dealing with chronic problems
through short, focused visits and a longitudinal experience. A treatment
plan and mutually agreed on goals allow the physician to conduct a follow-
up visit in 15 minutes by focusing discussions on the treatment success
that both the physician and patient desire.

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mind and the spine—which goes first? Spine (Phila Pa 1976) 1993;18(1):66–71.
33. Fishbain DA, Cutler R, Rosomoff HL, et al. Chronic pain-associated depression: antecedent or
consequence of chronic pain? A review. Clin J Pain 1997;13(2):116–137.
34. Jacox AK, Carr DB, Capman CR, et al. Acute pain management: operative or medical
procedures and trauma. Clinical Practice Guideline No. 1; 1992. AHCPR publication no. 92-
0032.
35. White KP, Nielson WR, Harth M, et al. Does the label “fibromyalgia” after health status,
function, and health service utilization? A prospective, within-group comparison in a
community cohort of adults with chronic widespread pain. Arthritis Rheum 2002;47(3):260–
265.
36. Butler SF, Budman SH, Fernandez K, et al. Validation of a screener and opioid assessment
measure for patient with chronic pain. Pain 2004;112:65–75.
37. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treatment patients:
preliminary validation of the Opioid Risk Tool. Pain Med 2005;6:432–442.
38. Skinner HA. The drug abuse screening test. Addict Behav 1982;7(4):363–371.
39. Clark JD. Chronic pain prevalence and analgesic prescribing in a general medical population.
J Pain Symptom Manage 2002;23:131–137.
40. Oster G, Berger A, Dukes E, et al. Use of potentially inappropriate painrelated medications in
older adults with painful neuropathic disorders. Am J Geriatr Pharmacother 2004;2(3):163–
170.
41. Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the
use of opioids. Adv Ther 2000;17:70–83.
42. Stewart MA, McWhinney IR, Weston WW, et al. Patient-Centered Medicine: Transforming
the Clinical Method. Thousand Oaks, CA: Sage Publications; 1995.
43. Prochaska JO, DiClemente CC, Norcoss JC. In search of how people change. Applications to
addictive behaviors. Am Psychol 1992;47:1102–1114.
44. Rollnick S, Mason P, Butler C. Health Behavior Change: A Guide for Practitioners.
Edinburgh: Harcourt Publisher; 1999.
45. Seal K, Becker W, Tighe J, et al. Managing chronic pain in primary care: it really does take a

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 village. J Gen Intern Med 2017;32(8):931–934.
46. Bair MJ, Ang D, Wu J, et al. Evaluation of stepped care for chronic pain (ESCAPE) in
veterans of the Iraq and Afghanistan conflicts: a randomized clinical trial. JAMA Intern Med
2015;175(5):682–689.
47. Kroenke K, Krebs EE, Wu J, et al. Telecare collaborative management of chronic pain in
primary care: a randomized clinical trial. JAMA 2014;312(3):240–248.
48. Kroenke K, Bair MJ, Damush TM, et al. Optimized antidepressant therapy and pain self-
management in primary care patients with depression and musculoskeletal pain: a randomized
controlled trial. JAMA 2009;301(20):2099–2110.
49. Dobscha SK, Corson K, Perrin NA, et al. Collaborative care for chronic pain in primary care:
a cluster randomized trial. JAMA 2009;301(12):1242–1252.
50. Liebschutz JM, Xuan Z, Shanahan CW, et al. Improving adherence to long-term opioid
therapy guidelines to reduce opioid misuse in primary care: a cluster-randomized clinical trial.
JAMA Intern Med 2017;177(9):1265–1272.
51. Becker WC, Edmond SN, Cervone DJ, et al. Evaluation of an integrated, multidisciplinary
program to address unsafe use of opioids prescribed for pain [published online ahead of print
March 23, 2017]. Pain Med. doi:10.1093/pm/pnx041.

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CHAPTER 109
Pain Management at the End of
Life
JUDITH A. PAICE

Adequate relief of pain at the end of life is an ethical imperative. Studies

suggest that although pain may not be the most prevalent symptom during
the final days or weeks of life, it is frequently the most distressing.1–7 In
addition to the negative consequences pain has on the patient, inadequate
pain control adversely affects the ongoing emotional well-being of family
and friends at the bedside. To witness unrelieved pain during the final
hours of life leaves long-lasting negative memories of the dying process
that can hamper bereavement. The setting of care can dictate whether
patients will receive adequate relief during the dying process, and
significant change in our systems of care is needed. The majority of end-
of-life care is currently provided in institutions, with more than two-thirds
of individuals dying in hospitals or nursing homes. In a large survey of
surviving family members, more than 25% reported that their loved one
received inadequate relief of pain in these settings.8 The challenge for our
health care system is to ensure that regardless of setting, pain management
at end of life is provided by skilled professionals who understand the
special needs of the dying. These skills include assessment of pain in those
who might not be able to verbally describe their pain, awareness of pain
syndromes common at end of life, as well as familiarity with the
pharmacologic and nonpharmacologic management of pain in the dying.
Furthermore, clinicians must be aware of the role of suffering and
existential distress as well as management of intractable symptoms.

Introduction
Currently, death in developed countries is more likely to occur after a long

5279
chronic illness. This is in contrast to a century ago when people died a
more rapid death, often due to infection. Currently, the most common
causes of death in high-income countries include ischemic cardiac disease,
cerebrovascular disease, and cancer.9 Globally, more than 70% of deaths
are due to chronic, noncommunicable diseases, principally cardiovascular
diseases and diabetes, cancers, and chronic respiratory diseases.9 Thus,
people are more likely to die after a long, protracted illness, and pain is a
common comorbidity of these illnesses. Several care delivery models exist
to address the specialized pain and symptom needs of those with life-
threatening illnesses, including palliative care and hospice. Both of these
care models focus attention on the patient and family, not unlike the
structure of care delivered in truly interdisciplinary pain treatment
programs.

PALLIATIVE CARE
Palliative care strives to relieve suffering and improve the quality of life of
those individuals with a life-threatening illness.10 The palliative care
movement in the United States originated in academic medical centers but
has moved into community hospitals, outpatient clinics, and other centers
of care. Palliative care programs are rapidly growing within hospitals,
existing in 67% of hospitals in the United States with 50 or more beds and
in 90% of hospitals with 300 or more beds.11 Commitment to early
identification, thorough assessment, and effective treatment of pain are key
components of palliative care, as is attention to other physical,
psychosocial, and spiritual concerns.12 The goal is to neither hasten nor
prolong death but rather affirm life by offering a support system to patients
and families. To that end, palliative care is optimally provided by an
interdisciplinary group of professionals, including physicians, nurses,
social workers, chaplains, and others.
Confusion persists regarding the timing of appropriate referral to
palliative care. Previous models of care incorporated palliative care during
the final phases of life, once all curative therapy was completed (Fig.
109.1). It is clear that patients and families benefit greatly when palliative
care is integrated into the plan of care early during the course of illness
(Fig. 109.2). Effective pain management provided during cancer treatment,

5280
for example, can allow patients to complete potentially curative or life-
prolonging therapies.13 Attention to other symptoms associated with the
underlying illness, including distressing complications of treatment, can
provide improved quality of life during this time. Research supports the
feasibility and benefit of integrating palliative and oncology care in
ambulatory patients.14–19

FIGURE 109.1 Previous models of palliative care and hospice.

FIGURE 109.2 Proposed model for integration of palliative care.193

HOSPICE
The modern concept of hospice care developed from the work of Dame
Cicely Saunders and others in the United Kingdom during the 1960s. In
this model, freestanding centers of care were developed where patients
spent their final days receiving pain and symptom management, along with
attention to the emotional and spiritual aspects of the individual’s life. A
decade later, hospice began in the United States with the same goals of

5281
care, but a home-based model quickly took root. In 1982, the Medicare
Hospice Benefit was passed to provide reimbursement for these services.
A Medicare Part A beneficiary is eligible for this benefit if she or he is
determined to have a life expectancy of 6 months or less if the life-limiting
disease or combination of comorbid conditions runs its normal course.20
Studies reveal that patients at end of life and their family members prefer
care provided in the home with the support of hospice, reporting improved
symptom management and significantly greater satisfaction with the
overall quality of care.8,21 Both of these models, palliative care and
hospice, provide support to patients and loved ones. As pain is so
prevalent, all health care professionals working with people at this time of
life must be exceptionally knowledgeable about common pain syndromes
as well as appropriate assessment and management.

Pain Syndromes Common at the End of Life

Pain syndromes specific to cancer have been well characterized; yet, much
research is needed to describe pain associated with other life-threatening
illnesses. Furthermore, greater attention is needed to identify pain
syndromes most common at the very end of life along with appropriate
treatment strategies (Table 109.1).

TABLE 109.1 Pain Syndromes in Palliative Care194–196

Pain Related to Underlying Disease
Tumor-related pain due to pressure or compression
Chest pain due to end-stage cardiac disease
Ischemia caused by atherosclerotic disease
Abdominal pain with referral to thorax and shoulder due to liver failure, cirrhosis
Abdominal pain due to ascites
Extremity skin pain due to edema
Back pain and skin discomfort/pruritus due to end-stage renal disease
Chest pain due to pulmonary fibrosis, emphysema, other advanced lung disorders
Central nervous system infection (meningitis, cryptosporidium) leading to headache
Central pain after stroke, particularly affecting thalamus
Trigeminal neuralgia in multiple sclerosis
Vaso-occlusion leading to bone, muscle, and visceral pain in sickle cell disease
Rapid onset of cachexia leading to peripheral neuropathy
Spasticity due to neuromuscular disorders
Pain Related to Treatment

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 Peripheral neuropathy due to cancer chemotherapy or treatment of HIV/AIDS
Arthralgias and myalgias due to aromatase inhibitors
Surgically induced phantom pain, chronic neuropathy
Immunocompromise leading to postherpetic neuropathy
Radiation-induced plexopathies, osteoradionecrosis, lymphedema
Graft-versus-host disease after stem cell transplant leading to skin and mucous membrane
lesions
Aseptic necrosis due to prolonged corticosteroid use
Pain Unrelated to Disease or its Treatment
Pressure ulcers
Reduced muscle and fat padding at bony prominences
Muscle atrophy leading to myalgia
Immobility leading to joint pain
Contractures
Adapted from Von Roenn JH, Paice JA, Preodor ME. Pain management in palli-ative care. In: Von
Roenn JH, Paice JA, Preodor ME. Current Diagnosis & Treatment of Pain. 1st ed. New York:
Lange; 2006.

CANCER
Prevalence rates of pain in advanced cancer vary based on the settings of
care in which the studies were conducted, the instruments used to measure
pain and other symptoms as well as the methods employed in data
collection. In general, approximately two-thirds of patients with advanced
malignant disease experience pain.22–25 Cancer patients referred to
palliative care or hospice commonly have a greater prevalence of pain and
other symptoms. Regarding the pain trajectory in cancer patients very near
the end of life, pain occurred in 54% and 34% at 4 weeks and 1 week prior
to death, respectively.26 Children dying of cancer also are at risk for pain
and suffering.27,28 The result of unrelieved pain and associated
interference may include increased desire for hastened death.29,30

NONCANCER DIAGNOSES
Many life-threatening illnesses are known to cause pain, including human
immunodeficiency virus,31 multiple sclerosis,32–35 amyotrophic lateral
sclerosis,36 other neurologic disorders,37 end-stage renal disease,38 and
heart failure.39,40 At the end of life, it is apparent that many of the
preexisting pain syndromes associated with these disorders can escalate,
particularly pain related to progression of disease, immobility, or comorbid
complications. Furthermore, many patients with advanced disease are

5283
elderly and more likely to have existing chronic pain syndromes, such as
osteoarthritis or low back pain.41 Regrettably, there have been few studies
characterizing the prevalence of pain or the types of pain experienced by
these individuals with noncancer diagnoses. Greater awareness of the risk
and types of pain seen will lead to improved detection, assessment, and
treatment.

Pain Assessment at the End of Life

CHALLENGES IN PAIN ASSESSMENT
Comprehensive assessment of pain at the end of life is imperative. As with
all pain, assessment must be conducted upon initial presentation, regularly
throughout the course of care, and during any changes in the patient’s pain
state.42 Documentation of and communication about these findings are
crucial. Assessment in patients who are cognitively intact and able to
verbalize can incorporate standard intensity tools such as the numeric
rating scale (NRS), the verbal descriptor scale (VDS), the visual analogue
scale (VAS), or the Brief Pain Inventory (BPI) for more comprehensive
evaluation.43 A panel of international experts in palliative care rated
essential components of pain assessment to include intensity, temporal
pattern, treatment and exacerbating/relieving factors, location, and
interference with health-related quality of life as essential dimensions.44 In
their content evaluation of more than 64 pain assessment tools, none were
found to satisfactorily incorporate all of these domains.
Tools exist that measure multiple symptoms seen in lifethreatening
illness, and the majority include pain. One study demonstrated that using
systematic assessment of symptoms in palliative care yielded a 10-fold
greater number than when volunteered by the patient. The investigators
conclude that specific detailed symptom investigation is necessary.45
Examples of tools include the Edmonton Symptom Assessment Scale,46
the M.D. Anderson Symptom Inventory,47 the Memorial Symptom
Assessment Scale,48–50 the Rotterdam Symptom Checklist,51,52 the
Symptom Distress Scale,53 and others. One constraint of these scales for
clinical care at end of life is the length of most of these tools, leading to
respondent fatigue. The Brief Hospice Inventory54 was developed

5284
specifically to evaluate symptoms, including pain, and satisfaction with
hospice care. Initial testing revealed that patients at end of life could
complete the instrument.
A wide range of health-related quality-of-life instruments, such as the
European Organisation for Research and Treatment of Cancer QLQ-C30
and the Functional Assessment of Cancer Therapy—General, include
symptoms such as pain, but the burden to complete these tools preclude
their use in those with advanced disease. Several tools target patients at the
end of life: the Hospice Quality of Life Index,55,56 the McGill Quality of
Life Questionnaire, and others.57 These instruments include symptoms and
can be useful in assessing the global needs of dying patients. Although
these tools are appropriate for patients who are cognitively intact, many
patients at the end of life develop delirium, some have dementia, and
others have limited ability to communicate due to intubation or neurologic
disorders.

PAIN ASSESSMENT IN THE COGNITIVELY IMPAIRED

Several excellent reviews thoroughly describe tools used to assess pain in
cognitively impaired older adults, primarily those with dementia (Table
109.2).58–60 Although many of these tools may be adapted to assess pain in
the dying person with delirium or other disorders, none have undergone
extensive testing in these populations.

TABLE 109.2 Pain Assessment Tools in Nonverbal Patients that

May Be Useful in End-of-Life Care
Dementia
Assessment of Discomfort in Dementia Protocol
Checklist of Nonverbal Pain Indicators
Nursing Assistant-Administered Instrument to Assess Pain in Demented Individuals
Pain Assessment Scale for Seniors with Severe Dementia
Pain Assessment in Advanced Dementia Scale
Intubated or Unconscious Children (Neonates, Infants, Nonverbal Children)
COMFORT Behavior Scale
Distress Scale for Ventilated Newborn Infants
Faces, Legs, Activity, Cry, Consolability Observational Tool
Intubated or Unconscious Adults
Behavioral Pain Scale
Critical-Care Pain Observation Tool

5285
PAIN ASSESSMENT IN THOSE UNABLE TO
COMMUNICATE
One in five people who die in hospitals have used intensive care unit
(ICU) services during their final hospitalization.61,62 In a large multicenter
study of patients with serious illness, half of those who died during
hospitalization had received ICU care.63 Thus, significant percentages of
people with life-threatening illness will be admitted to the ICU prior to
death. Yet, one in five patients in ICU lack decision-making capacity and
are likely unable to accurately describe their pain.64 Furthermore, although
a number of these patients may be cognitively intact, the use of mechanical
ventilation often complicates pain assessment. Some patients may be able
to use an NRS, VDS, or VAS, either by pointing to a chart with numbers
or a line representing pain or by nodding “yes” when asked sequentially if
pain is “mild,” “moderate,” or “severe.” For those patients who cannot use
these techniques, several pain assessment tools have been developed to
assess pain in the ICU, including the Behavioral Pain Scale 65 and the
Critical-Care Pain Observation Tool.66,67 For children, several tools exist,
including the Faces, Legs, Activity, Cry, Consolability Observational Tool
(validated in children 2 months to 7 years and tested in the ICU),68
Distress Scale for Ventilated Newborn Infants (tested in ventilated
newborns), and the COMFORT Behavior Scale (tested in neonates to 3
years of age in ICU).69
Although standardized instruments to measure pain at the end of life are
needed, several principles can guide clinicians when patients are
cognitively impaired and unable to report pain.58 Behaviors suggestive of
pain should be evaluated, including the furrowed brow, guarding, or
vocalizing on movement. Consider causes of pain, including the
underlying disease and treatments, as well as new complications such as
pressure ulcers, constipation, urinary retention, or infection. Ask family
members or others who have known the patient if they observe changes in
behaviors that might imply discomfort. If any of these indicators suggest
that the patient may be in pain, initiate an analgesic trial and reassess.
Resolution of the behaviors provides suggestive evidence that pain exists.
Regular administration of the analgesic should then be included in the
treatment plan.

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PAIN MEASUREMENT IN RESEARCH CONDUCTED
AT END OF LIFE
Research in pain at the end of life is hampered by lack of consistency in
the use of valid and reliable pain measurement tools. An expert working
group convened by the European Association of Palliative Care
recommended standardized methods be applied in clinical trials and other
pain studies in those with life-threatening illnesses. They recommended
unidimensional tools such as the NRS, VAS or verbal rating scales, or,
when indicated, multidimensional tools such as the BPI-Short Form or the
McGill Pain Questionnaire.70

Pain Management Strategies at End of Life

The principles employed in treating other patients in pain should be
applied to the dying. These include the use of multimodal therapies based
on the underlying pain mechanisms as determined by comprehensive
assessment. Of particular challenge at the end of life is the need for
alternate routes of administration and a plan of care when pain becomes
intractable to standard therapies or adverse effects to the treatment become
unmanageable.

ROUTES OF DRUG DELIVERY

Many patients can use the oral route until death. In one study, 43% and
20% of cancer patients were able to take oral opioids at 1 week and 24
hours before death, respectively.26 When oral delivery is no longer
feasible, alternate routes of administration are available. Oral routes,
including sublingual, transmucosal, and buccal delivery, as well as enteral,
rectal, nasal, parenteral, spinal, topical, and transdermal routes, have all
been employed.

Oral, Sublingual, Transmucosal, and Buccal Routes

When patients have difficulty swallowing pills but can take soft food,
microsphere formulations of long-acting morphine or oxycodone provide
sustained release when the capsule is broken open and the “sprinkles” are
placed in applesauce or other soft food. Oral opioid solutions (e.g.,

5287
morphine, oxycodone, hydromorphone, or methadone) can be swallowed
or small volumes (0.5 to 1 mL) of a concentrated solution can be placed
sublingually or buccally in patients whose swallowing abilities are limited.
Nevertheless, buccal and sublingual uptake of these opioids is slow and
not very predictable, particularly with more hydrophilic compounds such
as morphine.71,72 Small studies suggest that most of the analgesic effect of
morphine administered in this manner is due to drug dripping down the
oropharynx and into the gastrointestinal tract.73 Conversely, absorption
with the use of more lipophilic drugs, such as methadone and fentanyl, is
relatively high.72 Immediate-release fentanyl products will be described in
the following text. Topical morphine and methadone mouthwashes have
been reported to treat chemotherapy-induced oral mucositis and might be
useful for other pain syndromes associated with oral lesions.74–76

Transmucosal Immediate-Release Fentanyl Products

Immediate-release fentanyl products are available as lozenges, sublingual
tablets and sprays, and buccal tablets and film as well as nasal delivery.77
The lipid solubility of fentanyl allows more rapid onset when compared
with hydrophilic compounds, making these products useful for
breakthrough pain. All of these products are approved for patients who are
already tolerant to opioids, and in general, the dose of the long-acting
opioid does not predict the effective dose of the transmucosal agent. One
major obstacle to the use of these products is their cost, limiting use in
hospice or other capitated healthcare delivery systems.
In the United States, the U.S. Food and Drug Administration has
instituted a Risk Evaluation and Mitigation Strategy (REMS) for
transmucosal immediate-release fentanyl (TIRF) products. This program
requires prescribers to enroll in the TIRF REMS Access Program after
reading educational materials and completing a test knowledge focusing
on safe use of these products.78 This program applies to transmucosal
(buccal and sublingual) and nasal fentanyl products.
Oral transmucosal, sublingual, and buccal fentanyl: Oral
transmucosal fentanyl citrate (OTFC) is a lipid-soluble (lipophilic)
synthetic opioid formulation that consists of a lozenge on a stick. Patients
must actively rub the fentanyl-containing lozenge against the oral mucosa

5288
to provide rapid absorption of the drug, usually experiencing some relief in
5 to 15 minutes, with a peak effect of 30 minutes.77,79,80 Too rapid
application, usually less than 15 minutes, will result in more of the agent
being swallowed rather than being absorbed transmucosally. Some patients
develop oral candida due to the high sugar content of the compound, and
others complain of the sweet taste and lack of variety in flavor, particularly
with prolonged use. Xerostomia can reduce bioavailability of the agent and
altered dexterity may complicate use.
Other transmucosal fentanyl products include fentanyl sublingual tablet
(FST)81 and fentanyl sublingual spray (FSS)82 as well as fentanyl buccal
tablet (FBT)83 and fentanyl buccal soluble film (FBSF).84
These products are generally well tolerated and produce more rapid
onset of analgesia when compared with immediate-release oral morphine.
A randomized study compared FSTs with subcutaneous morphine in
people with severe cancer breakthrough pain and found that more than
90% of patients preferred the tablets.81 Few trials compare these fentanyl
products for superiority. In one study, the rate and extent of fentanyl
absorption were greater following FBT compared to OTFC, such that
approximately 30% less drug was required when administering FBT to
achieve similar OTFC systemic drug levels.80
Nasal fentanyl: Two nasal fentanyl preparations are accessible globally
for breakthrough pain, intranasal fentanyl spray (INFS) and fentanyl pectin
nasal spray (FPNS), although in the United States, only FPNS is available.
Both of these delivery systems provide significant analgesia within 10
minutes.85,86

Enteral and Rectal

Preexisting enteral feeding tubes can be used to deliver medications when
patients cannot swallow at the end of life. It is rare that circumstances
would require placement of a tube at this time, and doing so may send a
contradictory message about the need for enteral nutrition and hydration.
The size of the tube and volume of fluid used to mix the “sprinkles”
formulation of morphine or oxycodone must be considered when
delivering this form of long-acting opioid to avoid obstruction of the
tube.87

5289
 Opioids can be delivered via the rectal route using commercially
prepared suppositories, compounded suppositories, or microenemas.
Studies suggest a larger area under the curve when morphine suppositories
are used when compared with oral sustained-release morphine.88
Sustained-release morphine tablets have also been used rectally, with
resultant delayed time to peak plasma level and approximately 90% of the
bioavailability achieved by oral administration.89 Rectal methadone can be
used safely and has bioavailability approximately equal to oral
methadone.90,91 Neutropenia and thrombocytopenia are generally
considered contraindications to rectal drug administration, but clinicians
must consider the goals of care for delivering these drugs as well as the
risks and benefits at this time of life. Painful rectal lesions, such as
hemorrhoids or fissures, preclude the use of these routes. Attempting to
place agents rectally at home may be difficult for family members when
caring for loved ones who cannot move or reposition without significant
assistance.

Parenteral
Parenteral administration includes intravenous and subcutaneous delivery
of drug. Intramuscular opioid delivery is inappropriate in the palliative
care setting due to the pain associated with this route and the variability in
systemic uptake of the drug.42 Intravenous administration of drugs is often
used when patients are hospitalized at end of life, as this route provides
rapid and predictable drug delivery. For patients being cared for at home,
the need for vascular access may be cumbersome. Subcutaneous infusions,
including morphine, hydromorphone, and fentanyl, provide an effective
and safe alternative.92 Methadone has been reported to cause local site
irritation, although small case reports suggest that lower doses given
intermittently are less likely to cause pain.93 Subcutaneous boluses of
morphine have a slower onset and lower peak effect when compared with
intravenous boluses, although with continuous infusions they provide
similar blood levels and resultant pain relief.94 Subcutaneous infusions
may include up to 10 mL per hour, although most patients absorb 2 to 3
mL per hour with the least difficulty. Volumes greater than 10 mL per
hour are often poorly absorbed and can lead to pain or leakage of fluid.

5290
Hyaluronidase has been reported to speed absorption of subcutaneously
administered fluids, although a randomized trial yielded no difference in
pain or edema between treatment and placebo groups.95 Despite these
findings, these investigators and others suggest that hyaluronidase may
have utility when subcutaneous absorption is not well tolerated.

Spinal (Epidural/Intrathecal)
Intraspinal routes, including epidural or intrathecal delivery, allow
administration of drugs such as opioids, local anesthetics, and/or α-
adrenergic agonists more proximate to their respective effector sites.96,97 A
randomized controlled trial demonstrated benefit for ambulatory cancer
patients with a life expectancy of at least 3 to 6 months experiencing
pain.98 However, initiating this therapy during the final hours of life
requires the availability of experts to place an external catheter as well as
caregivers with specialized knowledge to safely and effectively provide
care. As with all therapies, the potential risks, including greater caregiver
burden, need to be weighed against the benefits. Intraspinal delivery may
be considered when patients do not obtain adequate relief from aggressive
titration of systemic opioids and other analgesics or they experience
intolerable adverse effects. A systematic review of spinal opioids in cancer
pain found only weak evidence to recommend this therapy.99 More
information regarding the use of intraspinal drug delivery is available in
Chapter 100.

Topical
Topical morphine administration to open areas, such as pressure ulcers,
burns, malignant skin lesions, and ulcers associated with venous stasis or
sickle cell disease, has been reported to be effective in case reports and
open-label trials.100–102 However, a randomized controlled trial of topical
morphine used to treat painful skin ulcers found no benefit when compared
with placebo.103 An analysis of the bioavailability of morphine when
delivered to open ulcers found little systemic uptake, a possible
explanation for the lack of efficacy.104 Topical morphine applied to the
wrist in a pluronic lecithin organogel (PLO) base for systemic delivery is
being used in some settings; yet, evidence of its efficacy is lacking. A

5291
bioavailability study of topical morphine in healthy volunteers revealed
that morphine was seldom detected in plasma samples after topical
administration, and when values were detected, they were below the level
of quantification.105 These results suggest that topical administration of
morphine compounded in a PLO base for topical drug delivery is unlikely
to provide relief of pain.

Transdermal
Transdermal fentanyl has been used extensively, and a wide range of
dosing options (ranging from 12- to 100-μg-per-hour patches) makes this
route particularly useful in cancer pain and palliative care.106 Most
individuals experience relief for 3 days, although approximately 25% of
patients will consistently report increased pain on the third day, despite
adequate use of breakthrough medications. These patients benefit from
changing the patch more frequently (every 48 hours). Equianalgesic dosing
with other opioids has been unknown; a recent study suggests that a 100-
μg patch is approximately equivalent to 240 mg of oral morphine
equivalents.107 Fentanyl is another option when considering opioid
rotation, and several reports suggest the resolution of delirium when
patients are converted from other opioids to transdermal or intravenous
fentanyl.108,109 Fever, diaphoresis, cachexia, morbid obesity, and ascites
may have a significant impact on the absorption, predictability of blood
levels, and clinical effects of transdermal fentanyl, although studies are
lacking. There is some suggestion in open-label and retrospective studies
that transdermal fentanyl may produce less constipation than long-acting
morphine.106,110 A small subset of patients will develop skin irritation due
to the adhesive in any patch. Because most topical antihistamines consist
of an oil base which would prevent patch adherence, the use of an aqueous
based steroid inhaler (intended for the management of asthma) applied
prior to patch administration can preclude skin reactions and allows the
patch to remain in place.

INTRACTABLE PAIN OR UNMANAGEABLE ADVERSE

EFFECTS OF TREATMENT
Although most pain at end of life can be well managed with available

5292
therapies, intractable pain or unmanageable adverse effects can occur that
can lead to incredible suffering. In some cases, pain escalates due to
rapidly increasing disease burden. At other times, pharmacokinetics of the
opioids and other analgesics are altered by organ dysfunction associated
with the dying process, leading to inadequate relief.

Effect of Organ Dysfunction on Pharmacokinetics

Organ dysfunction at the end of life will alter the absorption, distribution,
metabolism, and elimination of analgesic agents, thereby influencing the
efficacy of the drug. People with advanced malignancy or other life-
threatening illness may undergo changes in any of these phases as a result
of extensive disease. Little is known about the alterations in absorption of
opioids that occur when people are dying. Factors such as shortened
gastrointestinal transit time may delay absorption of oral opioids,
particularly long-acting or sustained-release compounds.
Distribution of the drug is in part dependent on plasma proteins within
the vasculature, body fat stories, and total body water. These can all be
significantly altered in patients who are cachectic and dehydrated at the
end of life. Aging patients are known to have decreased volume of
distribution of morphine and fentanyl. Additionally, methadone binds
avidly to α1 glycoprotein, which is increased in advanced cancer. This
leads to decreasing amounts of unbound methadone and a delayed onset of
analgesic effect.
Metabolism of drugs can be changed by advanced age, liver
dysfunction, and other factors that are widespread in palliative care.111
Excretion can be altered as renal failure occurs, particularly because most
opioids, with the exception being methadone, are primarily excreted by the
kidneys. Patients with renal failure or those receiving dialysis might
benefit from the use of agents that are more readily dialyzable, such as
fentanyl, as opposed to morphine or codeine.110,112 Research is needed
regarding the effect of advanced disease and the dying process on the
pharmacokinetics of analgesics, particularly opioids.

Myoclonus
One consequence of altered pharmacokinetics at the end of life is the

5293
development of myoclonus. Myoclonus is a sudden, uncontrollable,
nonrhythmic jerking of the extremities. This can be extremely distressing,
causing fatigue and sleep disruption and exacerbating the patient’s pain.
Furthermore, myoclonus can progress to the development of uncontrolled
seizures.113 Myoclonus has been reported to occur after surgery to the
brain,114 in acquired immunodeficiency syndrome,115 after hypoxia,116 and
after chlorambucil administration.117 However, myoclonus at end-of-life
care is most commonly associated with opioids. Controversy exists
regarding whether this is dose dependent and how much of this effect is
from parent drug versus metabolites. Most reports of opioid-related
myoclonus implicate higher doses, although it has been reported to occur
in patients receiving low doses of opioids, particularly
hydromorphone.118,119 Other opioids that have been implicated include
methadone120 and fentanyl.121 Myoclonus has also been reported during
withdrawal from transdermal fentanyl.122,123
The underlying mechanism of opioid-induced myoclonus is poorly
understood. Myoclonus and seizures have been reported to occur in
patients receiving high-dose morphine or hydromorphone
administration.124 However, Fainsinger and colleagues125 describe a case
of myoclonus occurring with stable hydromorphone dosing in the face of
acute renal failure. A retrospective chart review found that in terminally ill
patients receiving parenteral hydromorphone, the dose and duration of
drug were associated with the development of myoclonus, whereas age,
gender, and diagnosis were not.126 These findings point to the role of
accumulating neuroexcitatory metabolites that are poorly excreted either
due to prolonged dosing, high doses, or concomitant renal failure. The 3-
glucuronide metabolites are implicated as contributing to these
neuroexcitatory effects.127 Both morphine-3-glucuronide (M3G) and
hydromorphone-3-glucuronide (H3G) are believed to produce excitatory
behaviors, including myoclonus, allodynia, and seizures. In a study of
cancer patients who developed allodynia and myoclonus during morphine
infusions, M3G levels were elevated.124 Case reports suggest that M3G
and H3G plasma levels are greatly increased in the presence of renal
failure, with the ratio of metabolite to parent compound four times higher
than the ratio seen in patients with normal renal function.128,129 However,

5294
one prospective study found no relationship between myoclonus and renal
function.130 In rodent models, H3G has more potent neuroexcitatory
effects when compared with M3G.131 However, a pilot study of people in
hospice receiving morphine and experiencing myoclonus revealed no
elevation in M3G levels.132
Regardless of the underlying cause, treatment is imperative. The goal is
to significantly reduce the dose of the opioid, and this is usually
accomplished by rotation to an alternate opioid.133,134 Methadone has been
used as an alternative agent with success, although other opioids may be
easier to titrate and methadone also has been found to produce
myoclonus.120 Other strategies include adding adjuvant analgesics and
using interventional techniques (e.g., spinal drug administration, nerve
blocks) to potentially reduce the amount of total systemic opioid.
Ketamine has been suggested as beneficial to rapidly reduce systemic
opioid dose.135 Little research is available regarding agents used to reduce
myoclonic jerking. Benzodiazepines, including clonazepam, diazepam,
and midazolam, have been recommended.133,136 The mechanism of action
of benzodiazepines is through binding to γ-aminobutyric acid type A
(GABAA) receptors within the central nervous system, leading to central
nervous system depression. At higher doses, benzodiazepines may also
limit repetitive neuronal firing, similar to several anticonvulsant
compounds. Clonazepam may be useful in patients who can swallow, with
doses starting at 0.5 to 1 mg by mouth every 6 or 8 hours, with upward
titration as needed. Lorazepam tablets or solution can be placed
sublingually if the patient is unable to swallow. Lorazepam and midazolam
can be administered parenterally and are often indicated during the final
hours of life.

Intractable Pain at End of Life

When pain is poorly managed despite aggressive titration of available
therapies, several other options can be employed.137 First, thorough
assessment is needed to rule out potentially reversible etiologies. Because
the pain demands immediate attention, titration of the opioid therapy must
be aggressive while carefully preventing and treating adverse effects.
Additional therapies should be considered, such as corticosteroids, local

5295
anesthetics, ketamine, and other therapies. Bringing in a team approach is
crucial, including experts in pain and palliative care, as well as chaplains,
social workers, psychologists, and others, to address patient and family
suffering. When these interventions are unsuccessful, palliative sedation
may be considered.

Intravenous Lidocaine
Systemic administration of local anesthetics, such as lidocaine, has been
used to treat chronic pain.138–140 At subanesthetic doses, lidocaine blocks
neuronal function in active or depolarized neurons without interfering with
the normal function of other sensory or motor neurons. Although
historically used as a monthly infusion in chronic pain clinics, similar
protocols have been adapted for use in patients at end of life with
intractable pain. The dosage is generally 1 to 3 mg/kg administered
intravenously over 20 to 30 minutes.141 During the bolus infusion, pain
intensity scores often decline significantly. If effective, a continuous
infusion of 1 to 3 mg/kg/hour will be initiated. Immediate signs of toxicity
include numbness around the lips or a sensation of thickness of the tongue.
Due to the short half-life of lidocaine, the symptoms of toxicity are
transient and easily reversible by lowering the infusion rate. However,
toxicity has been reported at very low doses of lidocaine.142
In concert with the goals of care at this time of life, cardiac monitoring
is not usually performed nor are plasma levels of lidocaine obtained. If
subcutaneous administration is indicated due to lack of venous access, the
initial loading dose is administered over a longer time period (30 minutes
to an hour) and the response may be delayed by a few minutes.143 If
subcutaneous infusion is elected, more concentrated lidocaine solutions
allow for lower volumes to be infused. If the bolus dose is ineffective or
toxicity is unmanageable, the lidocaine challenge is discontinued and other
pain relief modalities must be selected.
The lidocaine infusion technique has been reported to be effective in a
child with cancer, using 35 μg/kg/min initially, with an increase to 50
μg/kg/min after several days.144 Other case reports suggest the efficacy of
continuous intravenous lidocaine in pediatric patients with opioid-resistant
cancer pain.145 The only randomized controlled trial of intravenous

5296
lidocaine for neuropathic pain from cancer using 5 mg/kg over 30 minutes
found no difference in analgesia.146 Much more research in this particular
area is needed.

Ketamine
Ketamine is an N-methyl-D-aspartate antagonist that can be given by a
variety of routes: oral, intravenous, subcutaneous, intranasal, sublingual,
epidural, intrathecal, and topical. It has been reported to improve pain
relief and reduce opioid requirements in a variety of pain syndromes
associated with cancer and other life-threatening illnesses.147–149 Although
it can be used earlier in the course of the disease trajectory, ketamine is
most commonly trialed in the face of intractable pain at the end of life.
In a small (n = 10) study of cancer patients who reported pain
unrelieved with morphine, a slow bolus of ketamine (0.25 mg/kg or 0.50
mg/kg) was evaluated using a randomized, double-blind, crossover,
double-dose design. Ketamine, but not saline solution, significantly
reduced the pain intensity in almost all the patients at both doses, with the
greatest effect being in those treated with higher doses. Adverse effects
included hallucinations in 4 patients and an unpleasant cognitive sensation
in 2 patients. These adverse effects responded to diazepam 1 mg
intravenously. Drowsiness was also significantly more likely to occur,
particularly with the higher dose. The investigators concluded that
ketamine improved morphine analgesia in a variety of difficult pain
syndromes; yet, central adverse effects can limit the use of this therapy.149
A study of young children and adolescents who were on high doses of
opioids and had uncontrolled cancer pain examined the effect of adding a
low-dose ketamine infusion. In 8 of 11 patients, ketamine infusions used
as an adjuvant to opioid analgesia provided improvement in pain and was
associated with opioid-sparing effects. This allowed reduction in opioid
dose that ultimately improved social interaction during this important
time.150
The usual oral dose of ketamine is 10 to 15 mg every 6 hours. Because
oral preparations are not commercially available in the United States, the
solution used for injection is administered orally, usually mixed with juice
or cola to hide the unpleasant taste. Parenteral dosing is typically 0.04

5297
mg/kg/hour with titration to a maximum of 0.3 mg/kg/hour. When given
parenterally or orally, the onset of analgesia is 15 to 30 minutes with a
duration of effect ranging between 15 minutes and 2 hours. A general
recommendation is to reduce the opioid dose by approximately 25% when
starting ketamine to avoid sedation. Severe side effects are generally
associated with doses of parenteral ketamine above 0.5 mg/kg and include
psychotomimetic phenomena such as dysphoria, nightmares,
hallucinations, excessive salivation, and tachycardia.
Although there are many small trials and case series that suggest
efficacy from ketamine, a well-designed randomized controlled trial found
no benefit.151 An updated Cochrane review concluded that there was
insufficient evidence to conclude that ketamine improves the effectiveness
of opioid treatment in cancer pain.152 Clearly, more research in this area is
needed.

Fears of Hastening Death

Pain at the end of life may be poorly managed due to fears of causing
respiratory depression. This is particularly true when family members
administering opioids at home express fear about causing their loved one’s
death. It can also occur in institutional settings where clinicians are
uncomfortable ordering or administering therapeutic doses of drugs.
Clinicians and family members also fear “giving the last dose” of an
opioid. Education is desperately needed. Respiratory depression is rare in
palliative care as most patients are opioid tolerant. A study of cancer
patients undergoing parenteral opioid titration for severe pain revealed no
change in end-tidal carbon dioxide, oxygen saturation, or respiratory
rate.153 Sykes and Thorns154 evaluated 17 studies that examined the use of
opioids at end of life. None of the five studies that explored opioid use and
survival found any relationship. Their own earlier study also found no
relationship between the dose or the timing of the opioid administration
and the time of death.155 These authors conclude that the doctrine of
double effect, which suggests it is ethical to employ a treatment intending
to obtain its beneficial effect (e.g., analgesia) but at the same time
recognizing that it may also have harmful effects (e.g., respiratory
depression or death), is not relevant. They also argue that it is potentially

5298
harmful to invoke this doctrine as it potentiates a myth: one that can lead
to greater fear and unrelieved pain. A study from the National Hospice
Database reported similar result: The dose of opioid had no appreciable
impact on the timing of death in patients with far-advanced disease.156
Several other reviews found a similar lack of association between opioid
doses or timing with survival.157,158

Suffering and Existential Distress

It may be very difficult to distinguish pain from other causes of suffering
in dying patients.159 Although the trend toward greater attention to pain is
positive, there is frequently little attention to the role loss, burden, sadness,
fear, isolation, and other existential concerns that can play at this time of
life.160 Several studies support the need for more useful definitions and
distinctions and to address the role of suffering in the individual’s life. For
example, one study asked hospice patients about suffering in an open-
ended interview, revealing that in the views of the 100 patients included in
this study, relief of pain and relief of suffering are not the same.161
Another study of health care professionals revealed that suffering was
viewed quite differently by chaplains, who defined this in spiritual terms,
versus pain professionals, who placed existential issues in the context of
pain.162
Using semistructured interviews, 381 patients with advanced cancer
were asked if they felt they were suffering and were also asked about
physical symptoms, social concerns, psychologic problems, and existential
issues. Approximately 25% reported they were suffering at a moderate-to-
extreme level. This suffering was strongly correlated with general malaise,
weakness, pain, and depression. Thus, although many patients with
advanced cancer do not consider themselves to be suffering, for those who
are suffering, it is a multidimensional experience related most strongly to
physical symptoms but with contributions from psychologic distress,
existential concerns, and social-relational worries as well.163 The
consequences of unresolved suffering are great, including a wish for
hastened death. In a study of 96 terminally ill elders, 15 acknowledged
significant suffering that resulted in a wish for a hastened death, and
several had even considered strategies to accelerate the dying process. In

5299
analyses of the interviews of these individuals, four critical themes
emerged: perceived insensitive and uncaring communication of a terminal
diagnosis by their health care professional, experiencing unbearable
physical pain, unacknowledged feelings regarding undergoing
chemotherapy or radiation treatment, and dying in a distressing
environment.164
Assessment of the whole person should be multidimensional, and an
interdisciplinary team is best equipped to address these broad issues. In
addition to a thorough pain and symptom assessment, patients should be
asked about the meaning of their lives, their sense of hope, the goals they
have for this time of their lives, and whether they are suffering. Suffering
is a deeply personal experience, accompanied by a wide range of emotions
and meanings.159 Inadequate assessment that only equates pain with
suffering can lead to inappropriate increases in opioids, without benefiting
their existential concerns, while leading to increased toxicity.165
When patients are identified as experiencing suffering, several
interventions can be useful. Life review allows the individual to reminisce
about life experiences, often leading to self-discovery of meaning in the
contributions they have made. Some people benefit by developing letters
or videotapes to loved ones to be read at a later date during anticipated
landmark events in the loved one’s life, such as college graduation,
marriage, or the birth of a child. One novel model to address psychosocial
and existential distress in the dying is called dignity therapy.166,167 This
brief, individualized approach to end-of-life care allows patients to discuss
issues that are most important to them and to describe the things they
would most want remembered as death draws near. These discussions are
recorded, transcribed, and developed into a document, which can be given
to family or loved ones. In one study of people with advanced cancer, 76%
reported a heightened sense of dignity, 68% reported an increased sense of
purpose, 67% reported a heightened sense of meaning, and 47% reported
an increased will to live.168 Family perceptions were also positive, with the
majority stating that the document developed by the dying loved one
helped during the grieving process and that the document would continue
to be a source of comfort for their families and themselves.169 Those who
are suffering often feel voiceless and having professionals witness and

5300
listen to their concerns in an empathic manner can be extraordinarily
therapeutic.

NONPHARMACOLOGIC TECHNIQUES
Nonpharmacologic therapies can be particularly useful during the final
hours of life. Cognitive-behavioral techniques, physical measures, and
education can be used as part of the multimodal treatment plan to reduce
pain and suffering, although few have been tested in end-of-life care.170
The patient’s and caregivers’ abilities to participate must be considered
when selecting any of these therapies, including their fatigue level,
interest, cognition, and other factors.171 Cognitive-behavioral techniques
include guided imagery,172 meditation,173 hypnosis,174 music175–177 and
art therapy,178 and other complementary therapies.179
Physical measures, including massage,180,181 reflexology,177 heat, and
other techniques,182 can produce relaxation and relieve pain. In a small
study of massage in hospice patients, reductions in blood pressure, heart
rate, and skin temperature were noted, suggestive of a relaxation effect.183
A potential benefit of all of these therapies is the ability to include family
members who are often seeking methods to provide comfort to their loved
one.
Family involvement in all aspects of care is crucial. Family caregivers
who rate their self-efficacy, or their ability to care for their loved one, as
high report much lower levels of strain as well as decreased negative mood
and increased positive mood. Ultimately, the caregiver’s self-efficacy in
managing the patient’s pain related to the patient’s physical well-being. In
dyads where the family caregiver perceived higher self-efficacy, the
patient reported having more energy, feeling less ill, and spending less
time in bed.184 As a result of these findings, Keefe and colleagues185
developed a partner-guided pain management training intervention that
they tested in 78 advanced cancer patients who met criteria for hospice
eligibility. Patients and their partners were randomly assigned to the
intervention or to usual care as the control condition. The partner-guided
pain management training protocol consisted of educational information
about cancer pain with systematic training of patients and partners in
cognitive and behavioral pain coping skills delivered in the patients’

5301
homes over three sessions. The partner-guided pain management protocol
significantly increased partners’ ratings of their self-efficacy for helping
the patient control pain and other symptoms. These family caregivers also
showed a trend toward reduced levels of caregiver strain.185
Although case reports and open-label trials of cognitive-behavioral,
physical measures, and educational interventions are reported to be very
effective in relieving symptoms at end of life, more research is
needed.170,186 Furthermore, most existing research has been conducted in
patients early in the disease trajectory, so more research is needed to
determine the potential value, no less the feasibility, of these interventions
in the final days and hours of life.

Palliative Sedation
Although the majority of individuals with pain at the end of life can obtain
relief with available therapies, some dying patients experience distressing
symptoms that cannot be controlled. In these cases, palliative sedation may
be considered. Several steps are crucial when implementing palliative
sedation. First, the team must be confident that all other reasonable options
have been explored, the disease is irreversible, and that death would be
expected in hours to days.187 Second, the patient and family should be
carefully informed about the risks and benefits of sedation, and they
should provide informed consent and agree with these plans. The entire
team (physicians, nurses, respiratory therapy, chaplains, social workers,
and others involved in the patient’s care) must have the opportunity to
discuss this option and agree as a team about the justification for the use of
palliative sedation and the details of the care to be provided. These are
generally complex cases that are emotionally stressful. All involved can
benefit from talking about the complex medical, ethical, and emotional
issues they raise. Decisions about hydration and nutrition as well as
resuscitation status (most centers require that the patient has do not
resuscitate orders) should be made prior to initiating sedation. Sedation
may be delayed if the patient is awaiting the arrival of a family member
from out of town. In some cases, light sedation may be used and reversed
once the relative arrives and then restarted and increased once the patient

5302
and loved one have had time to say goodbye. The American Academy of
Hospice and Palliative Medicine offers a position statement to guide
clinicians when opting to initiate palliative sedation.188
The agent most commonly employed drug for palliative sedation is
midazolam, although other benzodiazepines, propofol, or barbiturates can
be administered (Table 109.3).187 Benzodiazepines have anxiolytic,
muscle relaxant, sedative-hypnotic, anticonvulsant, antiemetic, and
amnesic effects. Their mechanism of action is through binding to GABA
receptors within the central nervous system leading to central nervous
system depression. Midazolam is the shortest acting agent within this
class, with an onset of action within 3 to 5 minutes after intravenous
injection and a half-life of 1 to 4 hours. These attributes, rapid onset and
relatively short duration, as well as the ability to administer it either
intravenously or subcutaneously makes this a useful drug in instituting
palliative sedation. Furthermore, it is stable with most other agents but is
incompatible with corticosteroids such as dexamethasone, betamethasone,
or methylprednisolone.

TABLE 109.3 Doses of Agents Used in Palliative Sedation189,197

Drug Route Bolus Dose Continuous Infusion
Midazolam IV, SQ 5 mg Starting dose 1 mg/h; usual maintenance
dose 20–120 mg/h
Lorazepam IV, SQ, SL, 0.5–2 mg PO, Starting dose 0.5–1.0 mg/h; usual
PO SL every maintenance dose 4–40 mg/h
1–2 h; 2–5
mg SQ or
IV
Chlorpromazine PO, IV, PR 10–25 mg
every 2–4
h
Haloperidol PO, IV, SQ 0.5–5 mg PO Starting dose 0.2 mg/h; maintenance 0.2–
every 2–4 0.6 mg/h
h; 1–5 mg
IV/SQ
bolus
Thiopental IV 5–7 mg/kg/h 20–80 mg/h
Pentobarbital IV 2–3 mg/kg Starting dose 1 mg/kg/h; titrate upward as
needed
Phenobarbital IV, SQ 200 mg, can 25 mg/h; maintenance dose 25–66 mg/h
repeat

5303
 every 10–
15 min
Propofol IV 20–50 mg 5–10 mg/h; may increase dose by 10
bolus; may mg/h every 15–20 min
repeat
IV, intravenous; PO, oral; PR, rectal; SL, sublingual; SQ, subcutaneous.

Propofol is an intravenous nonbarbiturate thought to enhance the

activity of GABA. The advantages of propofol include rapid onset and
short half-life. Although studies are lacking, the recommended dose of
propofol to treat refractory pain/suffering is 1 to 2 mg/kg via intravenous
injection over 5 minutes.189 The bolus may need to be repeated if the first
injection is ineffective. Bolus doses are followed by a maintenance
intravenous infusion of 2 to 10 mg/kg/hour, using the lowest dose needed
to suppress symptoms. Propofol is recommended for intravenous
administration; subcutaneous delivery has not been studied. Propofol
contains soybean oil and egg yolk phospholipid and therefore is
contraindicated for use in patients with egg hypersensitivity or soya
lecithin hypersensitivity.190
Family members must be provided sufficient information and support
during this time. In a multicenter study conducted in Japan, bereaved
family members of cancer patients who received sedation in seven
palliative care units were surveyed.191 The families reported that 69% of
the patients were considerably or very distressed before sedation. Although
the majority of families were satisfied with the treatment, 25% expressed a
high level of emotional distress. The factors associated with high levels of
family distress were poor symptom control after sedation, feeling the
burden of responsibility for the decision, feeling unprepared for changes in
the patient’s condition, feeling that the physicians and nurses were not
sufficiently compassionate, and a shorter time to their loved one’s death.
Regular monitoring of patient distress with timely modification of the
sedation protocol is vital, as is providing sufficient information and
sharing the responsibility for the decision. Family members require
emotional support to assist with their anticipatory and ongoing grief,
although a recent observational study found no negative impact on the
well-being of loved ones after witnessing palliative sedation.192 As the use
of palliative sedation increases, guidelines should be developed across

5304
settings and disciplines to ensure consistency. These guidelines must
articulate that this therapy is not euthanasia but is rather directed toward
treatment of symptoms.

Conclusion
The relief of pain during the final phase of life is vital for both the patient
who is experiencing this pain and for those at the bedside witnessing this
distress. All clinicians have the responsibility to learn how to assess pain
in the cognitively impaired and how to employ effective pharmacologic
and nonpharmacologic treatments. Empathic listening with attention to
suffering and existential distress will help improve the quality of life of the
dying. When pain remains severe, despite aggressive use of all appropriate
options, the team must carefully consider the use of palliative sedation,
along with the patient and their loved ones. All of this care involves the
skills of a well-functioning interdisciplinary team, combining the expertise
of each individual to provide optimal care to the most vulnerable of all of
our patients.

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179. Deng G, Cassileth BR, Yeung KS. Complementary therapies for cancerrelated symptoms. J
Support Oncol 2004;2(5):419–429.
180. Post-White J, Kinney ME, Savik K, et al. Therapeutic massage and healing touch improve
symptoms in cancer. Integr Cancer Ther 2003;2(4):332–344.
181. Polubinski JP, West L. Implementation of a massage therapy program in the home hospice
setting. J Pain Symptom Manage 2005;30(1):104–106.
182. Zappa SB, Cassileth BR. Complementary approaches to palliative oncological care. J Nurs
Care Qual 2003;18(1):22–26.
183. Meek SS. Effects of slow stroke back massage on relaxation in hospice clients. Image
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184. Keefe FJ, Ahles TA, Porter LS, et al. The self-efficacy of family caregivers for helping cancer
patients manage pain at end-of-life. Pain 2003;103(1–2):157–162.
185. Keefe FJ, Ahles TA, Sutton L, et al. Partner-guided cancer pain management at the end of life:
a preliminary study. J Pain Symptom Manage 2005;29(3):263–272.
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190. Baker MT, Naguib M. Propofol: the challenges of formulation. Anesthesiology
2005;103(4):860–876.
191. Morita T, Ikenaga M, Adachi I, et al. Family experience with palliative sedation therapy for
terminally ill cancer patients. J Pain Symptom Manage 2004;28(6):557–565.
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sedation on relatives’ experience of the dying phase and their wellbeing after the patient’s
death: an observational study. PLoS One 2016;11(2):e0149250.
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195. Paice JA, Portenoy R, Lacchetti C, et al. Management of chronic pain in survivors of adult
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197. Rousseau P. Palliative sedation in the management of refractory symptoms. J Support Oncol
2004;2(2):181–186.

5314
C H A P T E R 11 0
Ethical Principles that Support
Decision Making in Pain
Management: The Case of
Stopping Opioids
FAYE M. WEINSTEIN, CLAUDIA KOHNER, and STEVEN H.
RICHEIMER

New findings about long-term opioid use, as well as the new Centers for
Disease Control and Prevention (CDC) Guidelines for Prescribing Opioids
for Chronic Pain,1 are encouraging physicians to consider tapering or
weaning opioid treatment for chronic pain patients.2,3 This process of
weaning opioids can be difficult for both the patient and the physician. The
physical difficulties are addressed elsewhere, but the ethical and emotional
difficulties are rarely discussed. Although there is information in the
literature about ethical considerations and establishing trust with a patient
when starting a patient on opioids,4 we also need to understand the issues
involved in stopping opioid medication in a manner that maintains
physician–patient trust and ethical practice. Using a practical framework to
address these ethical and emotional issues can help the physician avoid
missteps that may result in disruption to the physician–patient relationship
and may lead to unwanted results, such as patient lack of receptivity to
other treatment options, patient difficulty with the titration regimen, and/or
patient dissatisfaction.

Background
Gunderman,5,6 a physician who writes on the ethics of the business of
medicine and leadership in medicine, has used Erik Erikson’s ideals as a
platform for his formulations. Erikson is credited with contributions to the

5315
fields of psychology, religion, and ethics.7 Erikson’s version of the Golden
Rule includes a “concern with universal justice and respect for the other,
where every person deserves recognition and mutual regard.”8(p153)
Following Gunderman’s5,6 lead, the authors of this chapter use
Erikson’s ethical theory to help guide the physician–patient relationship
during opioid cessation. Case vignettes of physicians taking patients off
opioid medication, along with analyses of the vignettes, are presented in
order to guide the reader in ethical analysis grounded in Erikson’s ethical
theory. Tools for building mutuality in the physician–patient relationship
are also covered.

MEDICAL ETHICS AND ERIKSON’S GOLDEN RULE

Medical ethics is typically discussed in terms of autonomy, beneficence,
and justice. The authors of this chapter believe that Erik Erikson’s
approach will provide a more practical framework.
Erikson presented his theory of the Golden Rule at the George W. Gay
Lecture Upon Medical Ethics, at Harvard Medical School on May 4, 1962.
Erikson’s reformulation of the Golden Rule emphasizes mutuality between
the physician and patient. For Erikson, medical ethics involves not only
rational decision making but also ideals related to a higher good.9 Ethical
acts are grounded in a sense of justice, a universal sense of responsibility
toward all human beings, and the need for mutual respect and
recognition.10 Erikson emphasized partnership and mutuality in the
physician–patient relationship, which provide the opportunity for growth
in both the physician and patient and bidirectional trust between physician
and patient. For Erikson,10(p233) the Golden Rule encourages that “it is best
to do to another what will strengthen you even as it will strengthen him—
that is, what will develop his best potentials even as it develops your own.”
Two primary elements of Erikson’s Golden Rule are trust and
mutuality.11 Investigating an ethical approach to a medical decision to stop
the use of opioids begins with an understanding of these components of
ethical practice.

TRUST
According to Erikson, over an individual’s life span, an “individual

5316
develops the propensity for ethics as he passes through eight
(developmental) stages.”12(p171) Developmental experiences in infancy
involving trust with caregivers form the bedrock on which the later seven
psychosocial stages will be experienced.13 To develop a sense of trust,
infants must be able to count on their caregivers to feed them, soothe them,
arouse or quiet them when needed, and mirror smiles and babbles.14 In an
optimal environment, the infant learns that the world is generally a safe
and consistent place and that people are mostly “good.” The infant gains
the strength of “hope,” which is the perception that, even if there is
waiting, one’s needs will be met and other people can be relied on to be
responsive to the one’s needs. Over the life span, trust is transformed and
provides a guiding principle for daily life and relationships with others.15
However, people with less optimal early lives may learn that their needs
will not be met and that people are unreliable; these individuals may
develop mistrust in their relationships as adults. Chronic pain patients may
have a greater likelihood of histories of early challenges in developing
trust16 and, therefore, go through life burdened with vulnerability to
mistrust.17
Trust is one of the central features of the physician–patient
relationship.18 Sass, a philosopher and ethicist, states that “trust becomes
the overriding principle and virtue that establishes and safeguards all
expert-lay interactions, particularly in the clinic.”19(p354)
Patient trust in a physician manifests as the expectation that the
physician will behave in a way that makes it safe for the patient to take the
risk of sharing personal information. Dimensions of physician behavior on
which patients are believed to base their trust in their physician are
“competence, compassion, reliability and dependability, and
communication.”18(p509) Pearson and Raeke18 identify the importance of
interpersonal trust, the trust built through repeated interactions with a
physician within which the patient learns over time that his or her needs
will be met in a predictable and consistent way despite changes in the
medical environment that may threaten trust.
O’Neill20 also describes trust building as a dynamic activity and views
physician trust as a partnership. Physician trust in a patient is not only
determined by the trustworthiness of the patient but can also be influenced

5317
by external factors, including media events, current research, racial
bias,21,22 practices of colleagues, and the physicians’ own experiences.23
With each patient, the physician’s trust is based on the assumption that the
patient’s motive is pain reduction and improvement in function and that
the patient is truthful in his or her self-report of symptoms and prior
treatment. Trust is confirmed via observation of patient adherence to a
treatment plan, patient efforts at participation in treatment, and prompt
patient communication with the physician if problems arise.4

MUTUALITY
According to Erikson,10(p231) the relationship between the parent and the
infant involves mutuality, which is a bidirectional process by which the
“partners depend on each other for the development of their respective
strengths.” Relevant to the focus of this chapter, Erikson10(p231) asserts,
“The fact is that the mutuality of adult and baby is the original source of
hope, the basic ingredient of all effective as well as ethical human action.”
The parent tries to understand the variety of needs in the child in regard to
soothing, eating, sleeping, and elimination. Parent and infant work to read
each other’s signals and to learn to regulate the amount of time that passes
between the expression of the need and satisfaction of the need. The work
of creating mutuality of interaction and communication is characterized as
a process of coordination, mismatch, and repair.24 Mutuality emerges from
patterns of physical (e.g., eye gaze, proximity, offering food), verbal
(patterns of speaking/vocalizing and responding), and affective (e.g.,
smiling) expressions. Erikson10 emphasized that through mutuality, the
parent reinforces his or her own sense of trust or revisits issues of mistrust.
Thus, mutuality is the focus on the relationship with others that becomes a
source of information about one’s identity and interactions with others.
Over the life span, mutuality is not exclusive to parent–child
relationships but manifests in different types of adult relationships, where
mutuality means “personal recognition, joint work, effective
communication, and understanding and respect for each other’s
roles.”25(p741)

MORALS AND ETHICS

5318
Erikson10 differentiated between morals and ethics, with ethics emerging
developmentally later than morals. In early life, the child not only learns to
trust whether needs will be met and comfort will be given. She or he also
learns that caregivers are a source of limit setting. The child internalizes
these prohibitions, forming the basis of morals, which are identified as
behaviors based on fear of consequences, such as “threats of abandonment,
punishment and public exposure, or a threatening inner sense of guilt, of
shame or of isolation.”10(p222) In adolescence, an individual starts to
transition from moral to ethical behavior, with behaviors and relationships
based on rigid ideas and ideologic devotion (e.g., “all my friends do this”).
Finally, in adulthood, the individual can become less ruled by rigid ideals
and becomes more able to act and relate to others on the basis of individual
worth and dignity. According to Erikson,10 this is the development of the
“ethical sense.”
Erikson’s distinction between morals and ethics resonates with Smith
and Newton’s26 three-phase evolution of physician ethics. According to
these authors, the Hippocratic Oath was the initial structure for the
physician–patient relationship with the “notion of authority,”26(p47) or
paternalism, toward the patient. Following a cultural shift to individualism,
the focus of ethical inquiry turned to patient autonomy, the second phase
in Smith and Newton’s26 three-phase evolution of physician ethics. This
led to rigid moral rules and formulas for the physician to follow in a
heightened climate of the protection of patient rights. Smith and Newton26
consider this era as the “essential formative period”26(p44) for the
emergence of the third phase in their three-phase evolution of physicians
ethics, one that is focused less on applying rules and more on valuing
“mutuality,”26(p56) “reflective experience,”26(p56) and “goals of human
dignity and dialogue”26(p56)—concepts in line with the foci of this chapter.
Erikson’s ethical sense has particular relevance when tested during
crises in which interactions with others trigger earlier psychosocial
tensions about trust. A physician-initiated cessation of a chronic pain
patient’s opioid prescription is potentially such a crisis. At this medical
juncture, issues of trust, mutuality, and the ethical sense are salient for
both patient and physician.
With its focus on trust and mutuality, Erikson’s Golden Rule can serve

5319
as the ethical foundation for the navigation of the medical crossroad of
cessation of opioid prescription in chronic pain patients. It provides a way
to find resolution to the tension that arises in this situation, to manage the
dynamic activity of trust, to build a partnership, and to promote mutual
growth.

Case Vignettes and Analysis

Three cases—each involving a type of challenge faced by physicians who
deal with cessation of opioid use for chronic pain patients—are presented
and evaluated to assess whether Erikson’s tenets of trust and mutuality in
his concept of the Golden Rule are evident or absent and whether the
physician was functioning from a moral sense or an ethical sense.
Table 110.1 lists the criteria—in the form of questions—that will be
used in assessing the cases for Erikson’s tenets of trust and mutuality in
the “Analysis” section for each of the three cases. Criteria numbers in
parentheses will be included in the analyses to link the concepts in the
analyses to the criteria. The purpose of these criteria is to provide a
framework for thinking about the basic concepts of Erikson’s ethical
theory in relation to the three cases.

TABLE 110.1 Criteria for Conceptualizing Physician–Patient

Interactions during Opioid Cessation for a Chronic Pain Patient:
Utilizing Erikson’s Golden Rule
C1. Are there shared goals between the physician and patient?
C2. Is the patient expressing trust?
C3. Is the physician using trust-building modes of communication?
C4. Do the physician and patient recognize the perspective of the other?
C5. Does the interaction strengthen both the patient and the physician?

CASE 1: OPIOID-INDUCED HYPERALGESIA

Background and First Attempt at Change of Treatment Plan
to Opioid Cessation
Ms. R is a 51-year-old married woman with a history of neck and low back
pain. She had been treated for about a year by Dr. T for pain related to
cervical and lumbar spondylosis, facet arthropathy, myofascial pain, and

5320
fibromyalgia. Ms. R travels a long distance to see Dr. T, and she has
communicated to her that it is worth spending the time in traffic to see her
because Dr. T is the first doctor who really listens to her and takes her
needs into account in making medical decisions. Ms. R’s pain medications
had been oxycodone 30 mg four times a day, gabapentin 600 mg two times
a day, and 50 μg fentanyl patch 50 μg per hour every 72 hours. Two visits
prior to the visit that is the focus of this discussion, in response to a pain
flare, Dr. T increased Ms. R’s medication to fentanyl patch 100 μg per
hour every 48 hours. In the next visit, Ms. R reported an improved pain
score. However, in the following visit, Ms. R was tearful, complained of
worse pain, and reported 9 to 10/10 pain on the pain numeric rating scale,
and she communicated that she was having trouble getting to the store,
socializing, and dealing with her son’s move out of the home to college.
As Dr. T reviewed prior notes in the computer, she responded that despite
the increase in the opioids, Ms. R had not improved in pain level or in
function. Dr. T added that the patient may have developed opioid-induced
hyperalgesia. Dr. T concluded that the patient needed to titrate completely
off the fentanyl patch and go on an opioid holiday before Dr. T could
reevaluate Ms. R for the need to be on chronic opioids. Dr. T noted in the
computer that Ms. R was very reluctant to follow her advice and told Ms.
R that, at this point, she did not think there were other options, saying,
“There is nothing more that I can offer you.” Dr. T looked up from her
computer and recommended an immediate wean of fentanyl from 100 μg
per hour to 75 μg per hour patch, decreasing to 50 μg per hour in 1 month,
25 μg per hour in 2 months, and then off. Ms. R said that she could not
believe that Dr. T would do this to her at this point, as she is a parent, too,
and from their time together, they have talked about the difficulty of a
child leaving home. Dr. T and Ms. R had talked in previous visits about
the patient’s son’s impending move from home. Dr. T encouraged Ms. R
to find other coping mechanisms to deal with her pain, perhaps regular
exercise, such as swimming. Ms. R became tearful, saying that she did not
know what went wrong, that before Dr. T was so understanding, and now
she is unwilling to help and is acting as if she does not know her anymore.
Ms. R challenged the assessment of hyperalgesia and expressed fear that
without opioids her pain could not be managed.

5321
Physician Consultation with a Colleague
After the visit, Dr. T felt unsettled by the interaction with Mr. R and
consulted with a colleague about the visit. Dr. T said that the visit “just felt
wrong” despite her confidence in the treatment plan. She admitted that she
felt betrayed by the patient’s resistance to her offer of help and that the
patient no longer trusted her judgment. Her colleague asked her, “What
was different for you in the visit?” Dr. T said that she felt disengaged from
the patient and that she was “just doing the mission of medicine.” She
reflected on what Ms. R’s experience of the interaction had been. She
pondered whether Ms. R also felt accused of poor judgment or pressured
about this sudden treatment change. Dr. T then recalled that she did not
engage the patient in their usual discussion about family or how the patient
could navigate yet another change.
Dr. T reflected on the themes of trust and betrayal that permeated both
her and Ms. R’s perspectives. The consultation with her colleague and
consequent self-reflection allowed Dr. T to not only attend to her own
feelings but also to reevaluate the interaction with Ms. R.

Modification in Engagement with Patient and Treatment

Plan following the Consultation and Reflection
During the next visit with Ms. R, Dr. T asked her how her son was doing.
Ms. R smiled and responded, and in a few moments, they began to discuss
the treatment plan from the last session. Ms. R reported that she felt that
she could not yet stop the fentanyl patch, but she proudly reported that,
despite sweating from the titration, she had decreased her oxycodone,
showing Dr. T the bottle with many pills left over. Dr. T praised Ms. R’s
success in cutting back on oxycodone. She requested Ms. R’s input on
what timing for titration of fentanyl would enhance her continued success.
Ms. R said that she is going to visit her son so she can see with her own
eyes that he has settled in and is doing well. Ms. R expressed that waiting
until after she visited her son would be helpful to her. Dr. T praised Ms. R
for her self-reflection and insight regarding the postponement of titration
until after her visit to her son. Dr. T utilized Ms. R’s perspective to
reconsider the treatment plan and postponed weaning off of opioids. Dr. T
prescribed a clonidine 0.1 mg patch to help with sweating and

5322
communicated to Ms. R the plan to begin the titration after the visit to her
son, when she has adjusted better to the stressors currently affecting her
life.

Analysis
Within the framework of the ethical principles described earlier, we can
see that in the visit in which Dr. T initially changed the treatment plan to
stop opioid use, she failed to use trust-building modes of communication
with the patient, which disrupted the trust that had been built in this
physician–patient relationship (C3). Threats to trust in adulthood may
trigger vulnerabilities that formed early in life and lead to frustration in the
current situation. Despite this difficulty, Erikson’s Golden Rule suggests
that challenges to trust, especially in a situation where there is disruption
to an expected receipt of care, can be optimized by both the patient and the
physician engaging in strategies to facilitate trust, to draw on the history of
trust built in the physician–patient relationship (C3). During the disruptive
office visit, Dr. T was driven by the pressure and frustration she felt about
the appropriate use of opioids (her goal) and failed to consider how her
stance would impact Ms. R (C1, C4).
Physicians may adopt various stances when engaging with patients
during difficult encounters, especially if the physician feels his or her
knowledge is being challenged or if the physician feels that his or her
ability to treat the patient is being undermined.27 Many physicians act in a
paternalistic fashion as a first-line response when perceiving urgency to
minimize risk and harm.28 The ethical nature of this type of physician
behavior is questionable because it fails to take into account the impact on
the patient of the physician’s decision making. Time with patients is
limited, creating additional pressure to adopt a forceful stance in order to
quickly communicate a judgment so that the patient will make a behavior
change.27 And for some physicians, offering up the rules of opioid
prescribing is a stance to demonstrate the veracity of their decision.26
Lorenzetti et al.27 reinforce the need to adopt principles of empathy and
effective communication and thus foster a relationship so that these stances
are not needed.
In this case, Dr. T reinforced her decision via an ultimatum that Ms. R

5323
must comply or nothing else would be offered in the relationship, which
represented a failure to recognize Ms. R’s perspective (C4). This
ultimatum left no room for Ms. R to consider the rationale behind the
decision, and she responded as if she were being punished (C2).
In Dr. T’s efforts to provide what she identified as appropriate care, she
did not consider that this represented to Ms. R a drastic change in care and
in the relationship (C4). Dr. T did not interact with Ms. R as she had in the
past, when the context and home life of the patient had been discussed,
physician behaviors that promoted Ms. R’s trust in Dr. T (C3). Dr. T did
not seem to be aware that this shift in style of engagement with Ms. R
would be difficult for Ms. R (C4), and Dr. T may have assumed that Ms. R
would automatically follow the titration plan. This lack of awareness by
Dr. T was interpreted by Ms. R as a violation of the trust in how care was
offered. The interaction shifted from being predictable and consistent—an
interaction in which Dr. T’s empathy was accessible to Ms. R—to Ms. R
coming to feel not being known and forced into a care plan not based on
her needs (C1, C2, C3, C4). Unfortunately, with this breach of trust, Ms. R
expressed reluctance to accept the change in treatment plan that Dr. T
recommended (C2). Despite Dr. T’s attempt to provide education about the
rationale for the change, Ms. R felt as if the “decision had nothing to do
with her or her needs” (C4).
As a result of Dr. T’s consultation with a colleague, she was able to
return to her previous fostering of trust and mutuality in her relationship
with Ms. R. This made it more likely for Dr. T to achieve an ethical state
with Ms. R (C5). A first step for Dr. T was to identify trust issues for both
her and Ms. R (C3). This is a difficult step—it requires the physician to
carefully examine the issues. It would be ideal if physicians could do this
before a potentially problematic interaction, but at least a distraught patient
can be a signal that the doctor should step back and reflect on interpersonal
issues with a patient. In fact, Dr. T. took a close look at where she might
have missed signals of need and distress from Ms. R. She also identified
where there had been disruption in their usual relationship (C4). In the
visit after the consultation, which from Dr. T’s side included the yield
from Dr. T’s reflection on what had happened with Ms. R in the previous
visit, Dr. T actively engaged with Ms. R, creating a dialogue, asking for

5324
Ms. R’s perspective, and providing a direct response to Ms. R’s feedback
(C3, C4). Dr. T validated for Ms. R her attempts to manage her feelings
about her son’s transition (C4). With renewal of trust and mutuality in the
engagement, the effectiveness and ethical quality of the treatment were
both enhanced (C5).

CASE 2: CHANGE IN THE CENTERS FOR DISEASE

CONTROL AND PREVENTION GUIDELINES
Background
The office manager of a family medicine practice received a call from the
Risk Management Department about Mr. B, a patient of Dr. J. Mr. B’s
complaint stated that his opioid medication had been stopped by Dr. J, a
physician in the medical practice, because of the new CDC guidelines. Mr.
B has a history of complex regional pain syndrome (CRPS) and had been
treated by Dr. J for many years. The office manager recalled their struggle
to find a treatment regimen that worked for Mr. B and Mr. B’s success at
stopping smoking in an effort to control pain symptoms. Mr. B reported to
Risk Management that Dr. J told him that Dr. J had become too scared of
the CDC and Drug Enforcement Administration (DEA) to prescribe
opioids any longer. Mr. B feared not getting adequate pain control without
opioids. He started smoking again because he was so upset. Mr. B told
Risk Management that Dr. J offered an epidural injection, but Mr. B is still
waiting for the insurance company to authorize this treatment.

Analysis
In this case, the physician had difficulty coping with an unexpected change
in prescribing guidelines. Dr. J felt angry and trapped. After many years of
practice, based on then-current guidelines about the appropriateness of
long-term use of opioids, he now had a large cohort of long-term patients
who are taking opioids. With the change in CDC guidelines, based on new
evidence of the pitfalls of long-term use of opioids, Dr. J felt that he was
being blamed by the CDC for getting his patients dependent on a type of
medication that is not good for long-term use.
Using the perspective of Erikson’s Golden Rule, Dr. J’s own sense of
trust in the foundations of how to practice ethically in pain management

5325
was threatened by shifting CDC guidelines. In this particular case, he may
have been revisiting a crisis of trust similar to ones that he had experienced
in prior situations where the rules had been changed. His frustration about
the unexpected demands from the CDC guidelines impaired his ability to
maintain trust in his prescribing of opioid medication. With Mr. B, he
made an abrupt decision to stop prescribing opioids based on his
perception of the rigid expectation of the CDC authority (meeting Dr. J’s
goals), instead of engaging in self-reflection and trust-building
communication with his patient (C1, C3). Dr. J’s conformity to a rigid
ideology and his inflexibility in his application of the CDC guidelines left
him lost in defensiveness and rejection of his patient, unable to shift into
the “unique needs of the present moment” (C5).12(p172) Dr. J functioned
with the moral sense of young adulthood rather than with the ethical sense
of later adulthood, leaving Mr. B feeling so abandoned by and angry at Dr.
J (C2) that Mr. B filed a complaint against Dr. J.
Had Dr. J functioned according to Erikson’s Golden Rule, there would
have been alternative approaches to dealing with the situation with the
potential for more beneficial outcomes for this crisis. Specifically, had Dr.
J reflected on his and Mr. B’s prior successful experience with smoking
cessation, Dr. J could have talked to Mr. B about Mr. B having been able
previously to tolerate a painful loss of a substance he had relied on, which
would have been an interaction that would have strengthened both patient
and physician (C5). This discussion could have laid a foundation for Mr. B
facing the prospect of cessation of opioids. Furthermore, Dr. J could have
reminded Mr. B that he had been able weather this challenge because of
his trust (C3) in Dr. J and that after cessation of smoking, Mr. B had noted
some reduction in his pain. By “renewing prior achievements in
trust,”15(p255) Dr. J could have helped Mr. B counteract his sense of distrust
in his ability to manage the situation as well as his sense of distrust in the
physician. This alternative approach could have avoided the breakdown in
Mr. B’s trust in Dr. J and subsequent call to Risk Management (C3).
In terms of the threat of the change in CDC guidelines to Dr. J as a
physician, another possibility would have been for Dr. J to reflect on how
hard it is for him and for other physicians to cope with the change in CDC
guidelines regarding prescribing opioids, especially when what they were

5326
taught and practiced is now being identified as wrong. He might have
identified that all of these changes make him feel off-kilter and, in
addition, that he has to get used to the change in his practice. Although this
is difficult, he could have recalled that he had navigated similar challenges
in the past. For instance, as a family medicine physician, Dr. J had had to
change how he prescribed antibiotics.29 That transition had been difficult,
but Dr. J had felt backed up by science and was able to adapt. If Dr. J
could have identified that he has survived prior challenges, he could have
drawn on these previous experiences to remind him of his achievements.
He could have reapplied the same coping he had used to survive the other
situations to the current situation, which would have strengthened both
him and his patient (C5).
Applying the concept of mutuality would have been useful. Mr. B may
have appreciated hearing Dr. J say that he saw how the change could be
upsetting to the patient and that he (Dr. J) is distressed at the changing
rules. This bidirectional sharing could have been strengthening for both
patient and physician and could have contributed to both the effectiveness
and ethicality of the handling of the crisis (C4, C5).

CASE 3: OPIOID PRESCRIPTIONS FROM OTHER

PHYSICIANS FOUND IN CHECK OF STATE DRUG
MONITORING PROGRAM
Background
Ms. A, a single woman in her 30s, came to Dr. S after extensive treatment
by another pain specialist. She had chronic low back pain associated with
post-laminectomy, or failed back syndrome. Her insurance no longer
covered her prior physician. She was on high doses of opioids—higher
than Dr. S usually prescribed. Her prior medical records documented Ms.
A’s report that she had not responded to various spinal injections or to
physical therapy, but she was stable on fentanyl patch, 75 μg every 3 days
plus hydrocodone/acetaminophen 10/300 three times a day. Dr. S found
himself struggling with issues of prejudging—Ms. A was heavily tattooed
and not working, and there was no clear pain source for her chronic pain.
Dr. S had to make a conscious effort to not to assume—based on
appearances—that the patient was inappropriately seeking opioids. Dr. S

5327
explained to Ms. A his concerns for safety given her opioid dose of
approximately 180-mg morphine equivalents per day. He specifically
addressed the issue of hyperalgesia and his long-term goal of her coming
off opioids completely. Ms. A said that the only helpful treatment for her
pain is opioids, and she did not want to come off of them completely. They
agreed to go down slowly. Dr. S was willing to prescribe her medications
if she would agree to lower her fentanyl dose over the next 2 months to 50
μg every 3 days. Ms. A also signed a standardized treatment agreement,
which includes informing the signer that all controlled substances must be
prescribed by Dr. S. Ms. A also signed that she understood that Dr. S
would monitor her for usage of any controlled substances by any other
provider.
Dr. S continued to prescribe these medications for the next year, until a
check of the state drug monitoring program revealed three extra
prescriptions for hydrocodone/acetaminophen 10/300 mg from other
physicians. Ms. A’s violation of the treatment agreement led Dr. S initially
to feel that Ms. A could not be trusted. However, he reminded himself that
there is a difference between not being trustworthy at all and not being
trustworthy to handle a specific drug. Ms. A might be trusted with other
drugs and procedures.
Dr. S anticipated that when he brought the results of the check of the
state drug monitoring program to Ms. A’s attention, she would angrily
deny the problem and then storm out of the office, never to return. Dr. S
braced himself for Ms. A’s anger at her next office visit. In fact, at first,
Ms. A did deny the extra prescriptions, but not angrily, and then she
apologized for the “mistake” and promised to not “mess up” again. Dr. S
explained to Ms. A that she is not a safe candidate for opioids. He told her
that he would be happy to continue to treat her but without opioids. Again,
Dr. S braced himself for anger, but to his surprise, Ms. A said, “Okay
doc,” and she continued to treat with Dr. S.
Over the next few months, Dr. S started Ms. A on physical therapy and
pain psychology (which she discontinued after two sessions) and tried
facet joint injections. Ms. A reported that none of these treatments was
helpful, and after a few months, she started requesting that they resume
opioids because the pain is so bad. Dr. S continues to wrestle with himself

5328
that perhaps this is one of the relatively few patients who do benefit from
long-term opioids, but he reminds himself and Ms. A that opioids are too
seductive and dangerous for her. Ms. A is not happy that Dr. S continues
to decline to prescribe opioids, but she has continued to treat with Dr. S,
and the state drug monitoring program indicates that she is not receiving
opioids anywhere else. Dr. S feels good that Ms. A has “stuck with me.”

Analysis
In this case, Dr. S’s insight and self-reflection, which laid the foundation
for sound communications with Ms. A (C3), helped him to effectively and
ethically deal with a variety of trust-related issues regarding opioid use and
cessation. Some of the trust issues were related to himself, and others
stemmed from the patient’s presentation and actions. The patient’s unclear
pain source, use of a high level of opioids, and prejudicetriggering
appearance caused concern for Dr. S about whether he could trust Ms. A.
In order to clearly see and respond to her needs, Dr. S had to contain his
initial reaction that she was an untrustworthy patient. However, Dr. S
reflected on his impulse to mistrust and waited for more input before
reacting. He saw that the patient spoke reasonably about her use of opioids
and that her medical records correlated with her self-report. Dr. S’s
capacity to wait created (1) a space for more information about the patient
to emerge, (2) a physician–patient dialogue about safety, and (3) the
patient signing a treatment agreement—three factors that had the potential
to enhance mutual trust between patient and physician (C3). This trust may
have helped Ms. A to agree to the initial titration of the fentanyl and have a
reasonable reaction when confronted with obtaining opioids from other
sources (C2). When Ms. A went against the treatment agreement, Dr. S
initially felt a sense that she could not be trusted. However, he tried to
understand her perspective of trying many treatments without results (C4).
He reminded himself that there is a difference between not being
trustworthy at all and being a person who cannot be trusted to handle a
specific drug. Dr. S reasoned that Ms. A could be trusted with other drugs
and procedures that he offered but not with opioids. His continued
relationship with Ms. A enhanced his confidence in his decision not to
prescribe opioids for her. Dr. S continues to feel good that the patient has

5329
stayed in treatment with him (C5).
Of particular note in this case is Dr. S’s success in both avoiding
behaviors that could have triggered feelings of abandonment in the patient
and in implementing limit setting with the patient—in contrast with Case 1
and Case 2. This resonates deeply with Erikson’s Golden Rule. Dr. S’s
way of engaging with Ms. A is like a parent with an infant who—through
fostering trust and communicating mutuality—can instill in the infant the
strength of hope.11 It is hypothesized that Ms. A could sense Dr. S’s
commitment to working with her and that feeling his commitment helped
her in accepting that he would no longer provide opioids as part of the
treatment plan (C4).
Case 3, in contrast with Case 1 and Case 2, illustrates Erikson’s10
distinction between moral rules and ethical rules. The physicians in Case 1
and Case 2 were guided by moral rules, “fear of threats to be forestalled.
These may be outer threats of abandonment, punishment and public
exposure, or a threatening inner sense of guilt, or shame or of
isolation.”10(p222) Dr. S’s actions were based on a physician–patient
relationship, grounded in ideals rather than rigid adherence to rules.10(p222)
This led to thoughtful action that girded both physician and patient for the
vicissitudes of pain management in the face of opioid prescribing and
cessation (C5).

Building Trust through Mutuality

Three tools can help physicians build trust through mutuality. These tools
are especially helpful for physicians who treat chronic pain patients:
• Dialogue
• Empathy
• Narrative medicine

DIALOGUE
From the analysis of Case 1, we saw the patient’s loss of trust in the
physician undermining the physician’s efforts to help the patient. Smith
and Newton26(p54) encourage “meaningful dialogue” between patient and
physician. They encourage the physician to see the patient as a person, to

5330
connect with that person, and to be a person (in addition to a physician)
during the interaction.26
Reflecting back on Erikson’s view of mutuality, what is needed is a
willingness on the part of the physician to not only try to read the verbal
and nonverbal signals of the patient but also to acknowledge, discuss, and
reflect on them. Physicians who can engage in this type of dialogue may
also ameliorate their own frustration and promote personal growth in the
physician. Thus, both physician and patient may benefit from an ethical
interaction. Allowing oneself to participate in dialogue with a patient can
be an authentic way of connecting beyond the mask of professionalism.
The realization of change is illustrated in Stephen Sondheim’s song “It
Takes Two” from the musical “Into the Woods,” where the baker has
become a better and different man by including his wife’s input and
participation in a critical venture. The baker’s wife noted that the baker
had become more “daring,” confident, “sharing,” and “openhearted.”30

EMPATHY
Physicians who want to have mutuality in their interaction with their
patients may need to be refreshed in the skills needed to do this. Empathy
is a skill that can promote mutuality.
Hojat et al.31 uses Mercer and Reynolds’s 2002 paper “Empathy and the
Quality of Care” to characterize four abilities that a physician uses to
engage with a patient with empathy:
• Cognitive. The physician identifies and understands the patient’s
emotional experience.
• Emotive. The physician imagines and relates the patient’s emotional
experience to his or her own experience.
• Moral. The physician is motivated to express his or her understanding
of the patient’s experience to the patient grounded in the physician’s
humanity.
• Behavioral. The physician communicates to the patient his or her
understanding of the patient’s experience.
Empathy training offers strategies to bring trust building and mutuality
to a difficult physician–patient interaction.27 Specific communication
strategies include (1) techniques to enhance physician–patient dialogue,

5331
(2) active listening, (3) validating emotion, and (4) exploring alternative
solutions.27(p423) For instance, during the visit in which the physician in
Case 1 decided to move toward cessation of opioids, the physician was
facing her computer, not facing the patient. According to Ambady and
Rosental,32 eye gaze and contact is needed for mutuality and for
transmitting empathy.
Researchers believe that it is possible to teach and for physicians to
learn and practice empathy, or at the very least act empathetically.33 A
systematic review of published literature on empathy training interventions
that were quantitatively evaluated to detect changes in empathy among
medical students, residents, fellows, and physicians found that 66% (42
out of 64) of reviewed studies reported a statistically significant increase in
empathy.33
Practice of empathic techniques may help the physician become
genuinely empathic.34 To further the goal of being able to “treat each
patient as a person, not an illness,”35 the authors of this chapter suggest
that pain physicians engage in team meetings that include discussions of
the patients’ personal histories and the potential difficulties with
connection with an individual patient.

NARRATIVE MEDICINE
Charon36 has written about the use of narrative theory and methods in the
practice of bioethics. The goal of these methods, called narrative-based
medicine (NBM), per Charon,36(p1897) is to “practice medicine with
empathy, reflection, professionalism and trustworthiness.” It is a pathway
toward the “authentic engagement [that] is transformative for all
participants,”36(p1898) thus invoking the tenet of mutuality that anchors
Erikson’s Golden Rule. She describes the contributions of NBM to both
patient and physician. For the patient, NBM makes the patient feel better
understood, more hopeful, and more comfortable asking difficult
questions. For physicians who can engage with their patients using NBM,
it makes the physicians a reflective practitioner with an enhanced ability to
“identify and interpret their own emotional responses to patients, make
sense of their own life journeys” and achieve a more accurate
understanding of illness and suffering.36(p1899) Peterkin37 offers a list of

5332
some of the basic physician behaviors of NBM, which include the
following:
1. “Ask open-ended questions.”
2. “Do not interrupt.”
3. Ask about suffering
4. “Learn your patients’ stories.”
5. “View noncompliance as a blocked narrative, not as patient
stubbornness.”
6. Ask the question “What do you think is going on?”
7. Ask yourself, “Where did we leave the thread of our story the last
time?”
Charon36 recommends training in narrative skills as well as reading,
reflective writing, and authentic dialogue with patients.

Conclusion
Crises in trust occur during physician–patient encounters involving opioid
cessation. By addressing trust issues in these interactions via mutuality,
physicians may be able to help with the ethical distress that comes with
having to balance their patient’s best interests with cultural swings of the
pendulum toward and away from opioid prescribing. Erikson’s Golden
Rule provides a framework for navigating the challenge of cessation of
opioids in chronic pain patients.

References
1. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain
—United States, 2016. MMWR Recomm Rep 2016;65(1):1–4.
2. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain
—United States, 2016. JAMA 2016;315(15):1624–1645.
3. McCarberg B. How opioid prescribing guidelines may affect (help or hinder) a primary care
physician’s ability to provide pain management. Paper presented at: the American Academy
of Pain Medicine 33rd Annual Meeting; March 16–19, 2017; Orlando, FL.
4. Victor L, Richeimer SH. Trustworthiness as a clinical variable: the problem of trust in the
management of chronic, nonmalignant pain. Pain Med 2005;6:385–391.
5. Gunderman RB. We Make a Life by What We Give. Bloomington, IN: Indiana University
Press; 2008.
6. Gunderman RB. Leadership in Healthcare. London: Springer; 2009.
7. Snarey J, Bell D. Erikson, Erik H. In: Dowling EM, Scarlett WG, eds. Encyclopedia of
Religious and Spiritual Development. Thousand Oaks, CA: Sage; 2006:146–150.
8. Browning DS. Generativity, ethics, and hermeneutics: revisiting Erik Erickson. In: Browning

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 DS, Witte J, series eds. Christian Ethics and the Moral Psychologies. Grand Rapids, MI: Wm.
B. Eerdmans; 2006:146–165. Religion, Marriage, and Family.
9. Erikson EH. The Golden Rule and the cycle of life. Harvard Medical Alumni Bulletin. Winter
1963.
10. Erikson EH. The Golden Rule in the light of new insight. In: Insight and Responsibility:
Lectures on the Ethical Implications of Psychoanalytic Insight. New York: Norton; 1964:217–
243.
11. Conn WE. Erik Erikson: the ethical orientation, conscience and the golden rule. J Relig Ethics
1977;5(2):249–266.
12. Piediscalzi N, Erik H. Erikson’s contribution to ethics. J Relig Health 1973;12(2):169–180.
13. Erikson EH. Childhood and Society. 2nd ed. New York: Norton; 1963.
14. Mooney CG. Chapter 3: Erik Erikson. In: Theories of Childhood: An Introduction to Dewey,
Montessori, Erikson, Piaget & Vygotsky. St. Paul, MN: Redleaf Press; 2000:53–76.
15. Perry TE, Ruggiano N, Shtompel N, et al. Applying Erikson’s wisdom to self-management
practices of older adults: findings from two field studies. Res Aging 2015;37(3):253–274.
16. Van Houdenhove B. Assessing adverse childhood experiences in chronic pain: it does matter.
Clin J Pain 2006;22:584–585.
17. Vogel-Scibilia SE, McNulty KC, Baxter B, et al. The recovery process utilizing Erikson’s
stages of human development. Community Ment Health J 2009;45(6):405–414.
18. Pearson SD, Raeke LH. Patients’ trust in physicians: many theories, few measures, and little
data. J Gen Intern Med 2000;15:509–513.
19. Sass HM. The clinic as testing ground for moral theory: a European view. Kennedy Inst Ethics
J 1996;6:351–355.
20. O’Neill O. Autonomy and Trust in Bioethics. Cambridge, United Kingdom: Cambridge
University Press; 2002.
21. Moskowitz D, Thom DH, Guzman D, et al. Is primary care providers’ trust in socially
marginalized patients affected by race? J Gen Intern Med 2012;26(8):846–851.
22. Thom DH, Wong ST, Guzman D, et al. Physician trust in the patient: development and
validation of a new measure. Ann Fam Med 2011;9:148–154.
23. Gooberman-Hill R, Heathcote C, Reid CM, et al. Professional experience guides opioid
prescribing for non-cancer pain in primary care. Fam Pract 2010;0:1–8.
24. Tronick E, Beeghly M. Infants’ meaning-making and the development of mental health
problems. Am Psychol 2011;66(2):107–119.
25. Watt G. A social institution based on mutuality and trust. Br J Gen Pract 2011;61(593):741.
26. Smith DG, Newton L. Physician and patient: respect for mutuality. Theor Med Bioeth
1984;5:43–60.
27. Lorenzetti R, Jacques CH, Donovan C, et al. Managing difficult encounters: understanding
physician, patient and situational factors. Am Fam Physician 2013;87(6):419–425.
28. Genuis SJ. Dismembering the ethical physician. Postgrad Med J 2006;82(966):233–238.
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treat pain. PBS NewsHour. https://www.pbs.org/newshour/show/as-opioid-epidemic-worsens-
rethinking-how-doctors-are-taught-to-treat-pain. Accessed April 29, 2017.
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31. Hojat M, Gonnella JS, Mangione S, et al. Empathy in medical students as related to academic
performance, clinical competence and gender. Med Educ 2002;36:522–527.
32. Ambady N, Rosental R. Nonverbal communication. In: Friedman H, ed. Encyclopedia of
Mental Health. Vol 2. San Diego, CA: Academic Press; 1998:775–782.
33. Kelm Z, Womer J, Walter JK, et al. Interventions to cultivate physician empathy: a systematic
review. BMC Med Educ 2014;14:219.

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34. Taigman M. Can empathy and compassion be taught? JEMS 1996;21(6):42–48.
35. Hirsch EM. The role of empathy in medicine: a medical student’s perspective. Virtual Mentor
2007;9(6):423–427.
36. Charon R. The patient-physician relationship. Narrative medicine: a model for empathy,
reflection, profession, and trust. JAMA 2001;286(15):1897–1902.
37. Peterkin A. Practical strategies for practising narrative-based medicine. Can Fam Physician
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C H A P T E R 111
Training Pain Specialists
JAMES P. RATHMELL and JAN VAN ZUNDERT

The Evolution of Pain Medicine as a Subspecialty

It is impossible for any physician to become an expert in every field. As
knowledge expands and the need for detailed skills arises, the natural
progression is for specialization to ensue. There has long been a
discomfort with specialization despite an unflagging progression in that
direction. The urge to both specialize and remain unspecialized dates back
to the earliest recorded history of medicine. The first specializations were
between the barber-surgeons and the internists, and a rivalry of sorts
remains to this day. Writing about Ambrose Paré, the 16th century
physician who elevated the role of the barber-surgeons to that of other
physicians, the present-day surgeon and historian Sherwin Nuland1 reflects
on the ongoing distinction between internist and surgeon:
Surgery is an exercise in the use of the intellect. Heckling internists,
with tongues barely in check, would prefer that surgical specialists be
viewed merely as dexterous craftsman who carry out the routing
errands assigned to them by their more cerebrally endowed medical
overseers. I attribute this teasing raillery to a kind of good-natured
fraternal envy, not so much of our celebrity status, but rather of the
visibility of the cures we surgeons achieve and the particular personal
gratification we have while doing it.
In the United States, anesthesiology has progressed toward further
specialization, first with the establishment of critical care; then pain
management (now called pain medicine); and more recently, pediatric
anesthesiology, cardiothoracic anesthesiology, and obstetric
anesthesiology. The addition of pain medicine as a subspecialty of
anesthesiology is just one recent example of the growth of medical

5336
specialties. With specialization comes a conscious effort to focus practice
to become intricately familiar with a more limited realm. The obvious
result is a loss of the skills and knowledge needed to practice in the
broader parent specialty. In pain medicine, many now view this as a full-
time vocation. The scientific meetings and journals that keep pain
medicine specialists up-to-date have little overlap with those that are
designed to serve anesthesiologists practicing in the operating room. The
only common thread between the technical skills needed in the pain clinic
and those required for anesthesiology in the operating room is expertise
with neural blockade, which is one of several important skill sets needed in
pain medicine. The rapid expansion of knowledge in the causes and
complications of acute and chronic pain, particularly in the
neurobehavioral sciences, has led to a growing recognition that the pain
medicine practitioner must acquire a vastly different skill set than those
practicing anesthesiology, including expanding their skills as
diagnosticians.
Much has been written about the origins of pain medicine as a distinct
discipline, and anesthesiologists have played a primary role since the
start,2 as have specialists in neurology, psychiatry, neurosurgery, and
physical medicine and rehabilitation.3 Anesthesiology really started with
the introduction of effective general anesthetics in the mid-19th century,
when surgical pain could be separated from operation. Almost 100 years
later, the late John Bonica, an anesthesiologist and recognized father of the
specialty we now call pain medicine, developed his career promoting
multidisciplinary pain care and formal training of specialists. From his
life’s work, we now have extensive ongoing efforts to recognize and treat
pain effectively, to train subspecialists, and to conduct basic and clinical
research to further our understanding of pain and its treatment. The
International Association for the Study of Pain (IASP) founded in 1974; its
US chapter, the American Pain Society; and the journal Pain are legacies
left by Dr. Bonica for our patients. Dr. Bonica began his practice with a
focus on regional anesthesia techniques but soon came to realize that these
techniques were inadequate to meet the needs of his patients with chronic
pain and that he could not incorporate the growing scientific evidence of
the importance of neurobehavioral factors. This realization evolved to the

5337
belief that developing the field of pain as a separate clinical discipline and
treating chronic pain competently required the intellectual input and
clinical skills of several other specialties. He published the first edition of
this seminal textbook, The Management of Pain, toward that end in 1953.4
It is noteworthy that IASP presidents have backgrounds from
anesthesiology, dentistry, neurology, neurophysiology, neurosurgery,
psychiatry, and psychology. All share a common intellectual passion and
achievement, as well as clinical dedication, to developing pain research,
teaching, and clinical care in pain medicine.
Accredited fellowship training in pain medicine is a relatively recent
development. Prior to 1992, training was frequently obtained in academic
anesthesiology departments, including those of John Bonica, Philip
Bridenbaugh, Harold Carron, Daniel Moore, Prithvi Raj, Alon Winnie, and
others, and subsequently in programs run by their trainees. These
unaccredited programs advanced the specialty, widened interest in pain
medicine as a career, and propagated anesthesiology-based pain care in
smaller and smaller communities across the country. Other specialists also
contributed to the development of the practice model of pain care. Many of
the early leaders of pain medicine were from other specialties, and they
trained fellows in unaccredited programs as well. Multispecialty entrance
into pain medicine training became a tradition in several cities, including
Boston, under Daniel Carr (Harvard, Massachusetts General) and Carol
Warfield (Harvard, Beth Israel); New York, under Kathy Foley, Russ
Portenoy, and Bob Breitbart (Memorial Sloan Kettering Cancer Center);
and Seattle, under John Loeser, John Bonica’s successor (University of
Washington), among others. For example, one of the authors (Rollin M.
Gallagher) provided fellowship training in chronic pain rehabilitation at
State University of New York at Stony Brook and Drexel University
College of Medicine to doctors with residency backgrounds in neurology,
psychiatry, physiatry, and family practice before accreditation was
possible. Outside of the United States, with the notable exception of
Australia, this type of informal training remains the rule for those seeking
expertise in pain medicine. In the United States, the American Board of
Anesthesiology (ABA) developed interest in certifying pain medicine
training. The failure of coalition of the boards of anesthesiology,

5338
psychiatry and neurology, physical medicine and rehabilitation, and
neurosurgery in 1990 to form a conjoint American Board of Medical
Specialties (ABMS) board led the ABA, under the leadership of Bill
Owens in his roles on both the ABA and the Residency Review Committee
(RRC) for Anesthesiology, and through his representations of the
subspecialty to the ABMS, to begin accrediting formal training programs
and certifying physicians in 1992 through the Accreditation Council for
Graduate Medical Education (ACGME). Steve Abram and John
Rowlingson were both key members of the group that assisted Dr. Owens
in moving the new subspecialty forward.
The number of ACGME-accredited programs (Fig. 111.1) and the
number of trainees in accredited programs have grown steadily over the
past decade, reaching just under 100 training programs by 1999 that train
just over 300 new pain specialists each year (Fig. 111.2). The ABA
working in parallel with the ACGME developed a subspecialty
certification examination in pain medicine, first named the “Certificate of
Added Qualifications in Pain Management,” now titled “Subspecialty
Certification in Pain Medicine.” The first exam was given in 1993. The
number of candidates sitting for the examination has steadily grown since
the first exam was given.

FIGURE 111.1 The Number of Accreditation Council for Graduate Medical Education
(ACGME)-accredited pain medicine training programs in the United States by primary sponsoring
medical specialty over time through 2015. (Data provided by the American Council on Graduate

5339
Medical Education.)

FIGURE 111.2 The number of new board-certified pain medicine specialists in the United States
by specialty over time through 2015. ABMS, American Board of Medical Specialties. (Data
provided by the American Board of Anesthesiology.)

Dr. Bonica’s original push to develop multidisciplinary pain care

recently evolved into collaboration between four specialties agreeing to a
single and unified set of program requirements for all ACGME-accredited
pain fellowships regardless of sponsoring specialty. Consequently, in
1999, the ABA invited representatives of the American Board of
Psychiatry and Neurology (ABPN) and the American Board of Physical
Medicine and Rehabilitation (ABPMR) to join the ABA’s Pain
Management Examination Committee to broaden the examination beyond
its prior focus on regional anesthesia, and, in 2000, the ABPN and
ABPMR began issuing certificates of subspecialty certification in pain
management to those diplomates who passed the expanded ABA
examination. Between 2002 and 2006, the ACGME, working in
collaboration with the ABA, ABPN, and ABPMR, developed new
program requirements for pain fellowship training programs aimed at
improving the quality of education in pain medicine and promoting a
multidisciplinary approach to care. The new program requirements were
adopted in 2006, and the number of programs achieving ongoing
accreditation under these broader and more rigorous requirements initially
declined by nearly 20% (see Fig. 111.2) and has rebounded in more recent
years, with anesthesiology programs being replaced by those sponsored by

5340
physical medicine and rehabilitation. A 2015 snapshot of the distribution
of board-certified pain specialties by primary medical specialty is shown in
Figure 111.3. Equally important in the evolution of the discipline is the
creation of academic physicians within the fellowships who undertake
research programs to add new knowledge to this needed field of medical
practice.

FIGURE 111.3 Distribution of the primary medical specialty of physicians board certified in the
subspecialty of pain medicine in the United States in 2015. (Data provided by the American Board
of Anesthesiology.)

Pain and its consequences draw on resources from all medical

disciplines. Dr. Bonica’s experiences during World War II suggested that
each medical specialist had unique expertise to bring to patients suffering
in pain, hence his consistent and effective promotion of a multidisciplinary
process for pain care. Also thanks largely to Dr. Bonica, anesthesiology
has led the development of formal training programs. Indeed, the majority
of currently accredited programs reside within academic anesthesiology
departments, and most program directors are anesthesiologists. Specialists
from other disciplines have also focused their clinical and research efforts
on pain. The most obvious example is neurology where the majority of
clinical treatment and research about headache and peripheral neuropathy
has arisen. Physical medicine and rehabilitation has also long had a focus

5341
and expertise in functional restoration, and physiatrists lead many chronic
pain rehabilitation programs. And, of course, psychiatrists have been
closely involved where pain, illness behavior, stress, depression, anxiety,
and substance abuse overlap. During the last decade, specialists from these
other disciplines have been seeking subspecialty training in pain medicine
with increasing regularity.
The range of practitioners declaring themselves as pain medicine
specialists is extraordinary; from clinics that provide largely or solely
cognitive-behavioral approaches to chronic pain through functional
restoration programs all the way to the type of clinic that offers nothing
more than injections of various sorts. “Interventional pain medicine” is a
term that has been coined for those techniques that involve minimally
invasive treatments and minor surgery as part of their application,
including neural blockade and implantable analgesic devices. Despite the
paucity of scientific evidence to guide pain practitioners, particularly,
evidence to support the use of many interventional modalities, many
techniques appear to have efficacy based on limited observational data and
have been adopted into widespread use. As practitioners, we are left to
choose among available treatment modalities, often with only anecdote
and personal experience to guide us in treating a group of desperate
patients with intractable pain who are willing to accept almost any
treatment, even those which remain unproven. There is no single practice
pattern that any pain specialist can point toward as the correct way to treat
patients with chronic pain. Training programs vary widely in the scope of
what they train practitioners to do. The best pain medicine practitioners
strike a reasonable balance between interventional and noninterventional
management. This practice pattern is sustainable, and those adopting a
balanced style of practice will be able to adapt to evolving scientific
evidence that appears in support of pain treatment regardless of the type of
treatment. A balance between treatment modalities also allows
practitioners to switch from one mode to another or incorporate multiple
treatment approaches simultaneously. Use of these interventional
modalities is just a small part of the armamentarium of the skilled pain
medicine practitioner.

5342
Pain Medicine as a Primary Medical Specialty
Dr. Bonica developed his multidisciplinary clinic with the understanding
that the expertise of several specialties was necessary to successfully
manage chronic pain. A detailed history of the intellectual background of
pain medicine and particularly Bonica’s work in the early development of
the field can be found in Baszanger’s 1998 book, Inventing Pain
Medicine.5
The rationale for a separate specialty in pain medicine involves the
documentation of many factors: public health need,6–8 a growing
consensus of pain treatment as a human right,9 ethical difficulties that are
at the heart of pain medicine practice,10,11 inadequate education3 and
knowledge12 and a rapidly growing scientific and practice base,13 and the
need to promote integrated pain medicine with primary care.14,15 The high
costs of inadequately managed pain reverberate in our society’s health care
crisis and are well documented. Emblematic of the same, it has been our
citizens, the victims of inadequate pain management, who have decried
this problem and demanded change through legislation at both a state and a
national level when organized medicine, itself beset by competition among
established specialties, cannot act. The rationale is scientific as well. Since
the publication of John Bonica’s first edition of The Management of Pain
in 1953, the problem of pain has challenged some of the best minds in
science and medicine. In 1965, Melzack and Wall’s16 seminal paper in
Science describing the gate theory of pain created a conceptual framework
resulting in a relative explosion of science in the physiology, molecular
biology, and pharmacology of acute pain and the epidemiology,
neurobiology, pathophysiology, genetics, and treatment of chronic pain
conditions and diseases at the levels of soma, spinal cord, and brain.
Today’s pain medicine physician is armed with a tremendous knowledge
base as a foundation for the myriad of effective medications, behavioral
therapies, physical therapies, neural blockades, neuromodulatory devices,
and cross-cultural complementary and alternative treatments such as
acupuncture and meditation. A growing number of pain medicine and
other specialists in organized medicine believe that longer training, either a
2-year fellowship or a separate 3-year residency, is needed to learn how,

5343
when, and in what combinations of these tools can be cost-effectively
utilized to competently treat patients with chronic pain, to establish
standards for training all physicians, and to lead the development of
clinical research and health policy.17 Although each traditional medical
specialty contributes to this knowledge base and skill set, their respective
specialists are not trained to manage the entirety of the spectrum of chronic
pain contributing to fragmentation not unification of care and failed public
health. Table 111.1 outlines the special skills contributed by traditional
specialties that converge to define the pain medicine specialist. This
specialized knowledge, education, training, and multidisciplinary nature
suggest that pain medicine’s evolution as a specialty is paralleling that of
other disciplines, such as emergency medicine or physical medicine and
rehabilitation. Knowledge and skills of the latter disciplines, initially
fragmented, later coalesced into primary medical specialties because of the
inability of multiple specialties to offer an integrated approach that would
best serve patients, medical science, and public health.

TABLE 111.1 Examples of Disease and Treatment Contributions to

Pain Medicine from Traditional Specialties
Illness/Disease Knowledge Medical Skill/Treatment
Specialty Contribution Contribution
Anesthesiology Acute pain Regional anesthesia (including
Chronic pain neurolytic)
Cancer pain Spinal anesthesia
Operative anesthesia
Neurology Peripheral neuropathy Assessment of neuropathic
Neuropathic pain pain
Central pain Neuropathic pain analgesia
Headache Headache medication
Neurosurgery Spine disease Implantable medication
Central pain pumps
Neurostimulation
Spine evaluation and surgery
Orthopedic surgery Low back pain Spine evaluation and surgery
Physical disability Joint surgery
Palliative care Cancer pain End-of-life symptom
management
Bioethics
Primary care Chronic diseases Chronic disease management
Biopsychosocial medicine

5344
 Psychiatry, behavioral Psychiatric comorbidity; Antidepressant analgesia
medicine stress, behavior and Behavioral rehabilitation
emotions Biofeedback and relaxation
Fibromyalgia Biopsychosocial formulation
Personality and coping Psychotherapies (dynamic,
cognitive behavioral, group,
family, hypnosis)
Psychiatric diagnosis
Psychological and
psychometric evaluation
Psychopharmacology
Radiologic medicine Diagnostic imaging
Procedure imaging
Radiotherapy
Rehabilitation medicine, Musculoskeletal medicine Physical therapy
physical therapy Myofascial pain Physical rehabilitation
Physical disability Transcutaneous electrical
nerve stimulation
Trigger point therapy
Rheumatology Joint diseases Joint injections
Fibromyalgia Peripheral nociceptive
analgesia (nonsteroidal anti-
inflammatory drugs)
Complementary and Acupuncture
alternative medicine Massage
Meditation
Tai chi

The momentum to establish standards for pain medicine as a specialty is

now global. For example, in 1998, the government of Australia formally
recognized pain medicine as a specialty and endorsed training and
credentialing requirements recommended by the newly formed Faculty of
Pain Medicine of the Australian and New Zealand College of
Anaesthetists.18 In 2007, the Section and Board of Anaesthesiology of the
European Union of Medical Specialists (UEMS) initiated the
establishment of the Multidisciplinary Joint Committee on Pain Medicine
of the UEMS, which has created a certification examination in pain
medicine (see further discussion of training in the European Union later in
this chapter). Also in 2007, the Ministry of Health of the People’s
Republic of China announced the designation of pain medicine as a
separate specialty and that there will be a Department of Pain Medicine in
all major hospitals in China (R. M. Gallagher and J.-S. Han, December

5345
2007, oral communication). In the United States, the momentum for
establishing residency training programs in pain medicine under a new
residency review committee has never gained momentum. The simple
rationale is that training for 1 year has proven to be inadequate, but the
status of pain medicine will remain as a subspecialty with just 1 year of
training until leaders in the field find a way to collaboratively improve the
depth and breadth of training. Similar to a cardiologist learning the science
and clinical practice related to the cardiovascular system, starting with
primary prevention of heart disease, by identification and early
intervention of risk, and primary and secondary treatment of actual heart
disease, the pain medicine specialist who will train in the future could
learn about the pain perception and modulation system, from the relatively
simple peripheral nociceptor to the system’s complex neurobehavioral
networks and about the pathophysiologies of this system.19,20

Training in Pain Medicine in Europe

In Europe, there is no systematic training in pain medicine for medical
students. The lack of obligatory training leads to later deficiencies in
clinical care. Some countries (e.g., Germany) have made efforts in
establishing a core curriculum for medical students. However, the
worldwide need for a thorough basic education in pain medicine is
underestimated by most health care officials.
The postgraduate training varies widely within Europe. This led to
guidelines for anesthesiologist specialist training in pain medicine.21 In
these guidelines, approved by the UEMS, pain medicine is considered to
be an area of expertise in anesthesiology. However, simultaneously, it is
mentioned that pain medicine is not claimed for anesthesiology alone. It is
clearly stated that pain medicine is included in anesthesia specialist
training. However, an additional qualification following basic anesthesia
training is recommended. The multidisciplinary approach to pain is
mentioned, and an initiative to set up a multidisciplinary joint committee
on pain medicine within the UEMS has begun.
The proposed duration of pain medicine training is 3 months during the
5 years of basic anesthetic training required in the European Union. In

5346
contrast to this relation representing only 5% of the total time of training, it
is recommended to occupy a minimum of 10% of the multiple-choice
questions on the European Society of Anaesthesiology’s European
Diploma in Anaesthesiology and Intensive Care.
Some years ago, the Scandinavian Society of Anaesthesiology and
Intensive Care Medicine established the Nordic education in advanced
pain medicine. The clinical part lasts at least 3 months. The education
includes, and this is unique in Europe, a scientific part.22
In April 2007, the Royal College of Anaesthetists (United Kingdom)
established a faculty of pain medicine and stressed this as a major way
point in the last 50 years.23 However, the question is raised: Should pain
medicine strive to be a “stand-alone speciality,” or should it be linked to
parent specialties like anesthesiology? Additionally, is education also
required for the public and the patients? Both the British and the Irish
curriculum in pain medicine require similar training and examination. The
candidate has to complete a total of 6 months training in pain medicine
before ending up with a 2-day written and oral examination with review of
actual clinical cases and a practical examination.
As early as 1992, the German Society of Anaesthesiology started a
curriculum and specialist training in pain medicine. This included a 2-
week theoretical course and a 1-year practical training requirement in a
pain clinic. From this first example, a specialty open for all clinical
disciplines has been developed. Since 1996, a specialty called “specialized
pain therapy” has been established by the German Medical Assembly. A
curriculum has been developed by the German Pain Society and approved
by the German Medical Assembly. Similar to the Society of Anaesthetists,
the specialization demands 1 year of clinical training in a certified
institution and an 80-hour theoretical course. Additionally, to maintain
specialty certification, physicians must attend multidisciplinary pain
conferences regularly, where patients are presented and discussed between
several disciplines, including at least one psychological discipline. In
2008, Austria introduced a similar specialty, and the German training is
approved by the Austrian Medical Assembly.
The dramatic effect of a thorough education and programmatic work has
been demonstrated in Catalonia in Spain within a project sponsored by the

5347
World Health Organization. Symptom control and patient satisfaction were
both improved, and a striking cost savings of many million Euros per year
has been demonstrated as compared to the rest of Spain.24 Europe has
lagged behind the United States in developing formal training for pain
medicine specialists.
In 2016, the European Pain Federation EFIC developed a curriculum,
predominantly based on the pain curriculum of the Faculty of Pain
Medicine of the Australian and New Zealand College of Anaesthetists.
The knowledge of the curriculum, pain assessment, and treatment skills are
evaluated by a two-part examination: the European Diploma in Pain
Medicine (EDPM). The examination is open to all qualified doctors who
see and treat patients with pain who have appropriate clinical experience in
pain assessment and treatment. The diploma aims to show that the fellow
has a firm grounding in the basic skills and knowledge needed to assess
and manage the many patients whose pain requires attention in all types of
clinical scenario. The EDPM assesses the general knowledge of
multidisciplinary pain management. Some countries in Europe have also
approved the examination of the World Institute of Pain (WIP) to become
Fellow in Interventional Pain Practice (FIPP) as an evaluation of the skills
to select and perform interventional pain management techniques.

Training and Credentialing in Interventional Pain

Medicine
In our rapidly changing world of modern health care, new technologies are
appearing at a dizzying rate. Many of these new treatments require
physicians to acquire detailed new knowledge and technical skills. The
introduction of new techniques typically extends from centers in the public
or private sector, where the ideas are conceived and tested in a limited
realm among innovators. From there, anecdote can often take over, and
many techniques in pain medicine have blossomed into widespread use
with nothing more than word-of-mouth to propagate their use. The use of
pulsed radiofrequency treatment for treatment of chronic pain after
herniorrhaphy is one such example where clinical application has preceded
detailed clinical testing.25

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 In the United States and Europe, industry often leads innovation by
testing and leading the introduction of new devices. When the innovation
appears to have merit in limited trials, many devices have been introduced
to the market with approval through the U.S. Food and Drug
Administration’s (FDA) 510K “substantially similar device” process with
little or no data regarding efficacy. Once on the market, the means by
which practitioners decide to adopt new technologies, the speed of
progression of these new techniques, and—of great importance—the
means by which practitioners gain enough expertise to introduce new
techniques into their own practices, are all highly variable and seemingly
without any rational or consistent approach.
Interventional pain medicine is evolving as a distinct discipline that
requires detailed new knowledge and expertise. Familiarity with
radiographic anatomy for the conduct of image-guided injection and the
minor surgical skills needed to place implanted devices such as spinal cord
stimulators and implanted drug delivery systems are just a few of the
techniques that practitioners must master. As we set out to introduce new
interventional techniques to our own pain practices, we must assure that
we have been properly trained to conduct these techniques to ensure safety
and success.
Adequate exposure during the fellowship-training period to these newer
treatment alternatives is necessary to assure appropriate application and
optimize patient outcomes. Although we do not have scientific data that
define the average minimum level of experience that will be necessary to
achieve competence, especially for complex procedures that are associated
with significant risks, logic dictates that there are a minimum number of
these procedures that trainees should be exposed to during a fellowship.
The ACGME has established requirements for average minimal numbers
of epidural, spinal, and peripheral nerve blocks necessary for accreditation
of anesthesiology residency programs. Other medical subspecialties also
require a minimum number of specified procedures to achieve and
maintain competence: Subspecialty training in gastroenterology has a
requirement of performing a minimum of 100
esophagogastroduodenoscopies and 100 colonoscopies with polyp
removal26 during formal training, and subspecialty training in

5349
cardiovascular disease requires 100 cardiac catheterizations to demonstrate
minimum proficiency.27 Indeed, in 2017, the ACGME’s RRC for
Anesthesiology has accepted revised program requirements for pain
medicine training programs that specify minimum exposure of trainees for
various techniques. For those techniques that are now widely accepted as a
core part of pain practice, we must assure that our trainees gain enough
experience to conduct these procedures independently. One key element of
the ACGME deliberations about unified pain training is to acknowledge
that not all pain fellows will have experience in the wide variety of
interventional techniques. Rather, it is hoped that these fellows will gain
an understanding of all available options for patients with pain and yet
demonstrate and have competence documented in only those techniques
for which formal training is made available during fellowship training.
It is difficult to define the techniques that are core for a pain
practitioner, but it does seem that detailed knowledge of radiographic
anatomy of the spine and the minor surgical skills required to implant
spinal cord stimulators and place permanent spinal drug delivery systems
are among those skills most practicing pain physicians would expect a new
graduate from a pain fellowship to emerge with. New techniques are
appearing at a staggering rate, and we cannot rely on pain fellowship
programs to provide all of the technical training that is needed. Stronger
standards for minimal training following fellowship are also urgently
needed. Some pain practitioners believe that all too many of their
colleagues find it perfectly acceptable to attend a brief weekend course and
then introduce a highly technical new treatment into practice without
additional study, training, or oversight.28 The recent proliferation of new
approaches to minimally invasive treatment of spinal pain and spinal cord
stimulation all require unique knowledge and skills to be used safely and
effectively. Practitioners themselves must take the lead in obtaining
adequate training before proceeding with any new and unfamiliar
technique. The weekend workshop is just a start, often a good start—the
best will give practitioners a detailed understanding of anatomy;
pathophysiology of disease related to the use of the new technique; patient
selection; conduct of the procedure; outcomes; and avoidance,
management, and recognition of complications. Here, we would like to

5350
suggest a method for practitioners29 (Table 111.2): (1) study the new
technique, the published literature, and gain a detailed knowledge of all
aspects of the technique; (2) attend a workshop, preferably a hands-on
cadaver-based workshop that allows introduction to the technique in as
realistic a setting that can be assembled; (3) plan adequate time for your
initial procedures; (4) get help at the bedside during initial conduct of new
procedures—perhaps another experienced practitioner at your institution,
an invited expert to assist, or team up with a colleague in a related
discipline; (5) inform your patients that you are introducing a new
technique and include this discussion as part of the informed consent
process; and (6) examine your outcomes carefully in the initial stages of
using any new technique and compare them with those of your colleagues
and the published literature.

TABLE 111.2 Suggested Training and Experience When

Introducing a New Technique in to Clinical Practice
1. Study the new technique, the published literature, and gain a detailed knowledge of all aspects
of the technique.
2. Attend a workshop, preferably a hands-on cadaver-based workshop that allows introduction to
the technique in as realistic a setting that can be assembled.
3. Plan adequate time for your initial procedures.
4. Get help at the bedside during initial conduct of new procedures—perhaps another
experienced practitioner at your institution, an invited expert to assist, or team up with a
colleague in a related discipline.
5. Inform your patients that you are introducing a new technique and include this discussion as
part of the informed consent process.
6. Examine your outcomes carefully in the initial stages of using any new technique and
compare them with those of your colleagues and the published literature.

Conclusion
The field of evidence-based medicine has emerged as a new paradigm to
guide practicing physicians. This field endeavors to educate practitioners
about how to frame specific questions based on the clinical problems they
are faced with every day. They then venture to the published scientific
literature with focused questions about prevention, diagnosis, and
treatment of a specific clinical condition. Many evidence-based medicine
centers offer concise and periodically updated summaries about specific

5351
clinical conditions. The idea is to get the best information available to the
practicing clinician. It describes the best available evidence, and if there is
no good evidence, it says so. In pain medicine, we are faced with an
expanding array of treatment options that strikes us as logical
developments that should provide pain relief for our patients. However,
there is a dearth of clinical evidence to guide rational choice and
application of the majority of these emerging treatments. So how are we to
decide when to apply them?
Merrill30 presented a detailed analysis of the current state of evidence
guiding the use of interventional treatments in the field of pain medicine.
He points out the frequent flaws in existing studies (largely the lack of
valid comparators, such as no treatment) and concludes that “the practice
of invasive pain medicine teeters at a particularly critical juncture . . .
crippled by a lack of vigorous self-evaluation of its role in the treatment of
chronic pain.” Merrill30 goes on to detail the means by which we, as
scientists and clinicians, can proceed to build a better body of evidence for
the treatments we are using. But the field of pain medicine is young and
early in development, and it is perhaps unreasonable to expect an
accumulation of randomized clinical trials just yet.
New treatments evolve slowly in clinical medicine. Applying the
scientific method in clinical medicine begins with an observation. Perhaps
a chance observation that a certain drug typically used for another purpose
provides analgesia to a given patient. If the drug is readily available, a
clinician may choose to try treatment on other patients with similar
presentations. If an academic sort, the clinician may choose to report the
limited success in a case series. Case series are a valuable beginning: the
very beginning of emerging new ideas. If the problem is uniform and
prevalent enough, the new treatment may gain the attention of
investigators willing to assemble a randomized clinical trial. All too often,
sound treatments are never tested for lack of interest or funding. Those that
are tested tend to be those under patent where a manufacturer proceeds
with these large endeavors understandably in hope of financial return in
the event the treatment proves useful. Patients who are suffering from
severe and intractable pain are desperate, and they can easily be convinced
that desperate measures, however new or unproven, are warranted.

5352
 How, then, are we to proceed? Our patients are begging for us to try
anything that offers a glimmer of hope in reducing their pain, and we as
scientists embrace the rigor of the scientific method and want desperately
to do what is best for our patients. We have treatment after treatment that
makes logical sense and shows early promise in case series and
observational studies but little data that support an evidence-based
approach to practice. The evidence-based medicine movement gives little
guidance to practitioners whose tools are still under development. They
simply remind us that no evidence regarding many of our techniques
exists. Without declaring a moratorium on all of interventional pain,
Merrill30 offers the individual practitioner advice: Monitor your own
outcomes using valid measures, be more reflective and systematic in
studying your own outcomes and patterns of care, and provide this
information to your patients as part of the decision-making process. As
pain practitioners, we have an expanding range of treatment options
available to us, few with convincing evidence of efficacy superior to
alternate treatments. We must evaluate each patient and use the limited
evidence available to us today to guide compassionate and rational, if not
evidence-based, use of therapy for our desperate patients.

ACKNOWLEDGMENTS
We would like to thank Michael Zenz, Rollin M. Gallagher, and David L.
Brown, who contributed to this chapter for Bonica’s Management of Pain,
fourth edition. We have built on the previous edition’s chapter to create
this updated chapter.

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21. Cunningham AJ, Knape JT, Adriaensena H, et al. Guidelines for anaesthesiologist specialist
training in pain medicine. Section and Board of Anesthesiology, European Union of Medical
Specialists. Eur J Anaesth 2007;24:568–570.
22. Scandinavian Society of Anaesthesiology and Intensive Care Medicine. SSAI’s Nordic
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of the Standing Advisory Committee for Socio-Health Affairs, Department of Health,
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2012;37:340–343.
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C H A P T E R 11 2
Emergencies in the Pain Clinic
CHRISTOPHER GILLIGAN, MILAN P. STOJANOVIC, RAMSEY
SABA,
and JAMES P. RATHMELL

This chapter seeks to provide the pain management specialist with an

overview of emergencies and complications that may occur in the course
of caring for patients with acute and chronic pain. Throughout this review,
we will also emphasize strategies for decreasing risk, specifically,
strategies for identifying specific risks and considering alternatives,
understanding rare event analysis, and maintaining a comprehensive view
of the patient when prescribing specialty specific interventions. A prudent
first step for practitioners who will be managing emergencies related to
pain therapies is to understand the incidence of each of these emergencies.
However, because rates have been relatively low for serious
complications, and because minor complications frequently go unreported,
measuring the true incidence of most complications is not feasible.

The American Society of Anesthesiologists Closed

Claims Project
In the United States, the American Society of Anesthesiologists Closed
Claims Project offers a close look at serious adverse events secondary to
pain management interventions that lead to malpractice claims, but no
incidence can be calculated due to the lack of any knowledge regarding the
overall frequency with which the interventions are performed. We can,
however, make educated changes to our practice by evaluating trends in
these closed claims.
A review of 1,037 total pain medicine malpractice claims of the
database between 1980 and 2012 showed that most claims were related to

5356
lumbar nonneurolytic injections (n = 273). Other claims included cervical
nonneurolytic injections (n = 211); device implantation, management, or
removal (n = 146); and medication management (n = 115). Looking just at
the claims between the years 2000 and 2012 (n = 505), we find that most
claims have trended toward cervical nonneurolytic injections (Table
112.1). Furthermore, the overall percentage of malpractice claims for pain
medicine has increased from 3% of all anesthesia malpractice claims
between 1980 and 1989 to 18% of all anesthesia malpractice claims
between 2000 and 2012 as reviewed from the American Society of
Anesthesiologists Closed Claims Project database. Outcomes in pain
medicine claims have also grown increasingly more severe in nature over
the years. Death and permanent disability increased from 21% of pain
medicine claims in the 1980s to 55% of claims in the 2000s.1
Nerve damage and pneumothorax were the most common adverse
events leading to claims in interventional pain management claims (Fig.
112.1). Serious adverse events leading to brain damage or death occurred
at a far lower rate than that seen in surgical and obstetric anesthesia claims.
A closer analysis of the subset of claims associated with epidural steroid
injections (ESIs) revealed that death and brain damage occurred only when
local anesthetic or opioid (or both) were administered in conjunction with
the steroid (Fig. 112.2). This likely reflects unintended delivery of local
anesthetic or opioid to the subarachnoid space or simply the predictable
effects of neuraxial opioids; resultant high spinal anesthesia or neuraxial
effects of opioid could both have led to respiratory compromise and
underscores the need for close observation following neuraxial
administration of local anesthetic or opioid. Not infrequently, claims
resulted from the maintenance of spinal drug delivery systems (20/276
claims or 7%); these claims often stemmed from refilling of implanted
drug reservoirs with potent opioid by nonphysician personnel in the
outpatient or home care settings.

TABLE 112.1 Specific Procedures Used for the Treatment of

Chronic Pain within the American Society of Anesthesiologists
Closed Claims Project that Led to Malpractice Claims (n = 505)
Claims 2000–2012

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 Procedure n %
Cervical nonneurolytic injections 134 27
Lumbar nonneurolytic injections 87 17
Medication management 87 17
Devices 83 16
Other nonneurolytic injections 43 9
Neurolytic procedures 33 7
Other procedures 38 8
Reprinted with permission from Pollak KA, Stephens LS, Posner KP, et al. Trends in pain medicine
liability. Anesthesiology 2015;123(5):1133–1141.

FIGURE 112.1 Primary outcomes within the American Society of Anesthesiologists Closed
Claims Project in chronic pain management claims (yellow bars) versus surgical/obstetric claims
(green bars). *P < 0.05. (Reprinted with permission from Fitzgibbon DR, Posner KL, Domino KB,
et al; American Society of Anesthesiologists. Chronic pain management: American Society of
Anesthesiologists Closed Claims Project. Anesthesiology 2004;100[1]:98–105.)

FIGURE 112.2 Most common outcomes within the American Society of Anesthesiologists
Closed Claims Project in those claims following epidural steroid injection. Yellow bars represent
injections with steroids only. Green bars indicate injections in which local anesthetic or opioid (or
both) were added to the steroid. *P < 0.05 between proportion of injection group with that outcome.
(Reprinted with permission from Fitzgibbon DR, Posner KL, Domino KB, et al; American Society
of Anesthesiologists. Chronic pain management: American Society of Anesthesiologists Closed
Claims Project. Anesthesiology 2004;100[1]:98–105.)

5358
Bleeding Complications
Spinal hematomas have been described in autopsies since 1682 but not as a
clinical diagnosis until 1867.2 Within one decade of August Bier’s
discovery of spinal anesthesia, the first known epidural hematoma as a
complication of spinal anesthesia occurred in a 36-year-old male following
unsuccessful neuraxial blockade for excision of a pilonidal cyst.3 In that
case, repeated lumbar puncture revealed blood-tinged cerebrospinal fluid
(CSF), and the patient subsequently developed paresthesias and weakness
in both lower extremities. The introduction of heparin in 1937 and
warfarin in 1941 introduced the possibility of anticoagulation contributing
to epidural hematoma formation. Epidural hematoma is a rare but
potentially catastrophic complication of spinal or epidural anesthesia or
injections. Because the spinal column is an enclosed space, hematoma
formation can cause compression and ischemia of neural structures.
Bleeding may result from injury to the abundant epidural veins or may be
arterial. A retrospective study of central neuraxial blocks in Sweden from
1990 to 1999 identified 33 spinal hematomas, during a period when
approximately 1,260,000 spinal blocks and 450,000 epidural blocks were
administered. In that study, the incidence of spinal hematoma was 1 in
200,000 after obstetric epidural blockade and 1 in 3,600 among female
patients undergoing knee arthroplasty.4 At a single teaching hospital in
Australia, data were collected prospectively over a 16-year period for all
epidural catheters placed for postoperative analgesia. During that period,
8,210 epidural catheters were inserted, and 2 spinal hematomas (1:4,105)
and 6 epidural abscesses (1:1,368) were diagnosed.5 In rare instances,
spinal epidural hematoma has developed following chiropractic
manipulation and acupuncture therapy.6,7 Factors that determine whether
epidural hematoma results in injury to neural structures include the
location in the spinal column (the level of the cauda equina is relatively
resistant to injury, whereas the cervical spinal cord is not), and the rate at
which the blood accumulates. Tarlov8 demonstrated in dogs that spinal
cord injury due to spinal epidural hematoma depends on both the amount
of pressure exerted on the spinal cord and the duration of that pressure
elevation. Interestingly, some epidural hematomas cause significant injury

5359
despite the fact that their volume is significantly less than that typically
used during epidural blood patch placement. Vertebral column neoplasms
and vascular malformations are also risk factors. Patients who have an
underlying coagulopathy or are being anticoagulated with warfarin,
intravenous (IV) heparin, subcutaneous low molecular weight heparin,
platelet-inhibiting medications such as clopidogrel or ticlopidine, platelet
glycoprotein IIb/IIIa receptor inhibitors, or fibrinolytic agents are at
elevated risk of spinal hematoma formation. It should also be noted that
with the growing number of patients on novel anticoagulation agents,
including but not limited to, apixaban, dabigatran, rivaroxaban, prasugrel,
and ticagrelor, a careful consideration of guidelines and practice advisories
are necessary prior to any neuraxial procedures. The incidence of
spontaneous spinal epidural hematoma estimated by Holtås et al.9 was 0.1
per 100,000 people, and less than 1% of those with spinal hematomas had
their spinal epidural space occupied by lesions. The etiology of these
hematomas was unsurprisingly related to coagulopathies, vascular
malformations, neoplasms, infections, minor vertebral traumas, and
idiopathic causes.10 In addition, garlic has been shown to inhibit platelet
aggregation and has been linked in one case to the development of a
spontaneous epidural hematoma. Ginkgo biloba inhibits platelet-activating
factor and has been linked to several cases of spontaneous intracranial
bleeding, and ginseng inhibits platelet aggregation and prolongs both
thrombin time and activated partial thromboplastin time, although the
clinical significance of these findings remain unclear.11–13
Timely diagnosis of spinal epidural hematoma is critical but, in many
cases, will be challenging. Many patients have few complaints initially,
commonly developing progressively worsening back pain as the hematoma
expands with or without the immediate or delayed appearance of focal
neurologic deficits. A progressive neurologic deficit may develop over a
variable interval and with variable severity. Typically, neurologic deficits
evolve over the course of several hours, but in some instances, they may
develop over several days. In some instances, neurologic deficit rather than
pain may be the presenting sign. Physical findings of myelopathy, or the
development of the Brown-Sequard syndrome, should be recognized as
indicative of spinal cord compression and should prompt emergent

5360
diagnostic evaluation and treatment.14 Intractable leg pain and cauda
equina syndrome may develop as well. Urinary retention may precede
urinary incontinence. When a spinal epidural hematoma is suspected, a
thorough neurologic examination is mandatory. This examination should
include evaluation of anal sphincter tone and direct examination in efforts
to detect loss of perineal sensation. Furthermore, serial examinations
should be performed at short intervals. Findings on physical examination
will be variable depending on the level of the lesion. Unilateral or bilateral
weakness and/or paresthesias may be present. Hyper- or hyporeflexia may
also be present. Depending on the clinical context, the differential
diagnosis may include spinal epidural abscess. Urgent laboratory studies
should include a complete blood count with platelets as well as a
prothrombin time and activated partial thromboplastin time. In addition, a
blood bank sample should be sent for type and cross-match in preparation
for surgery as well as in cases where fresh frozen plasma may be needed to
reverse coagulopathies.
Magnetic resonance imaging (MRI) is the preferred radiologic study for
diagnosis of spinal epidural hematoma. On sagittal reconstructed
computed tomography (CT) or MR images, a spinal epidural hematoma
typically appears as a biconvex mass dorsal to the thecal sac, with tapering
cephalad and caudal margins (Fig. 112.3). Associated spinal cord edema
may also be seen. Acute hemorrhage is characterized by a marked decrease
in signal intensity on T2-weighted images. Subacute hematoma is
characterized by increased signal intensity on both T1- and T2-weighted
images.15 The dura matter appears as a low-signal curvilinear structure
separating the hematoma from the spinal cord on T2-weighted gradient
echo sequences. In one retrospective study of 17 patients with acute spinal
epidural hematoma, 10 patients’ T1-weighted images showed isointensity
to the spinal cord, and in 7 patients, the hematomas were slightly
hyperintense. T2-weighted images showed hyperintensity with areas of
hypointensity. Other MRI findings included hematomas showing direct
contiguity with the adjacent osseous spine in 13 patients. Posterolateral
location of the hematomas was noted in 13 patients. Additional findings
were capping of the epidural fat, compression of the epidural fat and
ligamentum flavum, and compression of the thecal sac and/or cord.16 MRI

5361
will also help to identify associated spinal cord tumors or arteriovenous
malformations. For patients who cannot undergo MRI scanning or in cases
where MRI scanning is not immediately available, CT, with or without
myelography, is the study of choice. A spinal epidural hematoma appears
as a biconcave dorsal mass typically extending over at least two vertebral
levels (see Fig. 112.3).17 Lumbar puncture does not add to the diagnosis
and may worsen the patient’s condition in some instances.

FIGURE 112.3 Magnetic resonance imaging (MRI) of the lumbosacral spine demonstrating a
lumbar epidural hematoma. Axial (A) and sagittal (B) reconstructed T2-weighted MRIs
demonstrating a biconvex mass dorsal to the thecal sac extending from the cervicothoracic junction
to the low thoracic area, with tapering cephalad and caudad margins, the typical appearance of an
epidural hematoma.

When spinal epidural hematoma is entertained as a diagnosis, urgent

neurosurgical consultation should be obtained. In a retrospective study of
30 patients who were treated for spinal epidural hematoma between 1979
and 1993, rapidity of surgical decompression of the spinal cord correlated
with neurologic outcome.16 Patients who were taken to surgery within 12
hours of symptom onset fared significantly better than those whose surgery
was delayed beyond 12 hours. In this series, the patients’ preoperative
neurologic status was also predictive of outcome. Of note, in a series of 30
patients, of 8 patients who had complete loss of neurologic function
(Frankel grade A), 6 improved with surgical decompression, and 2 of these
regained normal function.12 Emergent surgical evacuation remains the
standard of care and treatment of choice for spinal epidural hematoma. In

5362
some instances, spinal epidural hematomas have been successfully
conservatively managed, typically in patients whose neurologic
examination was spontaneously, steadily improving.18

Infectious Complications
Infectious complications may ensue following either peripheral or central
neuraxial blockade, although the latter is more likely to lead to
catastrophic sequelae such as meningitis or compression of neural
structures. Both superficial and deep infections have been reported
following epidural injections, facet joint injections, and trigger point
injections. In the case of indwelling catheters, the risk of infection
increases with increased duration of catheter therapy. One systematic
review examining 4,628 cancer patients with indwelling catheters left in
place for 7 days or more found that the incidence of deep infection was 1
per 2,391 days of treatment, or 0.4 per 1,000 catheter treatment days. The
average catheter duration for these patients was shown to be 74 days with
a deep infection rate reaching 2.8%. Four out of 57 of the patients with
deep infections related to their indwelling catheters died from these
infection complications.19 When comparing infection rates between cancer
and noncancer patients, one study retrospectively examined 131 patients
(80% cancer patients) and found no difference in infection rates of spinal
cord stimulator and intrathecal drug delivery systems.20 In the case of
implanted spinal cord stimulators and intrathecal drug pumps, a review of
four prospective trials found 36 infections in 35 patients out of a total of
700 patients who underwent implantation. The overall infection rate was
5% with 57% to 80% of the infections in the trials involving the pump
pocket, 13% to 33% involving the lumbar site, and 0% to 14% leading to
meningitis.21 One study showed that a more skilled/experience operator
had a lower infection rate (1.8%) compared to the less skilled/experienced
(13%).22 All patients undergoing interventional therapies for pain
treatment should be given explicit written postprocedural guidelines that
include a clear description of the signs and symptoms that may herald an
infection and a clear process for contacting pain clinic personnel on an
urgent basis if such signs and symptoms develop.

5363
 The source of the pathogen may be either external, as in the case of
contaminated equipment or breaches in sterile technique, or internal, in the
case of patients with local or systemic infections such as skin and soft
tissue infections or bacteremia. It is not surprising then that occlusive
postsurgical dressings and perioperative antibiotics have been shown to
decrease the risk of infections.23 Risk factors for infection include
diabetes, alcoholism, smoking, and immunosuppression. Similarly,
infections in the epidural space may spread to other areas via
hematogenous spread or local extension. Pathogens include skin flora such
as Staphylococcus aureus and Staphylococcus epidermidis. In patients
with implanted spinal catheters or devices, the incidence of methicillin-
resistant S. aureus epidural infection is particularly high. Injury to the
neural structures may occur due to direct compression by an abscess or due
to ischemia caused by septic thrombophlebitis.
Initially, the patient with an evolving epidural abscess typically presents
with back pain at the affected level of the spine. Subsequently, they may
develop radicular pain corresponding to the involved level. They may then
progress to development of motor and sensory deficits accompanied by
bowel and bladder dysfunction and finally to frank paralysis. Back pain
will be present in roughly three-quarters of patients, fever in almost half,
and neurologic deficits in about one-third. Thus, the classic triad of back
pain, fever, and neurologic deficit is seen in only a minority of patients.24
Both the duration of symptoms prior to presentation and the rate of
progression of symptoms can be highly variable. Spinal epidural abscesses
typically extend over three to four vertebral levels; however, in rare
instances, they may involve the whole spine. Laboratory studies should
include a complete blood count with differential as about two-thirds of
patients will have leukocytosis. Erythrocyte sedimentation rate and C-
reactive protein are almost always elevated, although neither of these tests
is specific. Blood cultures should be sent prior to the administration of
antibiotics and approximately 60% of patients will be bacteremic. When
lumbar puncture is performed, CSF analysis shows elevated protein and
pleocytosis in three-quarters of patients. Gram staining and culture of CSF
are negative in the majority of patients. Lumbar puncture adds little to the
diagnosis and entails risk of causing meningitis if the needle traverses the

5364
epidural abscess en route to the thecal space; CSF should be analyzed if
myelography is undertaken.
MRI with IV gadolinium is the study of choice to evaluate possible
epidural abscess (Fig. 112.4). MRI is highly sensitive for diagnosing
epidural abscess and allows evaluation of the dimensions of the abscess
which facilitates surgical planning. If MRI is contraindicated or is not
readily available, CT myelography is also quite sensitive but is more
invasive. Plain x-rays or CT scan of the spine without myelography may
demonstrate diminished disk space and/or bony destruction suggestive of
discitis and osteomyelitis. These conditions coexist with epidural abscess
in up to 80% of cases. Urgent surgical drainage accompanied by
administration of systemic antibiotics is the standard of care for epidural
abscesses.25 In rare cases, percutaneous drainage with systemic antibiotics
or antibiotic treatment in the absence of surgery may be undertaken.24

5365
FIGURE 112.4 Magnetic resonance imaging of the lumbosacral spine demonstrating epidural
abscess. This is a 64-year-old who presented with worsening axial low back pain 2 weeks following
lumbar epidural injection of steroid for treatment of acute radicular pain. Axial (A) and sagittal (B)
T1-weighted images. Axial (C) and sagittal (D) T2-weighted images. Axial (E) and sagittal (F) T1-
weighted images following intravenous administration of gadolinium. These findings are
compatible with diskitis/osteomyelitis at L2–L3, with enhancement of the anterior epidural space
and a focus of high T2 and low T1 signal in the left anterior epidural space consistent with epidural
abscess.

Superficial infections typically present with local erythema, pain,

5366
swelling, and, in some cases, purulent discharge. In some instances,
superficial infections associated with catheters can be managed with local
drainage and antibiotics without removing the catheter.26 Some cases of
superficial infections and pocket site infections following implantations of
spinal cord stimulators and intrathecal drug pumps have been successfully
managed using oral and parenteral antibiotics that correspond to
antimicrobial sensitivities on the basis of wound cultures, although the
implanted device has been left in place.27,28 However, as other authors
have noted, device-related infections are rarely completely eradicated
without removal of the device in question.21 This observation mirrors the
extensive experience with infected cardiac pacemakers.29 In all cases, a
high degree of vigilance must be maintained to the possibility that a
device-related superficial or pocket infection may spread to the neuraxis
with catastrophic results. In the event that signs of infection such as
erythema, swelling, fluctuance, or tenderness progress along the course of
an implanted lead or catheter, the device with all associated hardware
should be surgically removed on an urgent basis. Similarly, urgent device
removal should be undertaken if the patient displays signs of systemic
infection such as fever or chills, or signs of possible meningitis such as
fever, neck pain and stiffness, severe headache, or altered mental status. At
the time of surgery, separately labeled wound cultures should be sent from
all surgical sites, and all surgical sites should be extensively irrigated. As
with spinal epidural hematoma, the patient’s preoperative neurologic
function is the best predictor of final neurologic outcome.30 For any
patient where there is a significant concern for systemic infection or
meningitis, antibiotics should be administered immediately and should not
be delayed until cultures can be obtained. Empiric antibiotic coverage
should provide coverage of Staphylococcus species, preferably with
vancomycin to ensure coverage of methicillin-resistant S. aureus,
Streptococci species, and should also provide coverage of gram-negative
microbes with a third- or fourth-generation cephalosporin (such as
cefepime or ceftriaxone) or equivalent. When the etiologic agent has been
identified, antibiotics should be directed toward the specific pathogen.
Five percent of patients with spinal epidural abscesses die secondary to
sepsis or other infectious complications signifying the importance of early

5367
intervention.24

Local Anesthetic Systemic Toxicity

Lidocaine and bupivacaine are amide local anesthetics which are widely
used in interventional pain management procedures due to their relative
safety. Lidocaine is of relatively lower potency and has a rapid onset of
action and an intermediate duration of action. Nonetheless, the potential
for lidocaine associated systemic toxicity due to excessive dose,
inadvertent intravascular administration, or unanticipated rapid absorption
is well recognized. Bupivacaine is of higher potency but has a slower onset
and prolonged duration of action. Local anesthetics, including lidocaine
and bupivacaine, bind sodium channels and inhibit the sodium
permeability that underlies action potentials in both neurons and cardiac
myocytes. Local anesthetic inhibition of sodium permeability increases
with repeated depolarization. In addition to binding sodium channels, local
anesthetics will bind potassium and calcium channels as well as N-methyl-
D-aspartate receptors, β-adrenergic receptors, and nicotinic acetylcholine
receptors. Indeed, local anesthetic toxicity may be mediated in part
through binding to these channels and receptors.31–33 In general, the
anesthetic potency of a local anesthetic correlates with its central nervous
system (CNS) toxicity. Local anesthetics appear to cause cardiac toxicity
through several different mechanisms including inhibition of calcium and
potassium channels and inhibition of β-adrenergic receptors and
epinephrine stimulated cAMP formation. Local anesthetics prolong cardiac
conduction in a dose-dependent fashion. With increasing serum
concentration, bupivacaine provokes QT prolongation, ventricular
tachycardia, and ventricular fibrillation. Risk factors for the development
of local anesthetic toxicity include the extremes of age, end-organ
dysfunction (hepatic, renal, and cardiac), and pregnancy. The threshold
dose of local anesthetic required to provoke seizures is affected by the
route and rate of injection, the rate of increase of serum drug
concentration, the presence of acidosis, and whether the patient is awake
or anesthetized. Local anesthetic toxicity may result from systemic
absorption of excessive doses following local infiltration; however,

5368
toxicity more commonly occurs due to inadvertent intravascular injection.
Intra-arterial injection poses a greater risk of CNS and cardiovascular
toxicity than IV injection because, in the latter case, passage through the
lung allows for some clearance of the drug. In the case of intra-arterial
injection, doses as small as 2.5 mg of bupivacaine or 15 mg of lidocaine
have resulted in seizures when injected into the carotid or vertebral
arteries, and this is felt to result from direct delivery of the local anesthetic
to the brain.34,35
In the event of lidocaine toxicity, CNS symptoms typically precede
cardiovascular symptoms.36 CNS symptoms are initially characterized by
inhibitory neuronal blockade leading to excitatory manifestations such as
perioral numbness, a metallic taste, tinnitus, restlessness, confusion, a
sense of impending doom, visual disturbances that are most commonly
described as oscillations of objects in the visual fields, shivers, tremors,
and tonic-clonic seizures (Fig. 112.5). Sympathetic stimulation is also
observed during this phase, with resultant tachycardia and hypertension.37
In patients who are receiving procedural sedation with benzodiazepines or
other sedatives, the excitatory phase of local anesthetic toxicity may not be
apparent. The excitatory phase is followed in episodes of severe toxicity
by a depressed phase characterized by coma and respiratory arrest.
Cardiovascular toxicity develops at higher serum levels and may include
profound bradycardia, arrhythmias, contractile dysfunction, and asystole.31
In the case of bupivacaine, doses that are insufficient to provoke seizures
will provoke cardiac arrhythmias.38

FIGURE 112.5 Relationship between plasma concentration of lidocaine and the development of
signs and symptoms of local anesthetic toxicity.

Treatment of local anesthetic–induced seizures focuses on maintaining

5369
the airway and oxygenation. The injection or infusion of local anesthetic
must be stopped immediately. Lorazepam, midazolam, thiopental, or
propofol may be used to terminate the seizure. Cardiovascular depression
with resultant hypotension due to local anesthetic toxicity should be
treated with IV crystalloids and vasopressors such as norepinephrine, or
phenylephrine. In the event of severe contractile dysfunction, epinephrine
should be administered. If cardiac arrest occurs, advanced cardiac life
support (ACLS) protocol should be pursued, although if epinephrine is
used, small initial doses (≤1 μg/kg) are preferred and vasopressin is not
recommended. Successful resuscitation following cardiac arrest due to
bupivacaine toxicity has included the administration of IV lipid
emulsion.39,40 A 20% lipid emulsion may be administered as a 1.5 mL/kg
bolus followed by a 0.25 mL/kg/min infusion for 30 to 60 minutes. A
repeat bolus is often administered for persistent cardiovascular collapse. It
should be noted that the lipid emulsion infusion should be continued for at
least 10 minutes after hemodynamic stability is achieved.41 Current
evidence suggests that lipid emulsion works as a carrier to scavenge local
anesthetic away from high blood flow organs that are most sensitive to
local anesthetic toxicity (i.e., the heart and brain) and redistribute it to
organs that store and eliminate the drug (i.e., muscle and liver,
respectively).42 In the presence of persistent cardiovascular collapse
associated with local anesthetic administration, urgent institution of
cardiopulmonary bypass can be lifesaving. The American Society of
Regional Anesthesia and Pain Medicine recently published their most
recent Practice Advisory on Local Anesthetic Systemic Toxicity, and this
includes an up-to-date and comprehensive review of this topic.43

UNINTENDED DESTINATIONS FOLLOWING LOCAL

ANESTHETIC ADMINISTRATION
The direct effects of local anesthetics are critically dependent on where
they are applied. Inadvertent intrathecal injection of local anesthetic can
result in a high thoracic or cervical level of sensory and motor block or
total spinal anesthesia, with transient loss of consciousness and respiratory
arrest. This is most likely to occur during cervical injections or when a
large volume of local anesthetic is used during lumbar injections. Signs

5370
and symptoms of a high spinal progress rapidly and most typically include
flaccid paralysis, apnea, hypotension, bradycardia, and dilated pupils.
They initially include symptoms of sympathectomy, presenting as light-
headedness, dizziness, nausea, and vomiting.35 In addition, the patient may
develop air hunger due to loss of intercostal muscle activity, followed by
phrenic nerve paralysis and eventually apnea due to blockade of the
respiratory center in the brainstem. Blockade of the cardioaccelerator
fibers at T1 to T4 or of the medulla may inhibit sympathetic positive
chronotropic effects resulting in bradycardia, hypotension, or
arrhythmias.44 Blockade of the Edinger-Westphal nucleus with subsequent
loss of efferent parasympathetic activity produces dilated, nonreactive
pupils.45 In the case of subdural injection, symptoms develop more slowly,
typically 15 to 30 minutes after injection, and are commonly asymmetric.
When symptoms do occur, they may progress to respiratory and
cardiovascular collapse as with intrathecal injection. When a high spinal
occurs, ventilation with 100% oxygen with a bag valve mask must be
initiated if phrenic nerve blockade or apnea is present. Endotracheal
intubation may be required to maintain ventilation or protect the lungs
from aspiration. Bradycardia and hypotension should be treated with
crystalloids and atropine, ephedrine, phenylephrine, or epinephrine.44 The
patient may remain awake but paralyzed during a high spinal, so
reassurance that the condition is temporary is warranted as is consideration
of administration of an anxiolytic agent.

VASOVAGAL REACTIONS
Vasovagal reactions, which may include frank syncope, are one of the
most common emergencies encountered in a pain center. Fortunately,
these episodes typically have a benign natural history. Sir William Gowers
first used the term vasovagal in 1907, and vasovagal syncope is now
accepted as the most common form of syncope, accounting for two thirds
of syncopal episodes presenting to the emergency department.46 The
pathogenesis of vasovagal syncope remains uncertain, but the current
understanding is that it results from venous pooling and reduced venous
return and that vigorous contraction of the heart’s chambers when they are
inadequately filled provokes the Bezold-Jarisch reflex, resulting in

5371
paradoxical hypotension and bradycardia. At the onset of a vasovagal
reaction, patients typically appear pale and diaphoretic and complain of
light-headedness, sweatiness, nausea, and tunnel vision. Myoclonic jerks
may accompany vasovagal syncope and may be clinically
indistinguishable from seizure activity. If a patient exhibits signs of a
vasovagal reaction during an interventional pain treatment procedure, the
procedure should be halted, and the patient should be placed supine if not
already in that position. Care should be taken to ensure that the patient will
not fall and sustain a secondary injury. Randomized trials have
demonstrated that leg crossing, and isometric arm exercises can help
prevent progression to vasovagal syncope.47 Most cases of vasovagal
syncope will resolve spontaneously and will require only conservative
measures. In the event that blood pressure and heart rate continue to
decline, an IV line should be placed, crystalloids and oxygen administered,
the patient should be placed on a cardiac monitor and a vasopressor, such
as ephedrine (in 5- to 10-mg increments) or an anticholinergic drug such as
atropine (0.4 to 1 mg) should be administered.35

Complications Associated with Intrathecal Drug

Delivery
When drugs are delivered via the intrathecal route, complications may
arise either due to withdrawal or due to administration of an excessive
dose. In the case of intrathecal baclofen administration, withdrawal may be
particularly severe and can even be fatal. Baclofen is an analogue of the
inhibitory neurotransmitter γ-aminobutyric acid (GABA). It acts as an
agonist of the GABAB receptors in the brainstem, dorsal horn of the spinal
cord, and other CNS regions. Although the mechanism of intrathecal
baclofen withdrawal is not established, it may be due to diffuse
disinhibition of GABAB-modulated pathways.48 Although the most
common manifestation of under dosage of baclofen is pruritus and return
of the patient’s spasticity, abrupt baclofen withdrawal may result in a life-
threatening syndrome characterized by fever, tachycardia, labile blood
pressure or hypotension, malaise, dysphoria, and hallucinations followed
by coma, rebound spasticity more severe than the patient’s baseline,

5372
hyperreflexia or rigidity, paresthesias, priapism in males, and seizures. If
not treated adequately and promptly, the patient may develop
rhabdomyolysis, brain injury, kidney and liver failure, and disseminated
intravascular coagulation.48,49 In some cases, death ensues.50 The
differential diagnosis of intrathecal baclofen withdrawal includes infection,
neuroleptic malignant syndrome, serotonin syndrome, malignant
hyperthermia, and autonomic dysreflexia. Paradoxically, the diagnosis
may be more difficult to make in more severe cases of withdrawal.
Symptoms of intrathecal baclofen withdrawal typically present 1 to 3 days
after interruption of baclofen delivery. Interruption of baclofen delivery
may be due to an exhausted drug reservoir after missing a scheduled refill,
pump malfunction, catheter kinking or disruption, or mistakes in drug
formulation or pump programming. Restoration of adequate intrathecal
baclofen delivery by addressing pump problems or by lumbar puncture or
drain represents the most definitive therapy.51 If the pump catheter remains
intact, intrathecal baclofen may be administered via the side port.
Evaluation of the pump should be performed with the manufacturer’s
interrogation device. If interrogation of the pump does not reveal the
underlying problem, a catheter dye study should be undertaken and the
pump should be refilled with medication at the correct concentration. To
conduct a catheter dye study, radiographic contrast is administered through
the side port of the infusion device to assess the integrity and position of
the intrathecal catheter. Oral and enteral baclofen administration (up to
120 mg per day of baclofen in six to eight divided doses in adults),
accompanied by IV benzodiazepine administration should be undertaken
until intrathecal baclofen delivery is restored. Oral and enteral baclofen
alone are often insufficient to treat withdrawal from intrathecal baclofen.
Continuous or intermittent infusions of diazepam or midazolam may be
rapidly titrated upward until muscle relaxation, cessation of seizure
activity, and normal blood pressure and temperature are restored. Propofol
infusion and chemical paralytic agents may also be used in the intubated
patient.52 The patient should be treated in a setting where critical care
monitoring and ventilator and cardiovascular support is available. In some
cases, patients with hyperthermia have been treated with dantrolene. In
case reports, cyproheptadine has proven helpful.48,53 In contrast, baclofen

5373
overdose typically presents with somnolence, hypothermia, comas,
seizures, respiratory depression, hypotonia, and arrhythmias. Treatment
consists of intubation and artificial ventilation as indicated and
immediately turning off the pump with the manufacturer’s programmer or,
if this is not available, emptying the pump reservoir. In cases where the
overdose is detected within the first few hours, withdrawal of 30 to 40 mL
of CSF via the catheter access port of the pump may reverse the
overdose.54 Physostigmine may reverse drowsiness and respiratory
depression (adult dose 0.5 to 2 mg IV over 5 to 10 minutes, may repeat
every 10 to 30 minutes as required; pediatric dose 0.02 mg/kg IV, less than
0.5 mg per minute, may repeat every 5 to 10 minutes as required up to 2
mg maximum).

OPIOID WITHDRAWAL
Opioid withdrawal can also occur in patients receiving intrathecal drug
delivery or systemic opioids and typically manifests with anxiety,
insomnia, yawning, diaphoresis, lacrimation, rhinorrhea, mydriasis,
myalgias, piloerection, nausea, vomiting, diarrhea, and abdominal
cramping.55,56 In patients for whom ongoing opioid therapy is indicated,
treatment consists of resuming opioid therapy. In some cases, an alternate
route of administration may be necessary, such as IV and/or transdermal
delivery for a patient who is no longer able to take oral medications. In
cases where opioid therapy is not indicated, symptoms of opioid
withdrawal may be mitigated with α2-adrenergic agonists such as clonidine
(0.1 to 0.3 mg orally per dose every 6 to 8 hours increasing to a maximum
of 1.2 mg per day57) or lofexidine (0.4 to 0.8 mg orally per dose increasing
to a maximum of 2.4 mg per day). α2-Adrenergic agonists may cause
hypotension, fatigue, lethargy, and dry mouth. Nausea and vomiting may
be treated with IV fluids and antiemetics such as metoclopramide or
prochlorperazine. Diarrhea and colicky abdominal pain may be treated
with loperamide or hyoscine butylbromide.56 Agitation may be treated
with benzodiazepines, although a careful consideration of risks is
necessary anytime concurrent benzodiazepines and opioids are prescribed.
It should be noted that opioids are not a first-line or routine therapy for
chronic, noncancer pain. The Centers for Disease Control and Prevention

5374
(CDC) Guidelines for Prescribing Opioids for Chronic Pain include
several recommendations for determining when to initiate or continue
chronic opioids for chronic pain. Complications from opioid withdrawal
are often avoidable simply from a proper assessment prior to clinical
prescription. In assessing potential risks, the CDC recommends that
clinicians should review their respective state prescription drug monitoring
program data periodically during opioid therapy for chronic pain, ranging
from every prescription to every 3 months.58

Anaphylactic and Anaphylactoid Reactions

At the turn of the 19th century, Charles Richet and Paul Portier coined the
term anaphylaxis when they observed that several dogs died following
repeat challenges with Physalia extracts during experiments that they
reported while guests on Prince Albert of Monaco’s yacht in the
Mediterranean Sea.59 In an anaphylactic reaction, the inciting allergen
binds to previously formed immunoglobulin E (IgE) on the surface of
previously sensitized mast cells and basophils. These cells release
mediators such as histamine, leukotrienes, prostaglandins, bradykinins,
and thromboxanes that cause markedly reduced vascular tone, increased
mucous membrane secretions, and increased capillary permeability.60
Anaphylactoid reactions produce a similar and often indistinguishable
clinical picture but are not IgE mediated. Anaphylactoid reactions occur
through nonimmune-mediated release of mediators from mast cells and/or
basophils or result from direct complement activation.61 Generalized
hypersensitivity reactions may be divided into grade 1 or mild reactions,
grade 2 or moderate reactions, and grade 3 or severe reactions.62 Grades 2
and 3 correspond with anaphylaxis and are clinically similar to
anaphylactoid reactions. Grade 1 reactions are defined by generalized
erythema, urticaria, periorbital edema, or angioedema. Grade 2 reactions
are characterized by dyspnea, stridor, wheezing, nausea and vomiting,
dizziness or presyncope, chest or throat tightness, or abdominal pain.
Grade 3 reactions are defined by cyanosis or an oxygen saturation less than
or equal to 92%, hypotension, confusion, collapse, loss of consciousness,
or incontinence. Cutaneous manifestations such as erythema, itch, and

5375
urticaria are present in almost all cases, although they may be quite subtle.
Therefore, when the diagnosis is unclear, it is crucial to fully undress the
patient and carefully examine the skin. In one retrospective study of 1,149
cases of generalized hypersensitivity treated in the emergency department,
250 cases were assessed as being due to medications; 145 cases were
believed to be due to antibiotics, with the majority being β-lactam
antibiotics. Nonsteroidal anti-inflammatory drugs were implicated in 32
cases, narcotics in 11 cases, radiologic contrast in 7 cases, angiotensin-
converting enzyme (ACE) inhibitors in 4 cases, vaccines in 4 cases, and
other or unclear medications in 47 cases.62 The median interval between
drug administration and fatal collapse is 5 minutes.63 The differential
diagnosis of anaphylactic and anaphylactoid reactions includes asthma
attack, scombroid poisoning, angioedema either secondary to ACE
inhibitors or hereditary, panic attack, and vasovagal syncope (these last
two conditions do not cause urticaria, angioedema, or bronchospasm).
There are no randomized trials of therapies for these potentially fatal
reactions, so most treatment recommendations are on the basis of
consensus. The patient undergoing an anaphylactic or anaphylactoid
reaction should be administered high flow oxygen. Intramuscular (IM)
epinephrine should be given early to all patients with signs of a systemic
reaction such as hypotension, airway edema, or dyspnea (0.3 to 0.5 mg,
1:1,000, IM repeated every 15 to 20 minutes if there is no clinical
improvement). If the reaction appears to be severe and/or imminently life
threatening, IV epinephrine should be given (0.1 mg, 1:10,000, IV over 5
minutes, followed by an IV infusion of 1 to 4 μg per minute as needed).
Patients receiving epinephrine should be monitored in an emergency
department or intensive care unit. Aggressive fluid resuscitation with
isotonic crystalloids such as normal saline should be undertaken.64 One
liter to 2 L should be rapidly infused. Antihistamines such as
diphenhydramine should be given (25 to 50 mg per dose IV or IM) as well
as H2 blockers (e.g., cimetidine 300 mg IM or IV). Bronchospasm should
be treated with inhaled β-adrenergic agents such as albuterol and/or IV/IM
epinephrine. High-dose IV corticosteroids should be administered early,
although their therapeutic effects are seen 4 to 6 hours after administration.
Other therapies which may be considered in anaphylaxis or anaphylactoid

5376
reactions include vasopressin, which has been beneficial in case reports for
severely hypotensive patients, atropine in the setting of severe bradycardia,
and glucagon for patients who are unresponsive epinephrine, particularly if
they are taking β-blockers.60 Pumphrey,63 who attempted to identify and
analyze every fatal anaphylactic reaction in the United Kingdom since
1992, stresses the importance of keeping patients supine with their legs
elevated.

CATASTROPHIC NEURAL INJURIES AND THE

ADMINISTRATION OF PARTICULATE STEROIDS
In the cervical spine, the carotid and vertebral arteries lie in close
proximity to the stellate ganglion, the cervical facet joints, and the cervical
intervertebral foramina. The anterior spinal artery provides the principal
vascular supply to the spinal cord. The anterior spinal artery arises
rostrally from the vertebral arteries and receives input from six to nine
radicular arteries. It is located at the anterior central sulcus and supplies
the anterior two-thirds of the spinal cord. The posterior spinal arteries
supply the posterior one-third of the spinal cord. They are paired and run
just medial to the dorsal roots. The arteria radicularis magna (more
commonly referred to as the artery of Adamkiewicz) is the largest of the
radicular arteries. It is most commonly located at T10 on the left side but
may occur anywhere from T8 to L2 and occurs on the right in 17% of
subjects.65 In addition, the ascending cervical artery and the deep cervical
artery each furnish spinal branches that enter the intervertebral foramina.
These spinal branches not only supply the vertebral column but also give
rise to radicular arteries that accompany the dorsal and ventral roots of the
spinal nerves (Fig. 112.6). In some individuals, the radicular arteries are
substantial in size and reinforce the anterior spinal artery. Such reinforcing
arteries can occur at any cervical level and those radicular arteries that
supply the spinal cord are termed spinal medullary arteries. If reinforcing
radicular arteries are compromised by a transforaminal injection, infarction
of the cervical spinal cord could ensue. If the vertebral or carotid arteries
are entered, infarction of the brainstem and portions of the brain supplied
by the posterior circulation may ensue, causing stroke, often resulting in
death.

5377
FIGURE 112.6 Axial view of cervical transforaminal injection at the level of C6. The needle has
been inserted along the axis of the foramen and is in final position against the posterior aspect of the
intervertebral foramen. Insertion along this axis places the needle behind the spinal nerve and
behind the vertebral artery, which lies anterior to the foramen. Inset: A spinal artery arises from the
vertebral artery. It supplies the vertebral column. Another spinal artery enters the intervertebral
foramen from the ascending cervical artery or deep cervical artery. It furnishes radicular branches
that accompany the nerve roots and ultimately reach the anterior and posterior spinal arteries of the
spinal cord. (Redrawn from Rathmell JP. Atlas of Image-Guided Intervention in Regional
Anesthesia and Pain Medicine. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2011, with
permission. Figure 6-1.)

The first report of a complication attributed to cervical transforaminal

injection of steroids described a patient who died from a spinal cord
infarction.14 The location of the infarction implied that a radicular artery
that reinforced the anterior spinal artery had been compromised, but no
evidence was offered about the mechanism by which the artery had been
compromised. Images of the placement of the needle were not published.
Reports of spinal cord infarction following cervical66,67 or lumbar68,69
transforaminal injection of steroid have appeared, and this topic has been
reviewed in detail.70 Vertebral artery injection with subsequent stroke
involving the posterior circulation has also been reported.71 A similar case
of massive infarction involving the posterior cerebral circulation following
injection of particulate steroid during attempted intra-articular atlantoaxial
joint injection is shown in Figure 112.7.

5378
FIGURE 112.7 Cerebrovascular accident following intra-arterial injection of particulate steroid
during attempted intra-articular atlantoaxial (C1/C2) joint injection. A: Lateral fluoroscopy imaging
demonstrating needle position adjacent to the C1/C2 facet joint. B: Axial magnetic resonance
imaging (T1 FLAIR sequence) of the brain. Frontal (C) and axial (D) computed tomography
angiography of the vertebral arteries; arrows point to a small filling defect within the left vertebral
artery adjacent to the left C1/C2 facet joint, suggesting the point of needle entry in to the vertebral
artery. The proximity of the vertebral artery to the C1/C2 facet joint is immediately apparent from
the images.

The exact mechanism of spinal cord injury following transforaminal

injections has not been determined. As analyzed using MRI, the pattern of
injury strongly implicates a reinforcing radicular artery. Spasm of the
artery would seem to be an unlikely mechanism because it is inconsistent
with the vasodilatory effect of local anesthetic agents when applied to
arterial walls. Embolism of particulate steroids ranks as the leading
hypothesis, but direct evidence is still lacking. In cases involving the
vertebral artery, a similar uncertainty remains. The injection of contrast
medium cannot be an explanation; in the past, direct puncture of the

5379
vertebral artery has been used for angiography. Steroid embolism remains
the most likely explanation.
The guidelines for the conduct of cervical transforaminal injections70
are designed to guard against these complications. These guidelines
stipulate that the needle must be accurately and correctly placed. Once the
needle has been placed, a test dose of contrast medium should be injected
and its flow carefully monitored during injection. That injection tests two
things. First, under normal circumstances, it should show that the injectate
is correctly flowing around the target nerve and into the lateral epidural
space. Simultaneously, but more critically, it shows if an intravascular
injection has occurred.
Neurologic complications of transforaminal injections are typically
catastrophic. They are clinically obvious on the onset of spinal weakness
and numbness. Spinal cord infarction due to embolization of a radicular
artery is clinically indistinguishable from the anterior spinal artery
syndrome, also known as Beck syndrome. Patients develop abrupt onset of
weakness below the level of the infarction, flaccid paralysis, areflexia, loss
of pain and temperature perception, and atonic urinary bladder. Position
and vibratory sensation will typically be relatively intact. Preserved
proprioception at symptom onset has been associated with better
outcomes.72 In contrast to cerebrovascular infarction, spinal cord
infarction is frequently painful. Patients may experience a radicular or
back pain, and some cases, spinal cord infarction will mimic angina
pectoris.73 Later in the clinical course, the patient may develop spasticity,
hyperreflexia, Babinski responses, and clonus.65 In the setting of possible
acute spinal cord infarction, the differential diagnosis may include spinal
cord compression by a mass lesion such as a spinal epidural or subdural
hematoma or abscess, or a herniated nucleus pulposus. When spinal cord
infarction is suspected, emergent MRI of the spinal cord should be
undertaken to rule out the presence of any space-occupying lesion that
may be amenable to surgical decompression. If spinal cord infarction is
present, sagittal T2-weighted MRI scanning performed at least 4 hours
after symptom onset commonly reveals “pencil-like” hyperintensities and
cord enlargement. Diffusion weighted imaging is particularly sensitive for
detecting ischemic changes in the spinal cord.74 Common diagnostic

5380
pitfalls include failure to image higher levels of the spinal cord when the
patient develops a sensory level that is caudal to the infarction.
One collaboration between the U.S. Food and Drug Administration
(FDA), an expert multidisciplinary working group, and 13 specialty
stakeholder societies reviewed existing evidence and produced a consensus
to enhancing the safety of neuraxial injections.75 A few of these notable
endorsed clinical considerations included the following:
A. Cervical and lumbar interlaminar ESIs should be performed using
image guidance, with appropriate posteroanterior, lateral, or
contralateral oblique views and a test dose of contrast medium.
B. Cervical and lumbar transforaminal ESIs should be performed by
injecting contrast medium under real-time fluoroscopy and/or digital
subtraction imaging, using an anteroposterior view, before injecting
any substance that may be hazardous to the patient.
C. Cervical interlaminar ESIs are recommended to be performed at C7–
T1 but preferably not higher than the C6–C7 level.
D. Particulate steroids should not be used in therapeutic cervical
transforaminal injections.
E. A face mask and sterile gloves must be worn during the procedure.
F. Moderate-to-heavy sedation is not recommended for ESIs, but if
light sedation is used, the patient should remain able to
communicate pain or other adverse sensations or events.
There is no emergency management known to reverse spinal cord
infarction. Many of the principles guiding treatment of acute spinal cord
infarction are derived from experience treating ischemic cerebrovascular
accidents. Initially, emphasis should be placed on reducing the likelihood
of secondary injury to the spinal cord by preventing hypotension and/or
hypoxia. In addition, rapid triage and transport to a definitive care facility
with appropriate imaging, critical care, and surgical capabilities should be
undertaken. In the case of ischemic cerebrovascular accidents, induced
hypertension to achieve a mean arterial pressure of 20% to 30% above
baseline or to achieve a predefined target mean arterial pressure has been
advocated, although this therapy remains controversial.76 Although aspirin
has been advocated for the treatment of spinal cord infarction related to
atherosclerotic disease or dissection, principally on the basis of its use in

5381
the treatment of ischemic stroke, there does not appear to be a role for
antiplatelet or anticoagulant therapy in the treatment of spinal cord
infarction presumed secondary to embolization of particulate steroids. In a
prospective study of 77 patients with acute neurologic deficits secondary
to spinal cord injuries, patients treated with 7 days of volume resuscitation
with crystalloids, transfusion of blood products to maintain a hematocrit
greater than 32, as well as dopamine and norepinephine (Levophed) as
needed to maintain a mean arterial blood pressure greater than 85 mm Hg
had better neurologic outcomes than historical controls.77 This therapy has
not been studied in prospective randomized controlled trials. One 2014
meta-analysis examining over 13,000 patients found that blood pressure
reduction started within 7 days of acute stroke led to an increase in risk of
mortality within 30 days,78 although it had no effect on long-term
mortality. Treatment of nonpenetrating acute spinal cord injury with
methyl prednisolone remains controversial despite evaluation in three
large, prospective randomized double-blind controlled trials.79–81 At the
current time, there is insufficient evidence to advocate routine
administration of methylprednisolone to patients with acute spinal cord
infarction. Standard measures to prevent complications of acute paraplegia
should be implemented, including measures directed at prevention of deep
venous thrombosis and pulmonary embolus, as well as bladder
catheterization if indicated. Early consultation with physiatrists should be
undertaken in order to optimize functional recovery and prevent
development of spasticity and decubiti.

Conclusion
Although emergencies in the pain clinic are quite rare, when they do occur
they can be catastrophic and even deadly. The pain specialist should be
familiar with the most common complications and their mechanisms as
well as techniques that can be used to reduce the risk of said
complications. Familiarity with common complications, including their
clinical presentations and natural histories, will facilitate prompt
recognition and treatment, thereby improving the chances of good
outcomes. Pain specialists should educate patients about specific signs and

5382
symptoms of complications that may ensue from their treatment and
provide them with clear instructions for reaching members of the pain
clinic staff or emergency health care providers in a timely manner, both
during clinic hours and on evenings and weekends, in order to achieve
prompt identification and treatment of complications when they arise.

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C H A P T E R 11 3
Pain Management in the
Emergency Department
JAMES R. MINER

The specialties of both emergency medicine and pain medicine are

relatively new members of the modern house of medicine. The first
academic department of emergency medicine was established in 1971, and
the American Board of Medical Specialties recognized emergency
medicine as a distinct specialty by conferring primary board status only 30
years ago. The numbers of visits to US emergency departments (EDs) have
increased markedly over the past decade. From 2005 to 2015, the annual
ED visit volumes increased from 115.3 million to 136.3 million, a 20%
increase following a similar increase in the previous decade.1 There are
more than 34,000 active board-certified emergency physicians, 31,000 of
whom are represented by the American College of Emergency Physicians
(ACEP).
EDs provide care for patients with an extraordinarily broad range of
illnesses and injuries associated with both acute and chronic pain. Pain is
common in the ED, with up to 42% of ED visits being related to painful
conditions.2 It is commonly believed that injury and trauma are
responsible for the majority of ED visits associated with pain; however,
this impression is misleading. A landmark multicenter study of adults
presenting to EDs in the United States and Canada with moderate to severe
pain found that two-thirds of patients presentation with pain from medical,
rather than traumatic, conditions.3 Major categories of discharge diagnoses
reported in this study appear in Figure 113.1.

5387
FIGURE 113.1 Major categories of discharge diagnoses among patients presenting to the
emergency department (ED) with moderate to severe pain. Note: Other diagnoses present for 243
patients. URI, upper respiratory tract infection; UTI, urinary tract infection. (Data from Todd KH,
Ducharme J, Choiniere M, et al. Pain in the emergency department: results of the Pain and
Emergency Medicine Initiative (PEMI) multicenter study. J Pain 2007;8[6]:460–466.)In the United
States, the ED serves as a safety net for our fragmented health care system. Pain is but one of many
conditions for which emergency physicians not only treat acute clinical presentations but also care
for those with chronic or recurrent painful conditions who are unable to access other parts of the
health care system. Emergency physicians also frequently manage pain in the course of performing
emergent diagnostic and therapeutic procedures.

This chapter discusses the prevalence of acute and chronic pain in the
ED, its assessment, barriers to adequate pain treatment, the influence of
substance use disorders and aberrant drug-related behaviors on ED pain
practices, as well as a variety of commonly employed pain treatment and
procedural sedation modalities. Space limits prohibit a discussion of the
wide variety of specific painful conditions that present to the ED.

The Prevalence of Pain in the Emergency

Department
Pain is the most frequent reason for seeking ED treatment, and as a part of
the presenting complaint, pain accounts for over 70% of visits to US
EDs.3–5 A study conducted by Tanabe and Buschmann,6 found that among
adults treated at one Chicago ED, 78% presented with a chief complaint
related to pain. Of these patients, only 47% received analgesics. For
patients receiving analgesics, an average of 74 minutes elapsed from the

5388
time of arrival to the time of treatment.
Cordell et al.4 reported an analysis of secondary data from an urban,
tertiary-care ED using explicit data abstraction rules to determine the
prevalence of pain and to assign painful conditions into standard
categories. With inclusion of all age groups, they found evidence of pain in
61% of patients. Pain was the chief complaint for 52% of patient visits.
After excluding patients less than 5 years of age for whom chart reviews
are obviously less reliable, almost 70% of patient encounters involved pain
complaints.
Although the high prevalence of pain among ED patients is well
documented, the underlying conditions responsible for pain in this
population are less well characterized. In Cordell et al.’s4 retrospective
study, 11% of patients presenting to the ED were judged to be suffering
from pain that was chronic in nature. In a larger prospective multicenter
study conducted in the United States and Canada, 44% of ultimately
discharged patients presenting to the ED with pain reported underlying
chronic pain syndromes. In one-half of these cases, the ED visit was
prompted by an exacerbation of this chronic pain condition. Importantly,
patients with chronic pain reported three to four times the number of
annual physician visits when compared to those without chronic pain.
Median and mean durations of symptoms for those reporting chronic pain
syndromes were 24 and 52 months, respectively.3 For physicians who
view themselves as experts in the management of acute medical and
surgical emergencies, chronic pain may represent a less familiar condition
with which to contend.
EDs frequently treat patients with chronic or recurrent pain who are
often frustrated by a lack of information about ongoing pain management
and poor access to specialty-level care. In a 2007 study, 500 US adults
with chronic or recurrent pain and an ED visit within the past 2 years were
interviewed.7 Sixty percent were female, their median age was 54 years,
two-thirds were under the care of a physician, and 14% were uninsured.
They reported an average of 4.2 ED visits within the past 2 years.
Relatively large proportions reported pain relief during the ED visit, and
57% endorsed that “the ED staff understood how to treat my pain” as
“definitely true.” Although over three-fourths of patients felt receiving that

5389
additional information on pain management (82%) or referrals to
specialists (74%) was “extremely” or “very” important, only one-half
reported receiving such referrals (46%) or information (55%). A
significant minority (11%) reported that the “ED staff made me feel like I
was just seeking drugs.” The majority (55%) were “very” or “completely”
satisfied with their medical treatment, whereas 24% were “neutral” to
“completely” dissatisfied. In multivariate models, greater age, male
gender, higher level of education, shorter waiting time, use of imaging,
and pain relief contributed to patient satisfaction with ED care.
Findings from this survey provide a more precise estimate of the
prevalence of ED use associated with chronic and recurrent pain in the
United States. The final survey incidence rate of adults reporting a recent
ED visit for chronic or recurrent pain was 15% of all those reached by
phone. Given the US adult population of approximately 225 million, this
survey incidence rate suggests that 34 million adults meet our criteria of an
ED visit within the past 2 years for chronic or recurrent pain. Within this
population, approximately 43%, or 15 million people, experience recurrent
pain, whereas 57%, or 19 million people, have underlying chronic pain
syndromes.
Pain management in the ED has received increased emphasis over the
past two decades, including increased emphasis on patient satisfaction
surveys, and The Joint Commission’s emphasis on analgesia.8 There have
been a large number of important findings showing that analgesia in the
ED is often inadequate, including an Institute of Medicine report,9 leading
to emphasis on improving pain treatment. This emphasis has likely
resulted in improvements in pain treatment in the ED but may have had the
unintended consequence of increasing the use of opioids in the ED and
after ED care.
The high prevalence of acute and chronic pain in the ED, and the
increased emphasis on its treatment, has led to the question of the role of
EDs in the increasing use of opioids in the United States.10,11 Among 20-
to 29-year-olds, emergency medicine ranks third among specialties in
terms of the number of opioid prescriptions, writing 12% of the total
number of prescriptions.12 In one study, 17% of ED patients were
discharged with an opioid medication, the majority of which were small

5390
pill counts and immediate-release formulations.13 A recent study found
that for opioid-naive patients, the odds ratio for developing recurrent use
after a single prescription for opioids versus a nonopioid prescription from
the ED was 1.8.14 This is difficult to interpret because many of the patients
who received an opioid may have had more pain or a more severe injury
than those who did not, but it highlights the need for attention to the risk of
recurrent opioid use when they are used. The risk of opioids from the ED
on patients in the ED with chronic or recurrent pain who already use
opioids is much likely larger but is difficult to quantify. This complicates
pain treatment in the ED and makes it a difficult challenge for emergency
physicians.15
The increase in deaths associated with opioid abuse has heightened
concern16,17 and has led to the development of some actions to decrease
the risk to patients. This includes the U.S. Food and Drug Administration’s
proposal for the establishment of physician education programs for the
prescribing of long-acting and extended-release opioids as part of the
national opioid risk evaluation and mitigation strategy (REMS) program.18
Statewide opioid prescribing guidelines, such as those developed by the
Utah Department of Health19 and the Washington Chapter of the ACEP,20
and guidelines developed by individual physician groups have shown
promise in decreasing opioid prescription overdoses.21 ACEP has also
developed a policy on the use of opioids that clarifies the use of state
prescription monitoring programs, the treatment of back pain with opioids,
and the use of different opioids.22 As research advances and policies
develop, the role of EDs in opioid abuse will be further explored and the
effects mitigated.

The Assessment of Pain in the Emergency

Department
Pain is inherently subjective and inevitably complex. Patients experience
pain and suffering as individuals; clinicians assess it only indirectly. The
emergency provider’s task is to use a commonly understood vocabulary
and classification system in assessing pain so that our findings can be
communicated consistently. Only by quantifying the pain experience in

5391
meaningful ways can we move beyond practices that are influenced by
myth and opinion toward a scientific approach to our many questions
regarding the pain experience. This challenge is at the root of the
difficulties in treating pain and not only in the ED; thus, issues
surrounding pain assessment should have primacy in our attempts to
understand our patients’ pain experiences.
EDs employ a number of practical unidimensional pain assessment
tools. Viewing pain as the “fifth vital sign,” as encouraged by The Joint
Commission on Accreditation of Health Care Organizations, has fostered
the widespread use of such tools. For those without cognitive impairment,
pain intensity is routinely assessed with either an 11-point numerical rating
scale (NRS) or a graphical rating scale (GRS). The NRS is sensitive to the
short-term changes in pain intensity associated with emergency care and is
the most commonly employed pain assessment instrument. GRS or picture
scales are particularly useful for populations with limited literacy,
including children. The visual analog scale (VAS) is used by some EDs;
however, this instrument is more commonly employed in research settings.
There is no demonstrated advantage in using a VAS over an NRS in the
ED setting; both are reliable and valid measures of pain intensity. A
patient’s answer to the query “Do you want more pain medication?”
however, has been shown to be an unreliable measure of pain or relief, and
descriptive pain scales are likely to prove more accurate and reliable.23
Among nonverbal patients, including infants or those with cognitive
impairment and dementia, a number of observational pain scales are
available for use. Both the Face, Legs, Activity, Cry, and Consolability
(FLACC) observational scale for use in very young children24 and the Pain
Assessment in Advanced Dementia scale for use in the setting of advanced
dementia25 are used with some frequency in the ED; however, adequate
observational pain assessments are less the exception than the rule.
No matter the specific pain scale used, assessments should be repeated
after therapeutic interventions and at the time of ED discharge. One
multicenter study found that relatively few ED patients are reassessed after
an initial pain score, reporting that fewer than one-third of ED patients
presenting with moderate to severe pain had repeat pain assessments while
in the ED.3 Despite efforts to promote pain intensity as an outcome

5392
measure with which to judge the quality of ED pain practice, the finding
that pain intensity is measured only once in most EDs may mirrors
medicine’s traditional view of pain as a diagnostic indicator rather than an
outcome deserving of attention in its own right.

Oligoanalgesia in the Emergency Department

Notwithstanding the clinician’s duty to provide compassionate care, pain
that is not acknowledged and managed appropriately causes anxiety,
depression, sleep disturbances, increased oxygen demands with the
potential for end-organ ischemia, and decreased movement with an
increased risk of venous thrombosis.26 Failure to recognize and treat pain
may also result in dissatisfaction with medical care, hostility toward the
physician, unscheduled returns to the ED, delayed complete return to full
function, and, potentially, an increased risk of litigation.27 Although
adequate analgesia in the ED would appear to be an important goal of
treatment, the underuse of analgesics, termed “oligoanalgesia” by Wilson
and Pendleton28 in 1989, occurs in a large proportion of ED patients. A
variety of factors are felt to give rise to pain under treatment, and these are
listed in Table 113.1.

TABLE 113.1 Factors Contributing to Emergency Department

(ED) Oligoanalgesia
Lack of educational emphasis on pain management
Inadequate ED quality improvement systems
Lack of ED pain research, particularly among geriatric and pediatric populations
Emergency providers’ concerns regarding opioid addiction and abuse
Fear of opioid adverse effects
Racial and ethnic bias

Emergency medicine investigators have identified a number of risk

factors for oligoanalgesia, ranging from patient factors to physician
variation.29 As in other settings, the very young or old tend to receive less
intensive treatment for pain in ED. Studies have documented
oligoanalgesia and delays to analgesic administration among those of
minority ethnicity for a variety of painful conditions, even when objective
evidence for the presence of pain is obvious (e.g., long-bone

5393
fractures).2,30–33 Although patients’ expectations for pain treatment and
perceptions of pain intensity don’t differ by ethnic groups, when patients
are matched for socioeconomic factors, differences have been noted in the
manner in which patients of different cultural backgrounds express their
pain. Differences in the interactions of physicians and patients of different
ethnic groups have been described, and subtle differences within these
interactions may affect the physician’s pain assessment.34 When affect,
actual patient–physician interaction, and cultural expressions of ethnicity
are removed from a case presentation, such as through written clinical
vignettes, patients with similar pain tend to be similarly treated by
physicians.35 Cultural discordance between the patient and the physician
may hinder the ability of patients to confer an understanding of their pain
to the physician.
Of course, any treatment of pain is dependent on the physician’s
accurate assessment of the patient’s pain. In fact, the only predictor of
treatment that Bartfield and colleagues36 found for ED patients with back
pain was the physician’s assessment, regardless of the patients’ ethnicity,
age, or insurance status. Disparities in the treatment of pain are more likely
to result from variations in physicians’ assessment of pain intensity than
variations in treatment among patients judged to have similar degrees of
pain.
Although emergency physicians may be reluctant to accept a patient’s
report as the most reliable indicator of pain, and disparities between
patient’s and physician’s pain intensity ratings may lead to inadequately
treated pain, even patients themselves may be reluctant to report the
presence of pain and its intensity. This may be due to low expectations of
obtaining pain relief, fear of analgesic side effects, and perhaps the notion
that pain is to be expected as part of an underlying disease or from medical
treatments. Some patients exhibit an inappropriate fear of addiction when
prescribed opioids or fear the stigma associated with opioid use, even in
the short term.

Pain and Opioid Abuse in the Emergency

Department

5394
ED personnel commonly identify patients who they feel are attempting to
obtain opioids for illegitimate purposes. Although drug addiction occurs in
all patient populations, it is likely that the ED sees a higher proportion of
such patients than a typical office-based practice. Unfortunately, the true
prevalence of addiction and aberrant drug-seeking behaviors in the ED is
unknown and difficult to measure.37 When the prevalence of such
problems is overestimated, oligoanalgesia is the predictable result.

Definitions
In discussing issues of chemical dependency and aberrant behaviors
related to opioid use, a valid system of nomenclature is necessary for clear
communication and measurement. Historically, the meaning of different
terms has changed, particularly in light of the increased use of chronic
opioid therapy for cancer and noncancer chronic pain conditions. In
treating pain in this population of patients with chronic opioids, confusion
over the concepts of physical dependence, tolerance, addiction, and
pseudoaddiction may constitute a barrier to understanding and to
appropriate treatment. These phenomena are discrete, and standard
definitions may be helpful in caring for such patients. Currently accepted
definitions of these include the following: Addiction is a primary, chronic,
neurobiologic disease with genetic, psychosocial, and environmental
factors influencing its development and manifestations. It is characterized
by behaviors that include one or more of the following: impaired control
over drug use, compulsive use, continued use despite harm, and craving.
Physical dependence is a state of adaptation that often includes tolerance
and is manifested by a drug class–specific withdrawal syndrome that can
be produced by abrupt cessation, rapid dose reduction, decreasing blood
level of the drug, and/or administration of an antagonist. Tolerance is a
state of adaptation in which exposure to a drug induces changes that result
in a diminution of one or more of the drug’s effects over time.
Pseudoaddiction is a term which has been used to describe patient
behaviors, including drug-seeking behavior, that may occur when pain is
undertreated. Patients with unrelieved pain may become focused on
obtaining medications, may “clock watch,” and may otherwise seem

5395
inappropriately “drug seeking.” Even such behaviors as illicit drug use and
deception can occur in the patient’s efforts to obtain relief.
Pseudoaddiction can be distinguished from true addiction in that the
behaviors resolve when pain is effectively treated; the use of the term
pseudoaddiction has fallen out of favor, as it is difficult to discern between
the patient who finally achieves adequate pain control and the rare, but
worrisome, patient who initially presents with poorly controlled pain and
subsequently reports improvement but is actually diverting the opioids
prescribed for nonmedical use.
The term substance abuse is particularly problematic and resistant to
precise definition. The American Psychiatric Association has defined
substance abuse as a maladaptive pattern of drug use associated with some
manifest harm to the user or others. Other groups using consensus
methodology have defined abuse as any use considered to be outside of
socially accepted norms. Determining the bounds of “socially accepted
norms” within the broad range of social strata treated within any ED is a
difficult task. Physicians may believe that they “know abuse when they see
it,” and its identification may be influenced by subjective judgments that
may or may not correspond to socially accepted norms for the index
patient’s particular social group.38 Often, the term substance misuse is
applied to behaviors that are not perceived as particularly extreme (e.g.,
taking opioid analgesics to relieve symptoms other than pain such as
anxiety or boredom).
The difficulty in determining whether a given set of behaviors fall
within accepted definitions of substance use, misuse, or abuse has
important implications outside the clinical realm. Physicians may prescribe
controlled substances for the treatment of pain, whereas patients may use
these drugs to treat a broad range of symptoms with varying degrees of
relatedness to underlying pain syndromes and may, in fact, use drugs in a
manner totally unrelated to the physicians’ intent (i.e., to obtain euphoric,
rather than analgesic, effects). Given the unclear distinctions between use,
misuse, and abuse and a regulatory climate in which practitioners
prescribing patterns are increasingly scrutinized, emergency physicians are
required to be cautious when the need to prescribe opioids to patients with
whom they expect to have only a transitory relationship.

5396
 Using any definition, substance abuse is a highly prevalent problem in
the ED.11,39 The National Survey on Drug Use and Health reports that in
2015, an estimated 10.1%, of the population aged 12 years or older used an
illicit drug during the month prior to the survey interview.40 Importantly,
the survey documents a 13.6% reported lifetime nonmedical use of pain
relievers in 2014. To be considered nonmedical use, the respondent had to
take drugs not prescribed for them or take them only for the “experience or
feeling” they caused. Specific analgesics included Vicodin, Lortab, or
Lorcet (combination analgesics containing hydrocodone); Percocet,
Percodan, or Tylox (combination analgesics containing oxycodone);
hydrocodone; OxyContin (extended-release oxycodone); methadone; and
tramadol.
In contrast to the prominence of ED-based data collection systems in
efforts to monitor deleterious outcomes associated with substance abuse,
relatively few studies have systematically assessed substance abuse
prevalence and treatment needs in the ED population.41 As an example, the
Drug Abuse Warning Network is a federally financed, public health
surveillance system that monitors drug-related ED visits and drug-related
deaths investigated by medical examiners and coroners. This reporting
system involves hundreds of hospital EDs throughout the United States
and provides valuable data with which to monitor drug abuse trends. In
contrast to this large monitoring research enterprise, relatively little focus
has been given to use of the ED as a setting in which to intervene in
substance abuse problems.
In a study of trauma patients, Soderstrom et al.42 assessed the
prevalence of psychoactive substance use disorders in a large, unselected
group of seriously injured patients treated in one Baltimore ED, using
standardized diagnostic interviews and explicit criteria. Psychoactive
substance use disorders were diagnosed using the Structured Clinical
Interview, an instrument based on the Diagnostic and Statistical Manual of
Mental Disorders. Of 1,118 patients consenting to the study, 71.8% used
alcohol, 45.3% used illegal drugs, 18.8% demonstrated active drug abuse
or dependence, and 32.1% demonstrated concurrent alcohol abuse or
dependence.43 The high rate of substance use and abuse among trauma
patients, and the fact that trauma usually is associated with pain that

5397
requires treatment, complicates the treatment of pain from trauma.

Pain and “Drug-Seeking Behavior” in the Emergency

Department
The preceding discussion makes clear the high prevalence of both pain and
substance use disorders in the ED. Although acute and chronic pains are
far more common than substance use disorders, it is inevitable that
emergency physicians will frequently encounter patients presenting with
both pain and substance use disorders. Professional discussions of pain
treatment in the ED frequently center on concerns of being duped by such
patients who fabricate painful symptoms in order to obtain opioids, so-
called “drug-seeking behavior.”34,37 Drug-seeking behaviors may
represent an entirely appropriate response by those with chronic pain who
are routinely undertreated by the medical profession and for who
comprehensive pain treatment centers are in short supply. Although the
term drug-seeking behavior is poorly defined, it is used in the emergency
medicine literature and will be used with acknowledgment of its
imprecision.
Only a limited amount of emergency medicine research has addressed
this problematic issue. In 1996, Zechnich and Hedges44 attempted to
measure community-wide use of ED services by patients at high risk for
drug-seeking behavior. In this retrospective, observational study, patients
were categorized as exhibiting drug-seeking behavior if they sought care at
a university hospital in Portland, Oregon, for a specific pain-related
diagnosis (i.e., ureteral colic, toothache, back pain, abdominal pain, or
headache) and were either independently identified on at least one other
local hospital’s “patient alert” list or suffered a drug-related death during
the year in question. After identifying 33 such patients, they determined
the frequency of their ED visits at each of seven local hospitals and
conducted detailed chart reviews of their visits at three of these hospitals.
The patients identified as drug seeking were generally young, and one-half
of drug seekers were female. This suggests that drug-seeking behaviors are
exhibited (or identified) more commonly among female ED patients with
substance abuse problems than among males.39,45 The 33 patients visited

5398
EDs, urgent care clinics, or were hospitalized a total of 379 times over the
study period, for an average of 12.6 visits per person annually.
Interestingly, although chart reviews identified 17 patients who were told
that he or she “would receive no further narcotics” at a given facility, these
patients subsequently received controlled substances from another hospital
in 93% of cases and from even the same facility in 71%. The authors
suggested that information sharing between hospitals could help to identify
drug-seeking patients and promote more consistent community-wide care
and appropriate substance abuse interventions.
The need for information sharing has led to the development of
statewide prescription monitoring programs.46 These programs allow
physicians to determine whether a patient has received opioid medications
regardless of their individual report, allowing easier identification of
patients who are misrepresenting their current opioid use. Such monitoring
systems are generally not required and are not universal, but data indicate
they are successful, at least more so than the previous attempts at internal
lists many EDs had used, and their use should be expanded.47 It has been
shown that the use of such lists alters physicians’ prescribing behavior,
both by increasing pain medications for patients who do not exhibit
frequent use and identifying patients at risk for opioid abuse or
dependence related to their treatment.48,49 Although early versions of these
monitoring programs were difficult to access and use, they are becoming
increasing usable and are becoming a typically step in the prescribing of
opioids in the ED.50 Prescription drug monitoring programs are generally
underused in EDs, and nationwide enrollment is low among emergency
physicians. In order to improve this, an expert panel was convened by
ACEP and made policy recommendations within these main themes:
Enrollment should be mandatory, with an automatic process to mitigate the
workload; registration should be open to all prescribers; delegates should
have access to prescription drug monitoring program to alleviate workflow
burdens; prescription drug monitoring program data should be pushed into
hospital electronic health records; prescription drug monitoring program
review should be mandatory for patients receiving opioid prescriptions and
based on objective criteria; the prescription drug monitoring program
content should be standardized and updated in a timely manner; and states

5399
should encourage interstate data sharing.51
It has been difficult to quantify the overall effect of such systems,13 and
they run the risk of resulting in unfair treatment of the patient if the
information is not used properly and it is a context appropriate to the
patient.52 It is likely, however, that improved information will reduce risks
to patients and improve care, both in terms of identifying patients who
have developed substance abuse problems related to their pain treatment
and in terms of avoiding misidentifying patients exhibiting behaviors that
appear associated with addiction but are in fact exhibiting pseudoaddiction
related to oligoanalgesia.

Pain and Substance Abuse in the Emergency

Department: A Balanced Perspective
In managing pain, emergency physicians are responsible for beneficence
as well as nonmaleficence. We must treat pain and ameliorate suffering
while minimizing the extent to which our treatment strategies enable
substance abuse by our patients. For the vast majority of patients
presenting with a first episode of acute pain, whether from trauma, acute
medical illness, or procedures performed in the ED, there is little danger of
enabling substance abuse and a great deal of room for improvement in the
quality of analgesic practices. For a small subset of ED patients,
particularly for those presenting with chronic or recurrent pain syndromes,
the physician may have legitimate concerns regarding underlying
substance abuse or related disorder. Our task is to balance the often
unclear risk of fostering substance abuse, and even diversion, in this subset
of patients with the well-known and well-documented risk of under
treating painful conditions.
Certainly, the presence of an obvious painful condition (e.g.,
appendicitis, fracture) should preempt concerns about illegitimate drug-
seeking behaviors. Given the high prevalence of chronic pain and the
widespread unavailability of chronic pain management resources,
particularly for populations served by the ED, pseudoaddiction is the most
likely cause for a large proportion of drug-related behaviors deemed
aberrant. In particular, patient reports of distress associated with

5400
unrelieved symptoms, aggressive complaining about the need for higher
doses of analgesics, and unilateral dose escalation by the patient are
suggestive of pseudoaddiction. Establishing the diagnosis of
pseudoaddiction is particularly difficult if the patient has both pain and a
comorbid substance use disorder; however, the two can coexist. The
signature of pseudoaddiction is that aberrant behaviors disappear when
adequate analgesics are given to control pain.
In dealing with complex chronic pain patients, the emergency physician
practicing in isolation may exhibit symptoms of despair and direct his or
her anger toward the patient with pain, resulting in more alienation of
patients who may have already been abandoned by other sectors of the
health care system. This is particularly likely to happen in communities
without multidisciplinary treatment centers for either substance abuse
disorders or chronic pain and for those with inadequate health care
insurance. Thus, the patient with chronic pain joins the larger group of
those with unmet health care needs that currently crowd our EDs. The
hectic nature of emergency medicine practice often does not allow
sufficient time for precisely characterizing patients with complex pain
complaints, and clinicians may lump legitimate pain behaviors with the
ploys of those seeking opioids inappropriately. Both groups of patients
may be ultimately mistrusted and treated with disdain.
Aside from considerations of pseudoaddiction, chronic pain is often
accompanied by mood disorders and psychiatric comorbidities that
complicate the management of these challenging patients.26 The presence
of aberrant drug-related behaviors in patients with borderline personality
disorders may represent an expression of fear and anger or an attempt to
cope with chronic boredom. Patients may use opioids and alcohol in
attempts to lessen symptoms of anxiety, panic disorder, depression, or
insomnia. Emergency physicians often receive limited training in dealing
with such disorders and the specialty’s deficiencies in dealing with such
problems have been documented.53 Psychiatric consultation, if available,
may be useful in both suggesting alternative causes for aberrant behaviors
and tailoring the physician’s therapeutic approach to deal with these
complicating factors.
For some patients, aberrant drug-related behaviors represent criminal

5401
intent to divert or sell controlled substances. The prevalence of behaviors
occasioned by such intent is unknown, and it is likely that in many cases,
multiple etiologies of aberrant behaviors coexist.37,54 Certainly, patients
with active or past substance use disorders are at increased risk for injuries
and illnesses that can lead to chronic pain (e.g., motor vehicle injury).
Finally, although federal regulators and state medical boards do not
perceive emergency medicine as a specialty prone to inappropriate
prescribing, and investigations of emergency physicians are rare, if not
unheard of, many emergency physicians express fears of such scrutiny or
sanctions related to prescribing or administering opioids. Although this
concern is often voiced, it seems likely that this fear represents concern
about other, less obvious physician uncertainties related to pain
management and substance abuse disorders. Emergency physicians may be
concerned about being overburdened by the inherent difficulties of
managing patients with complicated pain syndromes and the potential of
coexisting substance abuse disorders.

The Example of Sickle Cell Disease

The condition that best exemplifies the problem of ED-based
pseudoaddiction is sickle cell disease. Vaso-occlusive pain crises are the
most common reason for ED visits by patients with sickle cell disease, and
the genetics, molecular biology, and pathophysiology of this disease are
relatively well understood. Although the management of sickle cell vaso-
occlusive pain crises is viewed as challenging by emergency physicians, it
has been a relatively neglected area of research investigation by the
specialty.55
Despite our understanding of the sickle cell disease process, many
health professionals are reluctant to prescribe adequate doses of opioids for
these patients experiencing pain largely due to addiction concerns, and that
care is frequently insufficient and delayed.56 In one survey study, 53% of
emergency physicians were of the belief that more than 20% of patients
with sickle cell disease were addicted to opioids, whereas only 23% of
hematologists shared this belief. Also, in this survey, 35% of
hematologists reported that they followed pain management protocols

5402
when treating painful crises as compared to only 17% of emergency
physicians.57,58
Nurses’ attitudes regarding the prevalence of addiction among this
patient population are even more extreme, with 63 respondents reporting
that addiction was prevalent.59 Thirty percent of nurses in this survey
reported that they were hesitant to administer high-dose opioids for painful
vaso-occlusive crises. A hesitant approach to ED opioid administration in
the setting of vaso-occlusive pain crises will predictably lead to continued
pain, increased anticipation of pain, and increased patient anxiety. This
experience may generate pain-avoidance manifestations by patients that
are interpreted by physicians as aberrant drug-related behaviors.
Eventually, larger doses of opioids may be administered to control pain
that is spiraling out of control with resultant excessive sedation. This
apparent sedation in the setting of a painful condition may reinforce the
physician’s disbelief in the reality of his or her patient’s initial pain
reports.
It has been demonstrated that this cycle of inadequate care can be
broken by the institution of pain management protocols that emphasize
continuous opioid infusions and sustained courses of orally administered
controlled-release opioids. Tanabe et al. demonstrated in several studies
that the addition of nurse-initiated protocols, including the use of high-
dose opioids, and provider education led to improvements in pain
management.55,56,60,61

Pain Treatment and Procedural Sedation in the

Emergency Department
Effective pain management involves both pharmacologic and
nonpharmacologic modalities. Simply asking about pain and validating the
pain reports impacts patients’ satisfaction with ED pain management. In
one study, patient satisfaction with pain management was predicted more
strongly by the perception that ED staff asked about pain than by the
actual administration of an analgesic.62 Other nonpharmacologic
modalities, such as reassuring the patient that pain will be addressed;
immobilizing and elevating injured extremities; and providing quiet,

5403
darkened rooms for patients with migraine headaches, are important
aspects of quality pain management. Pharmacologic therapies should begin
as soon as is practical after presentation to the ED. Analgesic protocols
allowing early pain treatment can decrease the time to effective treatment
and improve patient outcomes.63,64
Analgesics may be administered by a variety of routes; however, the
vast majority of medications are administered by the oral or parenteral
routes. Oral therapies are most commonly employed as they are
convenient and inexpensive for patients who can tolerate oral intake.64
When pain is severe, analgesics must be given immediately and titrated to
effect, generally by parenteral routes. The intravenous, rather than
intramuscular, route is indicated in this context. Intramuscular injections
are painful, do not allow for rapid titration, exhibit unpredictable
absorption, and result in a slower onset of drug action. Unless intravenous
access is elusive, there is little to recommend the intramuscular route. In
general, it is inappropriate to delay analgesic use until a diagnosis has been
made. In the case of acute abdominal pain, for which surgical dogma
historically discouraged adequate analgesia, studies report no deleterious
effect of intravenous opioid therapy on our ability to make appropriate
diagnoses.65

Specific Treatment Modalities

Analgesics are the most commonly administered class of drug in the ED.
The National Center for Health Statistics reports that analgesics account
for the top three therapeutic classes of drugs used in the ED (Fig. 113.2).40
The majority of analgesics administered were opioids (59%); morphine
being the most commonly used analgesic (20%), followed by ibuprofen
(17%) (Table 113.2).

5404
FIGURE 113.2 Top 10 therapeutic drug classes mentioned at emergency department visits. (Data
from National Center for Health Statistics. National Hospital Ambulatory Medical Care Survey:
2013 Emergency Department Summary Tables. Atlanta, GA: U.S. Department of Health and
Human Services, Centers for Disease Control and Prevention; 2013. Available at:
https://www.cdc.gov/nchs/fastats/emergency-department.htm. Accessed September 1, 2017.)

TABLE 113.2 Analgesics Administered in the Emergency

Department3
Analgesic N (%)
Morphine 148 (20.1)
Ibuprofen 127 (17.3)
Hydrocodone; acetaminophen 93 (12.7)
Oxycodone; acetaminophen 83 (11.3)
Ketorolac 60 (8.2)
Acetaminophen 53 (7.2)
Hydromorphone 36 (4.9)
Antacid 26 (3.5)
Meperidine 24 (3.3)
Fentanyl 23 (3.1)
Metoclopramide 13 (1.8)
Codeine; acetaminophen 12 (1.6)
Oxycodone 10 (1.4)
Naproxen 9 (1.2)
Other 18 (2.4)
Total 735 (100)

NONOPIOIDS
Commonly used ED analgesics include opioids, acetaminophen, and
nonsteroidal anti-inflammatory drugs (NSAIDs). When opioids are
required for pain treatment, nonopioids should be included in order to

5405
potentiate the opioid analgesic effect and decrease the severity of side
effects. Unfortunately, nonopioid agents exhibit an analgesic ceiling effect
and cannot be titrated to effect. This limits their usefulness in the setting of
severe or fluctuating pain; however, they should be used as an adjunct to
opioid therapies unless otherwise contraindicated.
Acetaminophen is indicated for mild to moderate pain and is often
combined with opioid agents. Acetaminophen, unlike NSAIDs, has no
antiplatelet activity or anti-inflammatory effect. Although a great deal of
attention has been paid to acetaminophen hepatotoxicity, especially in the
setting of chronic malnutrition, alcoholism, or liver disease, such effects
are uncommon, particularly when contrasted to the underappreciated high
prevalence of NSAID-related adverse effects
NSAIDs, including salicylates, act to inhibit prostaglandin synthesis by
interfering with cyclooxygenase enzymes. They frequently cause gastritis
and gastrointestinal (GI) bleeding, cause platelet dysfunction, and can
precipitate renal failure in patients with renal insufficiency or volume
depletion, a particular concern in the elderly or those presenting to the ED
with hemodynamic instability. They have a ceiling effect at relatively low
doses.66 Ketorolac, the only parenteral available in the United States, is
commonly used in the ED and is felt to be particularly useful in the setting
of renal colic. One study of renal colic in the ED found that a combination
or ketorolac and morphine resulted in superior analgesia and reduced
adverse effects when compared to the use of either agent alone.67 A recent
study by Motov et al.66 demonstrated that at dose of 10 mg intravenously
has similar analgesic efficacy as 15 or 30 mg, indicating that is likely the
safest dose for emergent therapy.

OPIOIDS
Opioid combination analgesics are commonly used for moderate to severe
pain. Although the opioid component in these agents does not exhibit
ceiling analgesic effects, the nonopioid component dose must be limited;
thus, one cannot titrate these analgesics. The convenience of combination
therapy must be balanced against this limitation. Hydrocodone and
oxycodone combination agents are associated with less nausea and
vomiting and are preferable to codeine combinations agents. Also,

5406
significant proportions of the population are poor metabolizers of codeine,
which must be metabolized to morphine in order to manifest analgesic
effects, further limiting its effectiveness.
The tramadol/acetaminophen combination agent is indicated for acute
pain; however, experience with this agent in the ED setting is limited. In
one recent trial of acute ankle sprains presenting to the ED, the
tramadol/acetaminophen combination agent had comparable clinical utility
to that of hydrocodone with acetaminophen.68 Tramadol’s mechanism of
action is unclear: It binds only weakly to opioid receptors and inhibits the
reuptake of both norepinephrine and serotonin.
Opioids are the mainstay of ED therapy for moderate to severe pain, and
morphine is the standard of comparison for all agents of this class. If
contraindicated due to allergy or other sensitivity, hydromorphone or
fentanyl may be substituted. These opioids can be rapidly titrated
intravenously to control severe pain, allowing early institution of an oral
regimen. Fentanyl has the advantage of being relatively short acting and is
preferred in the setting of multiple trauma, head injury, and potential
hemodynamic instability. Intravenous morphine is the standard of
treatment for severe pain in the ED. Morphine 0.1 mg/kg bolus has been
found to be safe but not usually adequate to effect pain relief.69 Repeat
boluses of 0.05 mg/kg every 5 minutes until pain relief represents a safe
incremental strategy. In patients with impaired hepatic function in the
elderly, hydromorphone may be superior to morphine because it has less
active metabolites. Oral oxycodone has shown to be comparable to
intravenous morphine and when compared to the time of ordering has a
similar time to analgesia to intravenous morphine due to the time needed
to place the intravenous line.64 It is more difficult to titrate, however,
requiring 20 to 30 minutes between doses to observe the full effect rather
than 10 to 15 minutes needed for morphine. A common strategy in a
patient in severe pain is to start oral oxycodone before the intravenous line
is placed and then switch to an intravenous opioid titrated to pain relief.
Agonist-antagonist opioids, such as nalbuphine and butorphanol, have
mixed effects on opioid receptor subtypes, exhibiting ceiling effects on
both analgesia and respiratory depression. Because clinically important
respiratory depression is distinctly rare in the setting of acute pain

5407
treatment, it is difficult to justify their routine use. One possible exception
is for patients with advanced pulmonary disease. A particular drawback is
that one cannot titrate these drugs to maximal effect because of analgesic
ceiling effects. Additionally, these drugs are contraindicated and will
induce withdrawal symptoms in patients who are physically dependent on
opioids, either because of opioid therapy for chronic pain, methadone
maintenance therapy, or active opioid addiction.

PATIENT-CONTROLLED ANALGESIA
The use of patient-controlled analgesia (PCA) has been described in
emergency medicine for both adults and children.70 Although no specific
advantage has been found over the titration of opioids, PCA is at least as
effective in relieving pain. In the setting of high demands on nursing
resources, PCA could serve to ensure that patients’ pain treatment needs
are addressed in a timely fashion. In addition, patients admitted from the
ED to inpatient hospital beds often experience a “pain window” between
the last dose of an analgesic in the ED and the first dose administered on
the hospital ward. Wider use of ED PCA might obviate this common
problem.

ALTERNATIVE DELIVERY ROUTES

Multiple alternative delivery routes for the administration of pain
medications have been described. The use of nebulized fentanyl has been
described and holds promise as a route of opioid delivery that can be
initiated before an intravenous line has been placed.71,72 In addition,
intranasal ketamine73,74 and intranasal ketorolac have been described and
have shown promise.75 Nebulized pain medications, especially for children
who have severe pain but have not had an intravenous line placed, could
be of use in the ED.

PROCEDURAL SEDATION AND ANALGESIA

Patients often present to the ED in need of painful or complex procedures
that require patient cooperation and must be done emergently. Procedural
sedation and analgesia (PSA) practices and policies have evolved rapidly
in the ED, and this is a growing area in the practice of emergency

5408
medicine.76 PSA in the ED is complicated by the occurrence of
unpredictable concurrent events as well as time and space constraints of
the ED. Furthermore, unlike most patients who undergo sedation in other
settings, patients in the ED typically have an unpredictable “nothing by
mouth” (NPO) status, often have concurrent severe systemic disease, and
usually are in severe pain before the procedure begins.77
The indications for ED PSA range from pain control for short painful
procedures to the need for patient compliance with a complex emergency
procedure. The typical target sedation level for ED PSA ranges from
minimal through moderate and deep sedation, depending on the demands
of specific procedures.78 Deep sedation can inadvertently result in the
patient achieving a level of sedation consistent with general anesthesia, but
this is not an intended target level of ED PSA.79
Minimal sedation describes a drug-induced state during which patients
are sedated but are still able to respond appropriately to verbal commands
(according to their developmental age) and whose eyes remain open.
Depending on the agent, it is possible to achieve amnesia of the procedure
at this level of sedation, but by definition, patients will still respond to
their surroundings. It is generally performed for procedures that require
patient compliance but are not typically intensely painful when performed
with local anesthesia. Minimal sedation is typically used for procedures
such as lumbar puncture, evidentiary exams, simple fracture reductions (in
combination with local anesthesia), and the incision and drainage of small
abscesses.
During minimal sedation, cardiovascular and ventilatory functions are
generally maintained, although patients should be monitored for
inadvertent oversedation to deeper levels using oxygen saturation monitors
and direct observation. Agents typically used for minimal sedation include
alfentanil, fentanyl, midazolam, combinations of the two, and low-dose
ketamine.
Moderate sedation is performed on patients who would benefit from a
deeper level of sedation to augment the procedure. Moderate sedation
describes patients sedated to the point at which their eyes are closed but
they open in response to verbal commands (appropriately to their
developmental age) alone or to light tactile stimulation. Patients at this

5409
level usually have an intact airway and maintain ventilatory function
without support. As with minimal sedation, inadvertent over sedation to
deeper levels can occur with moderate sedation.80,81 Appropriate
monitoring including oxygen saturation, cardiac monitoring, and blood
pressure measurements should be done throughout the sedation, and direct
observation of the patient’s airway should be maintained throughout the
procedure. Agents used for moderate sedation in the ED include propofol,
etomidate, ketamine, and the combination of fentanyl and midazolam.
Deep sedation is performed on patients who would benefit from a
deeper level of sedation, often in order to complete a procedure already
begun that requires more patient relaxation than was achieved at a lighter
level of sedation. Generally, amnesia of the procedure is similar between
moderate and deep sedation, and it is not necessary to sedate patients to a
deep level only to obtain amnesia.82 Deep sedation is achieved in the ED
with the same agents as moderate sedation; the difference is in the
intended level of sedation. Monitoring requirements for deep sedation are
similar to those for moderate sedation.
End-tidal carbon dioxide monitoring has also been described in ED
PSA,83,84 and it is generally regarded as the monitor most comparable to
direct observation of the patients airway for detecting changes in the
patients ventilator patterns,85 especially in patients receiving high-flow
oxygen to prevent hypoxia.85 Deeply sedated patients can develop
respiratory depression but generally maintain a patent airway and adequate
ventilation.80,86,87 Patients sedated to this level can progress to a level of
sedation consistent with general anesthesia. This can occur after the
procedure for which the patient was sedated has been completed. Pain is a
powerful stimulant, and after it is removed due to the completion of a
procedure or the application of local anesthesia, patients may progress to a
deeper level of sedation. There is some evidence that the inadvertent
progression to general anesthesia occurs more frequently in patients
targeted for deep sedation than in those undergoing moderate sedation.82
For this reason, and the fact that the occurrence of procedural recall is
similar between moderate and deep sedation, it is usually safer to use
moderate sedation than deep sedation in the ED unless the procedure
requires progressively deeper levels of sedation to complete successfully,

5410
such as the reduction of hip dislocations.
Patients who progress to an unintended level of sedation consistent with
general anesthesia are not arousable, even to pain. The ability to
independently maintain ventilatory function is usually impaired, and
patients often require assistance in maintaining a patent airway. Patients
can quickly progress to the level of general anesthesia using agents
commonly employed for moderate and deep sedation, and physicians
performing ED PSA must be prepared to provide ventilatory support until
the patient’s level of consciousness has improved and they are able to
protect their airway and ventilate normally.
In order to decrease the likelihood of aspiration, patients who are
undergoing moderate or deep sedation in the ED are often kept NPO.
Regardless of the target depth of sedation or the agent administered, there
is insufficient evidence to support specific fasting requirements prior to
procedural sedation. A guideline for emergency physicians has made
recommendations for the proper risk stratification of patients based of their
last oral intake.77 In general, the risk of aspiration from recent oral intake
increases with the depth of sedation and must be balanced with the
urgency of the procedure when deciding whether or not to delay sedation
due to recent oral intake.
Patients who have not had oral intake other than clear liquids for 3 hours
prior to their procedure have a low risk of aspiration at any level of
sedation. In patients with recent oral intake in need of an emergent
procedure, the risk of aspiration is unlikely to outweigh the risk of
delaying the procedure. Because the risk of aspiration likely increases with
the depth of sedation, it is prudent to target the lightest level of sedation
feasible for the necessary procedure. For nonurgent procedures where a
time delay is unlikely to have a negative effect on the patient, patients who
have eaten more than clear liquids in the prior 3 hours should have the
procedure delayed until 3 hours after their last intake. For urgent
procedures falling in between emergency and nonurgent procedures,
lighter levels and shorter durations of PSA should be used as the size of
oral intake taken within 3 hours of the procedure increases.
Patients who are intoxicated, especially with alcohol, can be especially
difficult to sedate. They often have food in their stomachs, and the

5411
achieved level of sedation can be difficult to predict. In emergent
reductions, this increases their risk but does not change the procedure. In
patients who can safely have the procedure delayed, intoxicated patients
may benefit from a delay in their sedation until the progression of their
mental status (getting worse or getting better) can be ascertained through
observation.
ED PSA is necessarily used for patients who are medically healthy or
have uncomplicated coexisting medical conditions (American Society of
Anesthesiologists Physical Classes 1 and 2) and those who have more
significant or life-threatening coexisting medical conditions (Classes 3 and
4). PSA for critically ill children has been described using ketamine88 and
in adults using propofol or etomidate.89 The degree of respiratory
depression noted in these patients was similar to patients with physical
status scores of 1 or 2, but an increased rate of hypotension was seen in
physical status 3 and 4 patients who received propofol. It may be that
ketamine and etomidate are better suited for the emergent sedation of
critically ill patients, but there is not yet sufficient data to make a definite
recommendation.
The ventilatory status of sedated patients must be monitored. This is
generally accomplished with pulse oximetry, capnography, and direct
observation of the patient’s respiratory effort. Pulse oximetry is a sensitive
measure of oxygenation. If a patient receives supplemental oxygen prior to
starting PSA and during the procedure, this monitor may not be as
sensitive to changes in the patient’s ventilatory status. End-tidal carbon
dioxide has been recommended as an additional modality for the
monitoring ventilatory status.84–86,90 It provides a graphic display of
ventilatory status that can be used to detect respiratory depression before it
becomes clinically apparent. In the event of hypoventilation, the end-tidal
carbon dioxide value increases as the respiratory rate decreases. In the
event of increasing airway obstruction, the baseline end-tidal carbon
dioxide value decreases along with a blunting of the waveform due to
increased mixing of the nasal expiratory sample with ambient air due to
the turbulence from the obstruction.
Ketamine use has been described in adults and children undergoing ED
PSA.91,92 Ketamine is a dissociative anesthetic that provides 15 to 20

5412
minutes of sedation when given intramuscularly, with a return to baseline
mental status in 30 to 60 minutes. It can be given in doses of 1 to 4 mg/kg
intramuscularly and should be combined with atropine 0.01 mg/kg to
prevent hypersalivation. The 1 mg/kg dose achieves minimal sedation
sufficient for such procedures as lumbar puncture, dressing changes, and
simple laceration repair. Doses from 2 to 4 mg/kg result in increasingly
deeper levels of moderate to deep sedation. Patients sedated with ketamine
usually maintain a patent airway and ventilate normally. Patients receiving
ketamine should be monitored for respiratory depression and rare
occurrences of laryngospasm.93 Emergence phenomena, unpleasant
perceptual experiences as patients regain consciousness, have been
described in both adults and children.94 The addition of 0.1 mg/kg of
midazolam to ketamine has been described to prevent emergence
phenomena, but no difference in the occurrence of emergency phenomena
has been found with its use.95 Intravenous ketamine is also used for ED
PSA at doses of 1 mg/kg with an onset of 1 to 2 minutes, followed by
moderate sedation lasting 8 to 12 minutes. The adverse effects of
intravenous ketamine are similar to those of intramuscular use.
The combination of fentanyl and midazolam has been used for minimal,
moderate, and deep sedation in the ED.96–99 This combination results in
longer periods of sedation than other agents and carries a higher rate of
respiratory depression than other commonly used agents. Although
adequate for minimal sedation, the high level of respiratory depression and
long duration of action makes this combination less useful for moderate or
deep sedation. Dosing for minimal sedation has been described as 0.1
mg/kg intravenous midazolam followed by 0.05 mg/kg intravenous
fentanyl, with repeated fentanyl boluses every 1 to 3 minutes until the
patient is adequately sedated. The sedation typically lasts 30 to 60 minutes
with a return to baseline mental status by 45 to 120 minutes. This method
of PSA requires direct ventilatory monitoring.
Pentobarbital is a sedative agent typically used for minimal to moderate
sedation for radiologic procedures.100 This agent has no analgesic
properties and patients who appear sedated after its administration can be
aroused with less stimuli than is typical for many of the other agents used
in ED PSA, which is an excellent characteristic for preventing over

5413
sedation for radiologic procedures, but is of limited utility for painful
procedures. The medicine is administered at 2.5 mg/kg intravenously,
followed by 1.25 mg/kg every 5 minutes until adequate sedation is
achieved. Pulse oximetry should be used; however, the rate of respiratory
depression is lower than for other agents.
Methohexital has been used for moderate and deep PSA.101 It is a very
short-acting agent with excellent amnestic properties. It is administered at
1 mg/kg intravenously with 0.5 mg/kg repeat boluses every 1 to 2 minutes
as needed. It has an onset of 30 seconds, with sedation lasting 2 to 4
minutes and returning to baseline within 5 to 10 minutes. It has been
associated with respiratory depression and a quick progression to deeper
levels of sedation than intended and can cause over sedation even when
carefully titrated. It should therefore be used with close ventilatory
monitoring. Compared to propofol, methohexital is similarly effective and
safe with single bolus use but is less safe than propofol when multiple
doses are required. It should be used principally for very brief procedures
expected to last less than 2 to 4 minutes, such as the reduction of simple
fractures and dislocations.
Propofol is well described for ED PSA.79 It is administered as a 1 mg/kg
bolus with repeat boluses of 0.5 mg/kg every 2 to 3 minutes until the
patient achieves the desired level of sedation. The sedation persists 2 to 5
minutes after a single bolus and longer for patients receiving multiple
boluses, with a return to baseline within 10 to 15 minutes. This medication
has been associated with rates of clinically apparent respiratory depression
from 4.0% to 7.7% in ED PSA. As with similar agents, close ventilatory
monitoring is required. Propofol causes hypotension in critically ill
patients and should be used with caution in hemodynamically unstable
patients.
The combination of propofol and ketamine has also been described. It
has been shown to have decreased rates of recovery agitation than
ketamine alone, and less hypotension than propofol alone. It is likely that
the combination of agents can decrease the associated risk of adverse
events and potentiate the benefit of the drugs but that it must be tailored to
the needs to the individual patient.87,96
Etomidate is also frequently used for ED PSA.102 It is given as a single

5414
bolus of 0.1 to 0.3 mg/kg, with an onset of sedation in 30 to 60 seconds
and sedation lasting 7 to 10 minutes. It is not associated with hypotension
and is more commonly used when this is an issue; however, its use is
associated with myoclonic jerking in up to 25% of patients. This adverse
effect can complicate the procedure for which the patient has been sedated,
making it inferior to propofol for the sedation of healthy patients.
Etomidate, in single boluses of 0.3 mg/kg, has been shown to cause
transient adrenal suppression, but no significant changes in cortisol levels
occur, and the significance of this finding remains unclear. It has been
shown to cause less hypotension in severely ill patients requiring sedation
and is likely a better choice in these patients until they are stabilized
despite the unclear risk of adrenal suppression.

Evolving Emergency Department Pain Management

Practice
Pain management practices in the ED continue to evolve. The ACEP,
emergency medicine’s principal specialty organization, established its first
general policy statement regarding analgesic practices in 2004.103 Prior to
this, data from the National Hospital Ambulatory Medical Care Survey
showed that, from 1997 to 2001, there was an impressive 18% increase in
analgesic use in US EDs (from 47.2 to 56.2 mentions per 100 visits), with
marked increases in both NSAID agents and opioid analgesics.104
At the local level, adoptions of pain management guidelines and quality
improvement processes have demonstrated dramatic improvements in
practices. In one 3-site study, rates of ED analgesic treatment increased
from 54% to 84% over 1 year as a result of individual and group
feedback.105 In a study from one Swiss ED, educational programs and
guideline implementation led to marked increases in pain intensity
documentation, analgesic administration, reduction in pain intensity
scores, and improved patient satisfaction over a 4-month period.106
We do not know the reasons for the rapid evolution of ED pain
management practice. Policy and regulatory initiatives, institutional
quality improvement programs, increased attention to the opioid abuse
epidemic in the United States, pharmaceutical marketing campaigns,

5415
educational efforts, and new knowledge from basic and clinical research
are all likely to be influential factors. No matter the cause, emergency
medicine pain research is increasing at a rapid pace, and ED pain
management practices will continue to evolve.

Conclusion
Relieving pain and reducing suffering are primary responsibilities of
emergency medicine and much can be done to improve the care of ED
patients in pain. Emergency physicians and nurses continue to refine their
approach to the problem of pain, and in time, the current large amount of
variability in ED pain practices will no doubt lessen. Clinicians,
researchers, and policy makers continue to define specialty-specific
standards for emergency medicine pain practice in an effort to both
improve the management of pain in emergencies and to decrease the risk
to patients from the medications used. Ongoing quality improvement
initiatives, education, and research are essential to achieving these goals.

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35. Tamayo-Sarver JH, Hinze SW, Cydulla RK, et al. Racial and ethnic disparities in emergency
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44. Zechnich AD, Hedges JR. Community-wide emergency department visits by patients
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45. Beaudoin FL, Lin C, Guan W, et al. Low-dose ketamine improves pain relief in patients
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46. Maughan BC, Bachhuber MA, Mitra N, et al. Prescription monitoring programs and
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49. Todd KH. Pain and prescription monitoring programs in the emergency department. Ann
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50. Poon SJ, Greenwood-Ericksen MB, Gish RE, et al. Usability of the Massachusetts
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51. Greenwood-Ericksen MB, Poon SJ, Nelson LS, et al. Best practices for prescription drug
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52. Marco CA, Venkat A, Baker EE, et al. Prescription drug monitoring programs: ethical issues
in the emergency department. Ann Emerg Med 2016;68(5):589–598.
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54. Grover CA, Elder JW, Close RJ, et al. How frequently are “classic” drug-seeking behaviors
used by drug-seeking patients in the emergency department? West J Emerg Med
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55. Tanabe P, Hafner JW, Martinovich Z, et al. Adult emergency department patients with sickle
cell pain crisis: results from a quality improvement learning collaborative model to improve
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56. Tanabe P, Myers R, Zosel A, et al. Emergency department management of acute pain episodes
in sickle cell disease. Acad Emerg Med 2007;14(5):419–425.
57. Puri Singh A, Haywood C Jr, Beach MC, et al. Improving emergency providers’ attitudes
toward sickle cell patients in pain. J Pain Symptom Manage 2016;51(3):628.e3–632.e3.
58. Shapiro BS, Benjamin LJ, Payne R, et al. Sickle cell-related pain: perceptions of medical
practitioners. J Pain Symptom Manage 1997;14(3):168–174.
59. Pack-Mabien A, Labbe E, Herbert D, et al. Nurses’ attitudes and practices in sickle cell pain
management. Appl Nurs Res 2001;14(4):187–192.
60. Tanabe P, Martinovich Z, Buckley B, et al. Safety of an ED high-dose opioid protocol for
sickle cell disease pain. J Emerg Nurs 2015;41(3):227–235.
61. Tanabe P, Artz N, Mark Courtney D, et al. Adult emergency department patients with sickle
cell pain crisis: a learning collaborative model to improve analgesic management. Acad
Emerg Med 2010;17(4):399–407.
62. Todd KH, Sloan EP, Chen C, et al. Survey of pain etiology, management practices and patient
satisfaction in two urban emergency departments. CJEM 2002;4(4):252–256.
63. Steinberg PL, Nangia AK, Curtis K. A standardized pain management protocol improves
timeliness of analgesia among emergency department patients with renal colic. Qual Manag
Health Care 2011;20(1):30–36.
64. Miner JR, Moore J, Gray RO, et al. Oral versus intravenous opioid dosing for the initial
treatment of acute musculoskeletal pain in the emergency department. Acad Emerg Med
2008;15(12):1234–1240.
65. Neighbor ML, Baird CH, Kohn MA. Changing opioid use for right lower quadrant abdominal
pain in the emergency department. Acad Emerg Med 2005;12(12):1216–1220.
66. Motov S, Yasavolian M, Likourezos A, et al. Comparison of intravenous ketorolac at three
single-dose regimens for treating acute pain in the emergency department: a randomized
controlled trial. Ann Emerg Med 2017;70(2):177–184.
67. Safdar B, Dequtis LC, Landry K, et al. Intravenous morphine plus ketorolac is superior to
either drug alone for treatment of acute renal colic. Ann Emerg Med 2006;48(2):173.e1–
181.e1.
68. Hewitt DJ, Todd KH, Xiang J, et al. Tramadol/acetaminophen or hydrocodone/acetaminophen
for the treatment of ankle sprain: a randomized, placebo-controlled trial. Ann Emerg Med
2007;49(4):468.e2–480.e2.
69. Bijur PE, Kenny MK, Gallagher EJ. Intravenous morphine at 0.1 mg/kg is not effective for
controlling severe acute pain in the majority of patients. Ann Emerg Med 2005;46(4):362–
367.
70. Birnbaum A, Schechter C, Tufaro V, et al. Efficacy of patient-controlled analgesia for patients
with acute abdominal pain in the emergency department: a randomized trial. Acad Emerg Med
2012;19(4):370–377.

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71. Miner JR, Kletti C, Herold M, et al. Randomized clinical trial of nebulized fentanyl citrate
versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain.
Acad Emerg Med 2007;14(10):895–898.
72. Borland M, Jacobs I, King B, et al. A randomized controlled trial comparing intranasal
fentanyl to intravenous morphine for managing acute pain in children in the emergency
department. Ann Emerg Med 2007;49(3):335–340.
73. Shimonovich S, Gigi R, Shapira A, et al. Intranasal ketamine for acute traumatic pain in the
emergency department: a prospective, randomized clinical trial of efficacy and safety. BMC
Emerg Med 2016;16(1):43.
74. Yeaman F, Meek R, Egerton-Warburton D, et al. Sub-dissociative-dose intranasal ketamine
for moderate to severe pain in adult emergency department patients. Emerg Med Australas
2014;26(3):237–242.
75. Arhami Dolatabadi A, Memary E, Kariman H, et al. Intranasal desmopressin compared with
intravenous ketorolac for pain management of patients with renal colic referring to the
emergency department: a randomized clinical trial. Anesth Pain Med 2017;7(2):e43595.
76. Godwin SA, Burton JH, Gerardo CJ, et al. Clinical policy: procedural sedation and analgesia
in the emergency department. Ann Emerg Med 2014;63(2):247.e18–258.e18.
77. Green SM, Roback MG, Miner JR, et al. Fasting and emergency department procedural
sedation and analgesia: a consensus-based clinical practice advisory. Ann Emerg Med
2007;49(4):454–461.
78. Miner JR, Huber D, Nichols S, et al. The effect of the assignment of a pre-sedation target level
on procedural sedation using propofol. J Emerg Med 2007;32(3):249–255.
79. Miner JR, Burton JH. Clinical practice advisory: emergency department procedural sedation
with propofol. Ann Emerg Med 2007;50(2):182.e1–187.e1.
80. Miner JR, Driver BE, Moore JC, et al. Randomized clinical trial of propofol versus alfentanil
for moderate procedural sedation in the emergency department. Am J Emerg Med
2017;35:1451–1456.
81. Bellolio MF, Gilani WI, Barrionuevo P, et al. Incidence of adverse events in adults
undergoing procedural sedation in the emergency department: a systematic review and meta-
analysis. Acad Emerg Med 2016;23(2):119–134.
82. Miner JR, Bachman A, Kosman L, et al. Assessment of the onset and persistence of amnesia
during procedural sedation with propofol. Acad Emerg Med 2005;12(6):491–496.
83. Burton JH, Miner JR, Shipley ER, et al. Propofol for emergency department procedural
sedation and analgesia: a tale of three centers. Acad Emerg Med 2006;13(1):24–30.
84. Miner JR, Heegaard W, Plummer D. End-tidal carbon dioxide monitoring during procedural
sedation. Acad Emerg Med 2002;9(4):275–280.
85. Deitch K, Miner J, Chudnofsky CR, et al. Does end tidal CO2 monitoring during emergency
department procedural sedation and analgesia with propofol decrease the incidence of hypoxic
events? A randomized, controlled trial. Ann Emerg Med 2010;55(3):258–264.
86. Miner JR, Moore JC, Plummer D, et al. Randomized clinical trial of the effect of supplemental
opioids in procedural sedation with propofol on serum catecholamines. Acad Emerg Med
2013;20(4):330–337.
87. Miner JR, Moore JC, Austad EJ, et al. Randomized, double-blinded, clinical trial of propofol,
1:1 propofol/ketamine, and 4:1 propofol/ketamine for deep procedural sedation in the
emergency department. Ann Emerg Med 2015;65(5):479.e2–488.e2.
88. Green SM, Denmark TK, Cline J, et al. Ketamine sedation for pediatric critical care
procedures. Pediatr Emerg Care 2001;17(4):244–248.
89. Miner JR, Martel ML, Meyer M, et al. Procedural sedation of critically ill patients in the
emergency department. Acad Emerg Med 2005;12(2):124–128.

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 90. Deitch K, Chudnofsky CR, Dominici P, et al. The utility of high-flow oxygen during
emergency department procedural sedation and analgesia with propofol: a randomized,
controlled trial. Ann Emerg Med 2011;58(4):360.e3–364.e3.
91. Green SM, Roback MG, Kennedy RM, et al. Clinical practice guideline for emergency
department ketamine dissociative sedation: 2011 update. Ann Emerg Med 2011;57(5):449–
461.
92. Green SM, Roback MG, Krauss B, et al. Predictors of airway and respiratory adverse events
with ketamine sedation in the emergency department: an individual-patient data meta-analysis
of 8,282 children. Ann Emerg Med 2009;54(2):158.e4–168.e4.
93. Green SM, Roback MG, Krauss B; for Emergency Department Ketamine Meta-Analysis
Study Group. Laryngospasm during emergency department ketamine sedation: a case-control
study. Pediatr Emerg Care 2010;26(11):798–802.
94. Green SM, Sherwin TS. Incidence and severity of recovery agitation after ketamine sedation
in young adults. Am J Emerg Med 2005;23(2):142–144.
95. Green SM, Roback MG, Krauss B, et al; for Emergency Department Ketamine Meta-Analysis
Study Group. Predictors of emesis and recovery agitation with emergency department
ketamine sedation: an individual-patient data meta-analysis of 8,282 children. Ann Emerg
Med 2009;54(2):171.e4–180.e4.
96. Nejati A, Moharari RS, Ashraf H, et al. Ketamine/propofol versus midazolam/fentanyl for
procedural sedation and analgesia in the emergency department: a randomized, prospective,
double-blind trial. Acad Emerg Med 2011;18(8):800–806.
97. McQueen A, Wright RO, Kido MM, et al. Procedural sedation and analgesia outcomes in
children after discharge from the emergency department: ketamine versus
fentanyl/midazolam. Ann Emerg Med 2009;54(2):191.e4–197.e4.
98. Deitch K, Chudnofsky CR, Dominici P. The utility of supplemental oxygen during emergency
department procedural sedation and analgesia with midazolam and fentanyl: a randomized,
controlled trial. Ann Emerg Med 2007;49(1):1–8.
99. Godambe SA, Elliot V, Matheny D, et al. Comparison of propofol/fentanyl versus
ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency
department. Pediatrics 2003;112(1 pt 1):116–123.
100. Chun TH, Amanullah S, Karishma-Bahl D, et al. Comparison of methohexital and
pentobarbital as sedative agents for pediatric emergency department patients for computed
tomography. Pediatr Emerg Care 2009;25(10):648–650.
101. Miner JR, Biros M, Krieg S, et al. Randomized clinical trial of propofol versus methohexital
for procedural sedation during fracture and dislocation reduction in the emergency
department. Acad Emerg Med 2003;10(9):931–937.
102. Miner JR, Danahy M, Moch A, et al. Randomized clinical trial of etomidate versus propofol
for procedural sedation in the emergency department. Ann Emerg Med 2007;49(1):15–22.
103. Pain management in the emergency department. Ann Emerg Med 2004;44(2):198.
104. McCaig LF, Burt CW. National Hospital Ambulatory Medical Care Survey: 2002 emergency
department summary. Adv Data 2004;340:1–34.
105. Sucov A, Nathanson A, McCormick J, et al. Peer review and feedback can modify pain
treatment patterns for emergency department patients with fractures. Am J Med Qual
2005;20(3):138–143.
106. Decosterd I, Huqli O, Tamchés E, et al. Oligoanalgesia in the emergency department: short-
term beneficial effects of an education program on acute pain. Ann Emerg Med
2007;50(4):462–471.

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C H A P T E R 11 4
Pain Management in the Intensive
Care Unit
CURTIS N. SESSLER, KIMBERLY VARNEY GILL,
and KRISTIN MILLER

Pain, Analgesia, and Critical Illness

Pain is ubiquitous among critically ill patients, yet the nature of critical
illness and intensive care unit (ICU) care presents many unique challenges
to effective pain management.1–10 A central responsibility of all ICU
clinicians is to provide comfort and mitigate unpleasant sensations
including pain as well as anxiety, dyspnea, and other forms of
distress.11–17 Experts have provided guidance regarding managing pain in
the ICU, often within the paradigm of sedation and analgesia. In this
chapter, we focus on the unique aspects of pain and analgesia in the ICU
within the context of a comprehensive textbook on pain.11–14,17–20
ICUs are filled with patients who have suffered critical illness or injury
and the accompanying discomfort. Many patients have undergone surgery
or experienced trauma or burns and are likely to have pain as a direct result
of tissue injury and related management such as dressing changes and
wound care. Other patients have localized inflammation due to infection or
have neuropathies or other specific conditions that produce pain. The
majority of ICU patients undergo routine care which can contribute to
discomfort or frank pain. Such interventions include the presence of
indwelling tubes (i.e., nasogastric, endotracheal, bladder, and rectal tubes)
or vascular catheters that can induce pain during their insertion and in
some cases continue to produce discomfort by their mere presence.3–5,21,22
Even simple tasks that are routinely performed many times each day—
such as tracheal suctioning or turning of the patient from side to side—are
reported as painful by ICU patients.5,9,22,23

5422
 The nature of critical illness and ICU care can complicate various
aspects of pain management. For example, the sensation of pain may be
intensified by the concomitant anxiety, sleep deprivation, and
delirium.23–33 It is clear that all of these conditions are commonplace
among critically ill patients. Further, immobility and impaired
communication can intensify anxiety and perception of pain. Newer
integrated approaches to optimize patient comfort and hasten recover
comprehensively address analgesia as well as efforts to reduce anxiety yet
avoid oversedation, improve sleep quality, prevent delirium, speed
liberation from mechanical ventilation, and enhance rehabilitation and
mobility.34–40
Pain is often poorly recognized and quantified, further challenging
effective pain management.11,12 This can be the result of impaired
communication due to a reduced level of consciousness from sedative
medications or difficulty with phonation and movement due to oral tubes,
physical restraints, or paralysis. Although the presence of pain may be
inferred as a result of unexplained autonomic hyperactivity (i.e.,
tachypnea, tachycardia, or hypertension), these signs have many other
causes and thus are nonspecific for pain.11 Clinicians’ evaluation of
patients for possible pain include observing behaviors such as grimacing or
rigid body positioning, but these are less reliable as sedation
deepens.11,22,41–55 Overt agitated behavior, a not infrequent occurrence
among critically ill patients, is typically attributed to delirium, particularly
due to alcohol or sedative drug withdrawal, but can also be the result of
inadequately managed pain.56–63
Pharmacologic management of pain is more complex in the ICU than in
many other settings.11–14,17–20 The majority of ICU patients have organ
dysfunction. In particular, the utilization of many opioid and nonopioid
analgesics is impacted by the high prevalence of impaired hepatic
metabolism or renal clearance, problems with enteral or transdermal drug
administration, and concerns for drug interactions with the extensive list of
medications required for many ICU patients.64–67 Recognition and
amelioration of adverse effects of analgesics and other medications is often
more difficult because of ongoing organ dysfunction and concomitant
medical problems as well as the large number of medications utilized. In

5423
particular, the high prevalence of impaired gastrointestinal mobility from
opioids becomes far more than just the inconvenience and discomfort of
constipation and can impact administration of nutrition and enteral
medications; can worsen respiratory function; and can lead to additional
treatment, tests, and interventions.68 These many ICU factors elevate the
complexity of pain management.
In the ICU setting, opioid administration is often performed for
purposes beyond pure pain management, that of providing comfort and
tolerance of the ICU interventions along with sedative drugs—called
analgosedation. This approach relies on titration of both sedative-hypnotic
and opioid analgesic drugs to improve the patient’s tolerance of
mechanical ventilation and other aspects of the ICU environment and
routine ICU care. The target is comfort without oversedation and is often
best achieved with a balanced approach that allows selection of
medications that are preferred for a specific patient (e.g., organ
dysfunction or hemodynamic compromise) and can minimize adverse
effects of medications by using lower doses and potentially synergistic
effects.11–20,69–74 Some clinical trials have demonstrated better outcomes
when such an approach is used. Although titration of the opioid component
to a pain reduction target remains operative, the overall level of
consciousness and patient–ventilator interaction often influences the
dosing of both sedative and analgesic infusions. Thus, somewhat uniquely
to the ICU setting, “pain management” also encompasses management of
“analgosedation” and tolerance of mechanical ventilation and other ICU
interventions.
Successful management of pain, provision of comfort, and timely
recovery from critical illness are highly dependent on the
multiprofessional care team implemented in many ICUs. Pain management
in particular relies on the effective partnership between the treating
physician, the bedside nurse, and the clinical pharmacist. This includes
designing a treatment strategy that is patient focused with consideration of
the patient’s unique analgesic needs and factors like organ dysfunction that
influence management. Implementation is enhanced through standardized
approaches, order sets, guidelines, and other tools plus ongoing
communication and review. The comprehensive ICU team also includes

5424
physical therapists, nutritionists, respiratory therapists, and others who
contribute to missions of comfort and rapid recovery. Further, utilization
of expert consults from palliative care or pain management services can
make an important difference in selected patients. Accordingly, effective
pain management in the ICU brings the advantages, but also challenges, of
a team-based approach.34–40
A final consideration as to the unique aspects of pain management in the
ICU is that the physiologic consequences of untreated pain may be
particularly detrimental in critically ill patients who already have ongoing
shock, tissue injury, and organ failure producing a complex state of
physiologic disruption.75 Pain can cause neurohormonal derangements,
catecholamine release, stress response, cytokine production, and other
physiologic derangements. These and other pain-induced changes can
promote hypercoagulability, altered glucose control, myocardial ischemia,
hemodynamic compromise, immune system dysfunction, excessive
inflammation, ventilator asynchrony, and disrupted sleep.
There is strong motivation from multiple standpoints to effectively
detect and manage pain in a multiprofessional and patient-centered
approach. Some of these manifestations are listed in Table 114.1. The core
evidence-based recommendations directly related to pain and analgesia
from the Society of Critical Care Medicine (SCCM) are displayed in Table
114.2 and form the basis of management.11

TABLE 114.1 Systemic and Physiologic Consequences of Pain in

the Intensive Care Unit
Physiologic System and Effects
Immune: cytokines elaboration and leukocyte
dysfunction
Cardiovascular: increased adrenergic tone and
increased vascular resistance
Renal: activation of renin-angiotensin-
aldosterone axis
Endocrine: hormonal imbalance, especially
cortisol and insulin
Respiratory: restrictive physiology,
hyperventilation, lowered residual capacity
Psychological and neurologic: altered sleep
stage and serotonergic imbalance
Consequences
Decreased ability to fight infection and
hemodynamic instability
Increased myocardial oxygen demand, stress,
and ischemia; venous stasis
Water and sodium retention, anasarca
Hyperglycemia
Patient–ventilator asynchrony, atelectasis,
hypoxia, increased pneumonia risk
Depression, fatigue, psychosis, sleep
deprivation, anxiety

5425
 Hematologic: hypercoagulability and platelet Bleeding, thromboembolic disease
dysfunction

TABLE 114.2 2013 SCCM Pain, Agitation, and Delirium

Guidelines: Statements and Recommendations for Treatment of
Pain in the Intensive Care Unit (ICU)
ICU patients frequently experience pain at rest, with routine ICU care and in association with
devices and procedures (B).
Pain should be routinely monitored in all adult ICU patients (+1B).
The Behavioral Pain Scale and the Critical-Care Pain Observational Tool are the most valid
behavioral pain scales in medical, postoperative, or trauma (with the exception of brain injury)
adult ICU patients who are unable to self-report pain (B).
Vital signs may be used as a cue (+2C) but should not be used alone in the assessment of pain
(+2C).
Preemptive analgesia should be used in adult ICU patients prior to procedures (+2C),
including chest tube removal (+1C).
First-line therapy: intravenous opioids for nonneuropathic pain (+1C)
Consider nonopioid analgesics as adjunctive therapies to reduce opiates and related side
effects (+2C).
Treat neuropathic pain with gabapentin or carbamazepine (+1A).
Thoracic epidural anesthesia/analgesia should be considered for abdominal aortic aneurysm
postoperative patients (+1B) or patients with traumatic rib fractures (+2B).
Analgesia-first sedation should be used in mechanically ventilated adult ICU patients (+2B).
NOTE: The quality of evidence for each statement and recommendation was ranked as high (A),
moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or
weak (2) and either in favor of (+) or against (−) an intervention.

Evaluation and Monitoring of Pain in the Intensive

Care Unit
Effective pain management begins with the assumption that pain is
common among ICU patients and that caregivers should systematically
and repeatedly evaluate each patient for the presence of pain, its intensity,
and its characteristics.11–13,16,41 Unfortunately, research confirms that
caregivers tend to underrecognize pain and often fail to preemptively treat
pain.21 Accordingly, clinicians should err on the side of presuming pain is
present. Repeated assessment is desirable because conditions change over
time and pain management is more effective at an early stage than after
pain has become established and more severe.
Ideally, pain should be described in regard to location, duration, type,

5426
exacerbating and relieving factors, and intensity. Pain should be also be
considered by subtype—including somatic, visceral, and neuropathic—
because manifestations and management can be different.11,41 For
example, somatic pain is typically dull and aching, often localized, and
responds well to opioids and nonsteroidal anti-inflammatory drugs
(NSAIDs). In contrast, visceral pain is often cramping and colicky and
may respond to anticholinergic therapy, whereas the burning and shooting
neuropathic pain is often best treated with antidepressant and
anticonvulsant agents. Repeated and thorough evaluation helps to
determine the cause and to appreciate prior responses to therapy.
Because pain is a subjective interpretation by an individual, the ability
of that individual to communicate the presence and magnitude of pain is
important in guiding evaluation and management when possible.11,41
Many ICUs employ a strategy of daily interruption of sedation, even in
unstable sedated patients, and this brief period of greater awareness by the
patient presents an opportunity for communication about pain. Although
detailed verbal communication about the presence, intensity, and character
of pain is ideal, it is often not possible with ICU patients and the use of
simple tools can enhance communications of the presence and intensity of
pain. These simple tools, such as numerical rating scales and a series of
cartoon faces ranging from smiling to crying like the Wong-Baker FACES
scale, can facilitate communication via pointing or nodding by the
cognitively intact but nonverbal patient.42 A simple horizontal 0-to-10
numerical scale with enlarged font was judged to be feasible and valid in
one comparison of tools.43 Other techniques to improve the process of
self-reporting of pain include adding descriptive words to the numerical
scale, explaining the tool and correcting errors with each encounter,
providing needed glasses and hearing aids, and ensuring adequate time for
instructions and patient response.41 Use of a scale that incorporates
descriptive pictures, like the FACES scale, can help overcome language
barriers as well as mild cognitive dysfunction.
Many ICU patients are cognitively impaired, and self-reporting pain is
not feasible. For these patients, utilizing a structured evidence-based
approach to infer the presence and severity of pain based on observation
can be performed. Tools have been developed based on observed

5427
behaviors that have been correlated with self-reported pain and/or with
responses to noxious stimuli in prior research.9,21,44–46 Various
combinations of behaviors have been assembled into structured assessment
tools—most include facial expressions, body position and movement, and
patient–ventilator interaction. Contraction of facial muscles associated
with grimacing correlates particularly well with noxious stimuli.22 The
early work in pain assessment for noncommunicative ICU patients was
with infants and young children, resulting in the development of the
COMFORT Scale, the FLACC Observation tool, and others.41,76,77
Subsequently, a variety of pain assessment tools for nonverbal critically ill
adults have been developed, validated, and critically reviewed.11,41,47,48
Published pain observation tools for adults in the ICU care include the
Critical-Care Pain Observation Tool (CPOT); the Behavioral Pain Scale
(BPS); the Behavioral Pain Scale for non-intubated patients (BPS-NI); the
Nonverbal Pain Scale (NVPS); the Pain Behavioral Assessment Tool
(PBAT); and the Pain Assessment, Intervention, and Notation (PAIN)
tool.49–55 Additionally, the Adaptation to the Intensive Care Environment
(ATICE) tool incorporates facial grimacing as one of five components.78
Following comprehensive testing of psychometric properties and issues of
relevance and implementation, the CPOT (Table 114.3) and BPS (Table
114.4) scales were recommended in the 2013 guidelines as the most valid
and reliable behavioral pain scales for monitoring pain in adult medical,
postoperative, or trauma ICU patients who are unable to self-report and in
whom motor function is intact and behaviors are observable.11 Because
these tools all rely on behavioral responses to noxious events, their validity
can be influenced by other factors, particularly sedative medications.
Specifically, both scores of CPOT and BPS decrease and validity falls with
deepening sedation.50,55 Given the inexact nature of pain evaluation in
noncommunicative patients, investigators continue to explore new ways to
detect pain including detection of specific muscles during facial
movements like grimacing,22,79 and various measures of autonomic
response to nociceptive stimulation including heart rate variability,
pupillary dilatation reflex, and skin conductance.80,81

TABLE 114.3 The Critical-Care Pain Observation Tool (CPOT)

5428
 Indicator Description Score
Facial expression No muscular tension observed Relaxed, neutral 0
Presence of frowning, brow lowering, orbit Tense 1
tightening, and levator contraction
All of the above facial movements plus eyelid Grimacing 2
tightly closed
Body movements Does not move at all (does not necessarily Absence of 0
mean absence of pain) movements 1
Slow, cautious movements, touching or Protection
rubbing the pain site, seeking attention
through movements
Pulling tube, attempting to sit up, moving Restlessness 2
limb, thrashing, not following commands,
striking at staff, trying to climb out of bed
Muscle tension No resistance to passive movements Relaxed 0
Evaluation by Resistance to passive movements Tense, rigid 1
passive flexion Strong resistance to passive movements, Very tense or rigid 2
and extension of inability to complete them
upper
extremities
Compliance with Alarms not activated, easy ventilation Tolerating 0
the ventilator Alarms stop spontaneously ventilator or 1
(intubated Asynchrony: blocking ventilation, alarms movement 2
patient) frequently activated Coughing but
tolerating
Fighting ventilator
-OR-
Vocalization Talking in normal tone or no sound Talking in normal 0
(extubated Sighing, moaning tone or no 1
patient) Crying out, sobbing sound 2
Sighing, moaning
Crying out,
sobbing
Total, range 0–8
NOTE: Subscale scores are summed with a CPOT score ranging from 0 to 8. In one study, CPOT
>3 had sensitivity of 67% and specificity of 83% for self-reported pain in conscious ICU
patients.55
Republished with permission of American Association of Critical-Care Nurses from Gelinas C,
Fillion L, Puntillo KA, et al. Validation of the critical-care pain observation tool in adult patients.
Am J Crit Care. 2006;15(4):420–427; permission conveyed through Copyright Clearance Center,
Inc. Copyright © 2006 by the American Association of Critical-Care Nurses.

TABLE 114.4 The Behavioral Pain Scale (BPS)

Item Description Score
Facial expression Relaxed 1
Partially tightened (e.g., brow lowering) 2

5429
 Fully tightened (e.g., eyelid closing) 3
Grimacing 4
Upper limbs No movement 1
Partially bent 2
Fully bent with finger flexion 3
Permanently retracted 4
Compliance with Tolerating movement 1
ventilation Coughing but tolerating ventilation for most of the time 2
Fighting ventilator 3
Unable to control ventilation 4
NOTE: Three subscale scores are summed yielding a BPS score ranging from 3 to 12.
Reprinted with permission from Payen JF, Bru O, Bosson JL, et al. Assessing pain in critically ill
sedated patients by using a behavioral pain scale. Crit Care Med. 2001;29(12):2258–2263.

In addition to observable behaviors, pain is often accompanied by

readily observed physiologic responses such as tachycardia, hypertension,
and tachypnea. However, these changes in vital signs are inconsistently
associated with pain, are effected by many confounding factors (such as β-
adrenergic antagonists or other medications), and lack specificity for pain
with many other common causes including dyspnea, anxiety, and fever.55
Accordingly, 2013 guidelines recommend against the use of vital signs (or
observational pain scales that include vital signs) alone for pain assessment
in adult ICU patients.11 Clinicians should, however, regard unexplained
tachycardia, tachypnea, and hypertension as potential clues to the presence
of pain, prompting further pain assessment.11 Other potentially useful
approaches include assessing the patient’s response to a trial of analgesic
medication41 and use of surrogate (such as family members) report.2 It
should be considered, however, that surrogates may lack reliability and
accordingly should not be the sole source for monitoring.82,83

Managing Pain and Analgesia in the Intensive Care

Unit
The provision of adequate pain control is a core practice for all ICU
patients. Ensuring pain relief to patients not only relieves human suffering
but additionally mitigates the negative short- and long-term physiologic
effects caused by untreated pain. Unfortunately, pain remains inadequately
treated in many patients. Some of the barriers to providing adequate pain

5430
relief include difficulty with accurate pain assessment, a lack of
understanding of dose and dose titration of opioids, presence of adverse
effects from opioids, and variations in attitudes toward use of opioids
(particularly in patients with an underlying opioid use disorder).11,12,17,64
Increased education on use of pain assessment tools and a comprehensive
understanding of the pharmacokinetic and pharmacodynamic properties of
various pain medications may help improve overall outcomes with regard
to the treatment of pain in hospitalized patients. Structured approaches and
aids such as order sets and guidelines can reduce variability in practice.
A considerable challenge during management is balancing adequate
pain control against the adverse effects of medications, particularly
opioids, in a diverse ICU patient population. Clinicians should consider a
multimodal approach to pain control, as some pain may not be responsive
to opioid therapy.84 Proposed opioid-sparing approaches include
prioritizing intermittent opioid boluses over continuous infusions when
possible, using patient-controlled analgesia when appropriate, and using
nonopioid medications when clinically feasible (i.e., low-dose ketamine,
α2 agonists such as clonidine and dexmedetomidine, acetaminophen,
NSAIDs, and local treatments such as lidocaine patches).11,12 Adjuvant
nonpharmacologic therapies (i.e., music therapy, relaxation techniques)
also play a complementary role and should be considered to help decrease
the use of opioids.11,12,17,85–87 Pharmacologic and other approaches are
discussed in detail in the following section, along with approaches to
integrate analgesic practices with related care.

PHARMACOLOGIC TREATMENT OF PAIN IN THE

INTENSIVE CARE UNIT: PARENTERAL OPIOIDS
The objective of administering opioids in the ICU is to improve patient
comfort and outcomes for critically ill patients. The opioid class is
considered first-line therapy for ICU patients experiencing nonneuropathic
pain.11,12 This class of medications acts primarily on the μ-opioid receptor
to provide analgesia. Opioid receptors are found in the central nervous
system within the locus ceruleus, ventral medulla, and substantia
gelatinosa of the dorsal horn; they are also found in peripheral tissue of
neural and nonneural origin.66 Most opioids have lipophilic properties and

5431
undergo extensive first-pass metabolism, allowing for rapid transference
across cell membranes and rapid onset of activity. Important variations in
pharmacokinetics and dynamics exist between individual opioids (i.e.,
drug metabolism, drug interactions, protein binding, lipophilicity, adverse
effects) as well as with individual physiologic conditions (i.e., cirrhosis,
renal disease, opioid tolerance, older age, genetic polymorphism). These
characteristics should be thoughtfully considered when choosing and
titrating an opioid medication.88
The impact of the adverse effects of opioids on clinical outcomes in the
ICU is becoming increasingly recognized.11,12,17 Examples of adverse
effects of opioids include respiratory depression which may delay time to
extubation, development of constipation or ileus causing delays to
nutrition goals and impairing ventilation and oxygenation, altered mental
status including oversedation that can delay progression to liberation from
mechanical ventilation, mobility and strength, and the potential for opioid
withdrawal or dependence if receiving opioids for a prolonged period of
time.
Opioids, like other medications administered for prolonged periods, can
manifest protracted durations of effect. Analgesia and sedation can persist
for days to weeks after sustained infusions are discontinued, and it is
common for patients with hepatic or renal disease to experience
oversedation. Evidence-based therapeutic recommendations favor bolus
dosing and daily interruption of sedative and analgesic medications except
for the dying and those with uncontrolled pain.11,12
No specific opioid agent has been demonstrated to be preferable in all
ICU patients or across all clinical entities. Selection of initial analgesic
therapy should be based on individual patient characteristics and
knowledge of prior opiate exposure, experience, and side effects, when
available. As is the case for all medications first introduced to the patient
in the ICU, it is important to de-escalate opioid doses in a fashion that does
not promote withdrawal symptoms but uses the lowest effective dose
aiming for transition to nonopioid agents if possible. The devastating
impact of the ongoing opioid abuse epidemic certainly provides strong
motivation for vigilance in opioid de-escalation.

5432
Fentanyl
Over the last 20 years, fentanyl has supplanted morphine as the most
commonly used analgesic in adult ICUs in the United States and is
commonly used throughout the world.89–91 Fentanyl is a potent opioid
from the phenylpiperidine class with an onset of action of 1 to 2 minutes
and a short duration of action when used in intravenous (IV) bolus form in
healthy individuals. It is highly lipophilic and highly protein bound.
Fentanyl exhibits a three-compartment distribution model, distributing
readily into both muscle and fat tissue. Prolonged IV fentanyl infusions
(i.e., >7 days) have led to protracted clearance times and delayed
awakening.92 Fentanyl is devoid of the histamine release seen upon
initiation of morphine and therefore is recommended over morphine for
patients who are hemodynamically unstable. Clinicians should still use
caution in hypotensive patients; however, as studies have demonstrated
hypotension associated with fentanyl use, particularly when fentanyl is
given in conjunction with other sedatives or when given rapidly in an IV
bolus form.93
Fentanyl undergoes hepatic metabolism via the cytochrome P450 3A4
isoenzyme, and potential for drug interactions is high causing either
inhibition or induction of fentanyl clearance. Fentanyl has a high hepatic
extraction ratio; therefore, clearance will be more affected by blood flow
through the liver than by intrinsic liver function.65 Accumulation of the
parent drug can occur in patients with cirrhosis, and monitoring for
oversedation is recommended.65 The presence of chest wall rigidity has
been described frequently with fentanyl in the pediatric population; it has
been reported as a rare but significant adverse effect in adults.88
Synthetic opioids from the phenylpiperidine and diphenylheptane
classes (i.e., fentanyl, methadone, meperidine, remifentanil, tramadol)
exhibit a dose-related increase in norepinephrine release from sympathetic
nerve endings and inhibition of neuronal uptake of norepinephrine. These
opioids also block reuptake of serotonin and have serotonin receptor
agonist activity. This increase in central norepinephrine and serotonin
levels can thereby predispose a patient to dangerous reactions if these
opioids are administered with serotonergic agents (i.e., antidepressants) or
monoamine oxidase inhibitors (i.e., linezolid).92,94–98 Reactions include

5433
serious autonomic and neurologic changes, such as hypertension,
tachyarrhythmias, severe hyperpyrexia, spontaneous or inducible clonus,
and coma; death has been reported in severe cases. In cases of drug
overdose from a serotonergic agent or monoamine oxidase inhibitor, or if
there are concerns for serotonin syndrome, certain opioids including
fentanyl should be avoided.99
These drug interactions need careful consideration if a patient requires
an opioid for acute pain control, along with reinitiation of the outpatient
antidepressant to avoid withdrawal. Therapeutic options may include
starting a lower dose of the serotonergic antidepressant, although this may
not prevent withdrawal from the antidepressant, or choosing an alternative
to fentanyl (i.e., hydromorphone, morphine, nonopioids). The combination
of a monoamine oxidase inhibitor with fentanyl or tramadol should be
avoided altogether due to a high risk and severity of adverse events.
Critical care guidelines recommend the choice of opioid be based on
specific drug and individual patient characteristics.11,12 Despite the
aforementioned concerns with variable kinetics and drug interactions in a
critical care patient, fentanyl has become the most commonly used opioid
in adult ICUs, likely due to its quick onset of action, lack of active
metabolites, and guideline recommendation over morphine for the
hemodynamically unstable patient.11 Clinicians should familiarize
themselves with the pharmacokinetics and dynamics of fentanyl, as it
continues to be highly utilized in adult ICUs.

Hydromorphone
Most studies reporting use of IV hydromorphone infusions in the acute
adult ICU setting are retrospective or observational in nature. Short- and
long-term effects of hydromorphone infusions have not been well
described in the adult ICU literature. Although fentanyl is generally the
recommended opioid of choice in the acute adult ICU setting, clinicians
may opt to use hydromorphone over fentanyl for various clinical scenarios
including prior chronic outpatient use of hydromorphone, tachyphylaxis to
fentanyl, better pain control with hydromorphone over fentanyl, and the
need to administer a serotonergic agent or a monoamine oxidase inhibitor
concomitantly.

5434
 When administered IV, hydromorphone has an onset of activity of 5 to
10 minutes and a duration of activity of 3 to 4 hours. Hydromorphone is
only 10% to 20% protein bound (because it undergoes phase 2 hepatic
glucuronidation), has less potential for metabolically based drug
interactions, and has more reliable clearance in hepatic failure.
Glucuronidation of hydromorphone produces the metabolite
hydromorphone-3-glucuronide (H3G). The H3G metabolite is devoid of
analgesic activity; however, it maintains neurotoxic effects such as
cognitive dysfunction, agitation, confusion, hallucinations, tremors,
clonus, and seizures.100–102 As glomerular filtration rate (GFR) declines,
H3G accumulates up to fourfold the initial concentration. Occurrence of
neurologic toxicities was seen in approximately 20% of patients with GFR
<60 mL per minute in a study of palliative care patients with chronic renal
insufficiency.28 Starting doses of hydromorphone should be adjusted for
renal dysfunction, and patients should be closely monitored for signs of
neurotoxicity if receiving high doses or continuous infusions of
hydromorphone in the presence of renal failure. Hemodialysis clears
hydromorphone; however, close monitoring of neurotoxic effects should
still be observed for patients on dialysis.

Morphine
Morphine has historically been the opioid of choice for acute pain and is
still commonly used in adults ICU patients around the world.103 Morphine
is a low-cost medication with effective analgesic and euphoric effects,
making it an attractive alternative in many acute clinical scenarios. Critical
care guidelines recommend morphine as an acceptable first-line agent for
pain in the ICU but advise that morphine may cause hypotension due to
systemic release of histamine.11 Both animal and human studies have
demonstrated significant histamine and nitric oxide release with morphine,
with subsequent decreases in systemic vascular resistance, bronchospasm,
and urticaria.104
Morphine is metabolized in the liver to morphine-3-glucuronide (M3G)
and morphine-6-glucuronide (M6G), both of which are subsequently
cleared by the kidneys. Similar to the hydromorphone metabolite H3G,
M3G does not have analgesic activity but can cause severe neurotoxic

5435
symptoms such as cognitive dysfunction, tremors, and seizure activity.105
However, the M6G metabolite is 2 to 8 times more potent than morphine
as an analgesic.106,107 These metabolites can exhibit prolonged effects in
patients with renal dysfunction and in patients receiving dialysis; therefore,
scheduled dosing and continuous infusions are not recommended in those
settings.105 In critically ill patients, the altered protein binding resulting
from malignancy, renal impairment, and hepatic failure may also alter
morphine pharmacokinetics and make dosing titration challenging.100

Remifentanil
Remifentanil is a selective μ-opioid receptor agonist approved for use in
anesthesia induction and maintenance that may have advantageous
properties for ICU care. The novelty in this agent, in contrast to fentanyl,
is that remifentanil is metabolized by multiple ubiquitous esterases, and its
half-life is not known to be prolonged by critical illness nor organ
dysfunction.108,109 Due to its pharmacokinetic properties, this agent has a
terminal half-life of less than 30 minutes and may reduce the incidence of
prolonged sedative complications seen with continuous infusions of other
opiates. Short-duration studies demonstrate reduced duration of
mechanical ventilation when this agent is compared to other opiates.110–112
Remifentanil can cause bradycardia and hypotension, potentially limiting
its use in the ICU. It has been used in traumatic brain injury and
neurosurgical settings with favorable effects on neurologic function
assessment and a dose-dependent reduction in coughing associated with
endotracheal suctioning. Concern remains, however, that the rapid offset
of this agent may lead to withdrawal and agitated behavior.113–115 In one
study, remifentanil was associated with a higher rate of moderate or
rebound pain upon cessation of a 72-hour infusion compared to fentanyl
(33% vs. 9%).73 There was no difference in mean extubation time in this
short-term study.73 Other published reports suggest remifentanil may be
associated with more rapid recovery from respiratory failure. In one
randomized controlled trial (RCT), patient who received remifentanil had
shorter duration of mechanical ventilation (3.9 vs. 5.1 days).74 In a 2017
meta-analysis of 23 RCTs of adult mechanically ventilated ICU patients,
remifentanil was associated with shorter duration of mechanical

5436
ventilation, shorter time to extubation after sedation cessation, and shorter
ICU length of stay (LOS).116

PHARMACOLOGIC TREATMENT OF PAIN IN THE

INTENSIVE CARE UNIT: ADJUVANT THERAPY
Ketamine
Ketamine has been used for decades in bolus IV form for procedural
sedation and analgesia, rapid sequence intubation, and brief operating
room (OR) cases.117 It is a well-established anesthetic agent and produces
a qualitatively unique state referred to as “dissociative anesthesia.” This
dissociative anesthesia has been described as having a spectrum of effects,
including hypnosis at lower doses, deep sedation and coma with higher
doses, potent antinociceptive effects, increased sympathetic tone, and
intact respiratory and airway tone. Added benefits include maintenance of
normal gastrointestinal motility and less respiratory depression compared
to opioids. At the bedside, these clinical effects could prove beneficial for
unstable ICU patients and has prompted increased interest in sustained
infusion ketamine in the ICU setting.118
Ketamine provides these effects via multiple mechanisms including
blockade of the N-methyl-D-aspartate (NMDA) channels, neuronal
hyperpolarization, δ- and μ-opioid agonism and opioid potentiation, effects
on the nitric oxide guanosine monophosphate system, reduction in
cholinergic modulation, and central release of dopamine and
noradrenaline.119 Ketamine has a large volume of distribution due to its
lipophilic properties but is not highly protein bound. It has a quick onset of
action (<5 minutes) and a short duration of activity in bolus form (5 to 15
minutes depending on dose). Hepatic and renal dysfunction can cause
accumulation and prolong ketamine’s duration of activity.
Emergence from the dissociative effect of ketamine can illicit reactions
such as hallucinations, agitation, confusion, and delirium. This emergence
reaction may be mitigated by giving a benzodiazepine prior to ketamine
boluses or upon discontinuation of continuous ketamine infusions.
Because ketamine is a sympathomimetic producing increased levels of
circulating dopamine and norepinephrine, ketamine should be avoided in
patients with concomitant cardiovascular disease or myocardial infarction.

5437
Ketamine may also increase pulmonary vascular pressures and therefore
should be used with caution or avoided in this patient population.
Reports of prolonged ketamine use (>24 hours) in the ICU are limited to
a few small studies.117,118 The optimal dose, duration, monitoring
parameters, and how ketamine fits into the armamentarium of medications
used for analgesia and sedation in the adult ICU remain unclear. Reported
ketamine doses described for use in the ICU vary but generally range from
0.05 mg/kg/hour to 0.4 mg/kg/hour, with a maximum of 1.2 mg/kg/hour
when used for severe pain.11,118 Potential benefits of ketamine include
additional pain control (opioid sparing), reduced airway resistance,
increased lung compliance, minimal effect on respiratory drive at low to
moderate doses, and intact gastrointestinal motility.

Methadone
Methadone is a unique analgesic with multiple mechanisms of action
which contribute to its antinociceptive effects. These mechanisms are
centrally mediated through agonism at the μ-opioid receptor, antagonism
at the NMDA receptor, and inhibition of serotonin and norepinephrine
reuptake.120 The primary indications for use of methadone include chronic
pain and prevention of opioid withdrawal. Using methadone for acute pain
is challenging secondary to the need for slow and gradual uptitration every
2 to 3 days. More frequent titration can lead to higher than expected drug
levels with respiratory depression and oversedation as the drug gradually
reaches steady state.
Methadone is highly lipophilic leading to its relatively quick onset of
action, a “drug-depot” effect throughout the tissues, and an extended half-
life. Methadone is highly bound to plasma proteins, in particular to α1-acid
glycoprotein. The dosage forms for methadone include oral tablets,
suspension, and an IV formulation. The potency of the IV dose is
approximately twice that of the oral dose. There are multiple
considerations when using methadone in a complex ICU setting.
Methadone undergoes hepatic clearance; therefore, accumulation can
occur in acute or chronic liver dysfunction and lower doses should be
used. It is a major substrate of enzymes CYP 3A4 and 2B6 and a minor
substrate of CYP 2D6, 2C9, and 2C19; thus, medication profiles should be

5438
closely scrutinized for multiple drug interactions. Concern for QTc
prolongation exists for methadone, which can be problematic in an ICU
setting where other risk factors for QTc prolongation are often present
(multiple medications which prolong QTc, electrolyte abnormalities,
underlying cardiac disease). Common medications which will increase
methadone levels, thereby increasing risk for QTc prolongation and
serotonin syndrome, include azoles, macrolides, antipsychotics, and
antidepressants. The U.S. Food and Drug Administration (FDA) has issued
a boxed warning for the use of methadone with benzodiazepines, as this
combination has resulted in significant respiratory depression, profound
sedation, coma, and death. If using methadone in the ICU, an
electrocardiogram should be routinely monitored and electrolytes such as
potassium, magnesium, and calcium be maintained within the normal
range.120–122 Patients admitted to ICU from home while receiving chronic
methadone treatment and patients in opioid withdrawal may necessitate
initiation of methadone in the hospital or ICU—but with significant
caution.

Other Analgesics and Adjuvant Agents

Other agents may have a role in the ICU, but many possess properties that
limit their utility in critical care settings. Meperidine is associated with
neuroexcitation due to a metabolite, normeperidine potentially producing
seizures, and thus is rarely used in the ICU setting.11,12 It has been used in
the short term for shivering associated with general anesthesia or to abate
drug-induced rigors. Meperidine should not be given for more than 1 day
or at a cumulative dose over 600 mg. Codeine is converted to morphine in
order to be active, but a proportion of the population lack the necessary
enzymatic mechanism. Oxycodone is pharmacologically similar to
morphine but is only available in oral preparations. Oxycodone, along with
hydrocodone, have been associated with a high abuse potential in the
United States.123 Consideration for the patient’s medical and social history
(i.e., history of opioid abuse) should be taken into account upon initiation
of these medications.
Ketorolac is an IV nonsteroidal anti-inflammatory medication that may
be useful for anti-inflammatory effects but produces gastrointestinal

5439
toxicity and increases the risk for gastrointestinal bleeding that limits its
use to less than 5 days at a time or not at all in ICU patients already at risk
for bleeding. Corticosteroids and adenosine may have opiate-sparing
effects as adjuvant therapy but have not been evaluated in the ICU.
Lidocaine has also been used as an effective adjuvant for complex or
neuropathic syndromes but may be limited in the ICU due to its
arrhythmogenic properties.124 Acetaminophen is a weak analgesic that
carries the risk of hepatotoxicity with chronic use that similarly restricts its
utility in the ICU.
Clonidine is an α2-receptor agonist that provides mild sedation and mild
analgesia but is an antihypertensive and can cause hypotension. Its cousin,
dexmedetomidine, is a selective α2-receptor agonist with sedative
properties similar to benzodiazepines and propofol but, in contrast to other
sedatives, has analgesic properties and can be opioid sparing, is
sympatholytic potentially producing prominent bradycardia as well as
hypotension at higher doses, is associated with a more alert state relative to
anxiolytic properties, and has minimal effect on respiratory drive.125,126 It
does not bind γ-aminobutyric acid (GABA) receptors. In a meta-analysis
of 24 RCTs comparing dexmedetomidine to alternative sedative drugs,
ICU LOS was shorter with dexmedetomidine, whereas duration of
mechanical ventilation was not significantly different.127 Clinical trial
results suggest that when compared directly to midazolam,
dexmedetomidine may be associated with lower prevalence of delirium.128
Anticonvulsants (i.e., gabapentin, carbamazepine) are recommended in
guidelines in combination with opioids for confirmed neuropathic pain.11
However, anticonvulsants have not been studied extensively in the ICU
population, and there is a potential for significant adverse effects and drug
interactions, requiring close monitoring and follow-up. If the patient is
discharged home on an anticonvulsant for neuropathic pain, close follow-
up should be performed by the outpatient provider.

NONPHARMACOLOGIC MANAGEMENT OF PAIN IN

THE INTENSIVE CARE UNIT
Nonpharmacologic modalities are incompletely studied and infrequently
used in the ICU but have the potential to improve pain management.11,12

5440
Complementary therapies include distraction therapies, behavioral
modification, touch therapy, meditation, music therapy, acupuncture or
acupressure, and massage, among others. Simply providing information
can be beneficial. These approaches are generally safe, easy to provide,
and inexpensive; however, evidence of benefit sufficient to justify routine
use is weak, and their true impact on pain should not be
overestimated.85–87

REGIONAL ANESTHETIC APPROACHES TO PAIN IN

THE INTENSIVE CARE UNIT
Regional anesthesia and analgesia (RAA) includes continuous epidural
analgesia and/or anesthesia (central neuraxial techniques) and continuous
peripheral nerve or plexus block. These techniques are reviewed in detail
in Chapter 52 and will only be commented on briefly here. RAA
techniques provide medication delivery in close proximity to the spinal
cord or nerves and thus can result in parenteral opioid sparing, which is
associated with less respiratory depression and gastrointestinal
hypomotility, and other benefits. These techniques do, however, introduce
new issues related to needle and catheter placement and maintenance as
well as physiologic derangements related to local anesthetic block and
epidural drug administration. Critically ill patients are probably at higher
risk for RAA-related complications due to a higher incidence of
coagulopathy, thrombocytopenia, sepsis, and hemodynamic instability.
Utilization of RAA techniques in the ICU setting is largely limited to
surgical patients who are postoperative or injured. The availability of and
success with these techniques is probably closely tied to cumulative
experience and expertise of local experts. Peripheral nerve blocks can be
useful for anatomically localized pain such as limb injury or operation, but
there are few RCTs in ICU patients on which to base recommendations.
The largest body of evidence is related to epidural techniques but even that
is quite limited. Recommendations regarding RAA published in the 2013
SCCM guidelines were limited by availability of high-level data for ICU
patients, but recommendations were provided in several specific
scenarios.11 Thoracic epidural anesthesia and analgesia for postoperative
analgesia in patients with abdominal aortic surgery received a strong

5441
recommendation as superior to IV opioids.129 High-level evidence was
also available to compare lumbar epidural analgesia to IV opioids in the
same population but no benefit was demonstrated, and RAA was not
recommended.130 ICU patients with traumatic rib fractures had superior
pain and fewer cases of pneumonia when treated with thoracic epidural
analgesia than IV opioids but experienced more hypotension, and this form
of RAA was endorsed with a weak recommendation for managing pain
from traumatic rib fractures.131,132 There was insufficient evidence to
support RAA in any other ICU clinical setting including after thoracic
operations and nonvascular abdominal operations and for medical ICU
patients.11

Integrated Analgesia Management in the Intensive

Care Unit
Pain management and analgesia is a central theme in the comprehensive
care of the critically ill patient. The key concepts supported by published
evidence and recommended by experts (see Table 114.2) form the
framework of integrated analgesia management. First, pain should be
routinely monitored in all adult ICU patients, using behavioral pain scales
in those who are unable to self-report. Second, preemptive analgesia
should be used prior to procedures because it is more effective to prevent
pain than to control it once it has developed. Third, analgesia-first sedation
(analgosedation) should be used in mechanically ventilated adult ICU
patients. Fourth, IV opioids are first-line therapy for nonneuropathic pain,
but consider nonopioids analgesics to reduce opioid dosage and side
effects, and treat neuropathic pain with gabapentin or carbamazepine.11
The following sections will provide additional detail about using
combination therapy with opioid analgesics and sedative-hypnotic agents
with emphasis on analgesia-first sedation (analgosedation), followed by
discussion of the role of analgesia in comprehensive care that integrates
management of analgesia, sedation, delirium mitigation, liberation from
mechanical ventilation, and mobility and rehabilitation.

ANALGOSEDATION IN THE INTENSIVE CARE UNIT

5442
Analgesic and sedative drug therapy of critically ill, mechanically
ventilated patients should focus on careful selection and titration of drugs
to achieve optimal patient comfort while avoiding the adverse impact of
excessive or unnecessarily prolonged sedation. The use of structured
approaches to sedation and analgesia via algorithms and protocols has
achieved a prominent place in ICU practice. There are several common
themes. One theme is to focus first on analgesia, as discussed earlier. The
2013 guidelines suggest that analgesia-first sedation be used in
mechanically ventilated adult ICU patients.11 Asking first about pain,
before the patient has been sedated and cognitively impaired, is
advantageous. Additionally, several RCTs have demonstrated analgesia-
based sedation to be associated with shorter duration of mechanical
ventilation in comparison to hypnotic-based sedation.74,109,133 Strom et
al.69 randomized mechanically ventilated adult ICU patients to bolus
morphine (analgesia-based, limited sedation) versus morphine plus
propofol for the first 48 hours and then midazolam (sedation + analgesia)
and found shorter duration of mechanical ventilation and ICU LOS but
threefold more agitation when sedative drugs were minimized.
A second major theme is to tailor the sedation to the specific patient,
including medication selection based on sedation goals (such as rapid
arousal), avoidance of side effects (such as hypotension), and
consideration of elimination issues (such as avoiding midazolam in a
patient with impaired renal function). In addition to the opioid analgesic
medications discussed previously, a variety of sedative drugs have a role in
ICU sedation management. However, there is emerging evidence appears
to favor using propofol or dexmedetomidine in preference to
benzodiazepines in patients for whom continuous infusion sedation is
needed.11 A meta-analysis limited to moderate- or high-quality RCTs
demonstrated slightly longer ICU LOS with benzodiazepines in
comparison to propofol or dexmedetomidine.127 Several studies deserve
additional comment. A multicenter RCT comparing dexmedetomidine to
midazolam demonstrated that dexmedetomidine was associated with
shorter time to extubation, lower prevalence of delirium, and fewer
infections but no difference in ICU LOS, mortality, or sedation quality.128
In the two phase-3 multicenter RCTs that compared dexmedetomidine to

5443
midazolam, or propofol, patients randomized to dexmedetomidine had
shorter duration of mechanical ventilation than with midazolam but not
with propofol.134 Patient interaction (communication, arousability,
cooperation) was better with dexmedetomidine than with either other
agent, but hypotension and bradycardia were more common.
Dexmedetomidine may offer advantages for managing agitation or
hyperactive delirium, particularly that related to alcohol withdrawal.135–138
Propofol, the most widely used sedative agent in the United States,89 binds
GABA and other receptors and produces sedative-hypnotic effects similar
to benzodiazepines but no analgesic effects. It has rapid onset and offset of
action but has the disadvantages of producing hypotension and depressed
respiratory drive.139 Compared to benzodiazepines, propofol is associated
with shorter duration of mechanical ventilation and shorter ICU LOS.140
Another theme is to strive for a light level of consciousness and to avoid
accumulation of medications and their active metabolites, thus reducing
the likelihood of delayed awakening. This approach is strongly
recommended in the 2013 guidelines11 based in part on studies like those
of Strom et al.69 The underlying rationale for this approach arises from the
observation that continuous IV sedation and analgesia is associated with
delayed recovery from respiratory failure and longer LOS.141 Although a
variety of sedation management strategies have been demonstrated to
shorten the duration of mechanical ventilation, the most robust data
supports the use of a sedation protocol or the implementation of daily
interruption of sedation. Strategies that successfully promote a more alert
state have been associated with less medication use and accompanying
costs, less delirium, fewer tests for altered mental status, shorter duration
of mechanical ventilation, fewer tracheostomies, and shorter time in the
ICU and hospital.11,69,70,142–155 Abrupt withdrawal of sedative (and
sometimes analgesic) medications is accompanied by severalfold increases
in circulating catecholamines as well as tachycardia and hypertension, but
no evidence of triggering cardiac ischemia.156 Daily interruption of
sedation is also not followed by psychological complications like
posttraumatic stress disorder.157 Patients who should probably not undergo
daily interruption of sedation includes those with active seizures, alcohol
withdrawal, worsening agitation, neuromuscular blockade, acute

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myocardial ischemia, or elevated intracranial pressure.158

ANALGESIA AS A COMPONENT OF COMPREHENSIVE

BUNDLED INTENSIVE CARE UNIT CARE
Over the past decade, multiple RCTs have demonstrated the value of
linking strategies for managing analgesia and sedation in ICU patients with
related components of patient care including weaning and liberation from
mechanical ventilation, reducing the prevalence and duration of ICU
delirium, and promoting mobility and early rehabilitation. The improved
outcomes associated with linking interruption of sedation (or spontaneous
awakening trial [SAT]) with testing of the potential for ventilator
liberation (spontaneous breathing trial [SBT]),158 so called “wake up and
breathe,”159 illustrated the value of such an approach. Addition of early
mobility and exercise to SAT and SBT has further improved outcomes
including less delirium and more rapid recovery.160 Research and
experience has shown that when incorporating these components
collectively as a “bundle,” the patient has better outcomes, including
decreased ventilator days, decreased incidence of delirium, and shortened
hospital LOS.34–40 A crucial aspect of improving patient care revolves
around successfully disseminating and implementing the results of
compelling research findings through knowledge translation.
The ABCDEF approach (http://www.iculiberation.org) provides an
effective framework for patient-centered integrated care, with the
components depicted in Table 114.5.34,35 It is no surprise that a critical
part of the ABCDEF bundle is “A,” which stands for assessing,
preventing, and treating pain. The ABCDEF bundle also incorporate other
components that are relevant to the treatment of pain, such as “C” (choice
of sedating agent), not only focusing on analgosedation, to ensure pain is
controlled, but also recognizing the potential need for short-acting
sedatives as adjunctive agents to provide sedation, assisting in minimizing
potential adverse side effects of opiate-only sedation. In addition, the
importance of daily delirium screening (“D” in the ABCDEF bundles),
which may be directly related to sedation choice, is emphasized in the
ABCDEF bundles. Furthermore, the many benefits of early mobilization
(“E” in the ABCDEF bundles) are also a treatment and pain preventative

5445
tool in itself for ICU-related pain, as the pain associated with immobility is
a debilitating phenomenon that is often underrecognized. Collectively, one
could argue that all the components of the ABCDEF bundle are either
directly or indirectly intertwined and interrelated to pain in the ICU,
including the direct assessment and anticipation of pain, the pain
associated with endotracheal tubes that may be able to be removed sooner
with daily awakening and breathing trials, or the pain that accompanies
immobility. Therefore, it is imperative that a multimodal, interdisciplinary
group become familiar with these guidelines and implementation tools that
collectively represent best practice in intensive care medicine.

TABLE 114.5 The ABCDEF Bundle

Each letter of the ABCDEF bundle represents patient-centered, best practice in critical care:
A: assessing, preventing, and managing pain
B: both spontaneous awakening and breathing trials
C: choice of analgesia and sedation
D: assessing, preventing, and managing delirium
E: early mobility and exercise
F: family engagement and empowerment

Pain and Analgesia at the End of Life in the Intensive

Care Unit
Unfortunately, critically ill patients die in the ICU, and in some instances,
the realization that the end of life is imminent occurs when the patient is
receiving life-sustaining interventions such as vasopressors, mechanical
ventilation, dialysis, and other life-support devices. The presence of pain,
dyspnea, and other unpleasant sensations is not uncommon in the end-of-
life setting, particularly with existing invasive ICU interventions, and
achieving relief from distress becomes of paramount importance. The
principles for pain management at the end of life are discussed in detail in
Chapter 109.
In many such cases, the patient has ongoing analgesic and sedative
therapy that can be titrated to achieve goals of relieve of pain and suffering
without concerns for hemodynamic or respiratory consequences. Providers
should administer pain medications and other palliative therapies for the

5446
dying patient in the ICU, even if the possibility exists that such treatment
could possibly hasten death.161–163 A doctrine of “double effect” supports
adequate and aggressive palliation of pain to be differentiated from active
hastening of death and ethically justifiable, as long as the provider’s
primary intent is mitigating suffering.164–167
It is imperative that a patient in the ICU die with dignity and that an
individualized treatment plan be used at the end of life.161–163,166,167 This
involves use of preemptive medications aimed at treating pain, dyspnea,
anxiety, delirium, and any other symptoms that may be distressing to the
patient. It is important that ICU clinicians discuss with family members or
other individuals present what to expect during the dying process and
continue to provide support to the patient and their family.166 Some
practical recommendations for managing end-of-life issues in the ICU are
noted in Table 114.6.

TABLE 114.6 End-of-Life Care and Pain Management in the Dying

Intensive Care Unit Patient
Clarify and document the goals of care.
Notify interested individuals (surgeon, oncologist, specialty nurse, outpatient physician, or
nurse).
Emphasize to family that care continues but with new goals (i.e., care is not being
“withdrawn” but rather is focused on dignity and comfort).
Discontinue interventions and treatments that do not contribute to comfort (phlebotomy,
imaging, remove nonessential devices, silence alarms).
Provide sufficient analgesia, generally with systemic opioids (assure reliable intravenous
access, take into account recent and/or chronic opioid use, avoid arbitrary maximum analgesic
dosing, begin with a bolus of drug if planning to remove devices, including the endotracheal
tube, that raise the possibility of discomfort).
Educate and reassure family and staff that the purpose of opioids is to relieve and prevent
suffering, not to hasten death.
Consider removing the endotracheal tube because this can generally be done with no
discomfort as long as adequately premedicated.
Reassess regularly whether the goals of care (comfort) are being met and titrate pharmacologic
agents and interventions (clinically examine for signs of discomfort), determine whether vital
signs respond to interventions, and solicit family input: Do you feel your loved one is
comfortable?
Invite pastoral care, palliative care, or pain management specialists to participate, when
appropriate.
Consider transfer out of the intensive care unit, particularly to a palliative care unit, for
continued comfort care.

5447
Conclusions
Managing pain and providing effective analgesia are critical component of
comprehensive care of our ICU patients. Although the core principles of
pain management in general certainly apply in the ICU setting, the unique
issues related to complex acute and chronic medical illness, organ
dysfunction, communication difficulties, and integration with sedative
therapy and life support provide sound rationale for utilizing a
multiprofessional and patient-centered approach.

ACKNOWLEDGMENTS
The authors are grateful to Richard Mularski, MD, and Gregory Schmidt,
MD, who are coauthors of the chapter “Pain Management in the Intensive
Care Unit” published in the fourth edition of Bonica’s Management of
Pain in 2009. Their work paved the way for this updated chapter on pain
management in the ICU in the fifth edition of Bonica’s Management of
Pain.

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113. Leone M, Albanèse J, Viviand X, et al. The effects of remifentanil on endotracheal
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115. Bauer C, Kreuer S, Ketter R, et al. Remifentanil-propofol versus fentanyl-midazolam
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Care 2016;34:84–88.
121. Jones GM. Methadone in the critically ill—an unlikely player in intensive care medicine. J
Crit Care 2016;34:162.
122. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of
methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet
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123. Cicero TJ, Inciardi JA, Munoz A. Trends in abuse of OxyContin and other opioid analgesics
in the United States: 2002-2004. J Pain 2005;6(10):662–672.
124. Groudine SB, Fisher HA, Kaufman RP Jr, et al. Intravenous lidocaine speeds the return of
bowel function, decreases postoperative pain, and shortens hospital stay in patients
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125. Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59(2):263–268.
126. Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in
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128. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of
critically ill patients: a randomized trial. JAMA 2009;301(5):489–499.
129. Nishimori M, Ballantyne JC, Low JH. Epidural pain relief versus systemic opioid-based pain
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130. Block BM, Liu SS, Rowlingson AJ, et al. Efficacy of postoperative epidural analgesia: a
meta-analysis. JAMA 2003;290:2455–2463.
131. Bulger EM, Edwards T, Klotz P, et al. Epidural analgesia improves outcome after multiple rib
fractures. Surgery 2004;136(2):426–430.
132. Carrier FM, Turgeon AF, Nicole PC, et al. Effect of epidural analgesia in patients with
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139. Marik PE. Propofol: therapeutic indications and side-effects. Current Pharmaceutical Design
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prolongation of mechanical ventilation. Chest 1998;114(2):541–548.
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C H A P T E R 11 5
The Future of Pain Medicine: An
Epilogue
SCOTT M. FISHMAN and JAMES P. RATHMELL

The creation of this fifth edition of Bonica’s Management of Pain reflects

a major collaboration among many of the world’s leading authorities in the
basic and clinical sciences. As in prior editions, this text serves as a
resource for those who seek to increase their understanding of this aspect
of the human condition. However, it also provides an important reference
point—an elaboration on how far we have come and how far we have to
go in order to prevent, markedly reduce, and perhaps even cure the
pervasive problem of pain as a cause of unnecessary suffering, debility,
and economic hardship. As in the previous edition, we will again briefly
look ahead to where this journey may—and should—lead us before the
next edition of this textbook is written and reflect on what has happened
since the last edition was published in 2010.
The future is unpredictable; nonetheless, there are many current trends
that portend an optimistic course ahead. Foremost is the pivotal
recognition that pain is much more than a symptom and that its
consequences, in the acute or chronic form, may be devastating at every
level of human health. This profound understanding continues to transform
the perspective of modern medicine, offering greater possibilities for
dealing with the burden of disease than ever before. Soon after publication
of the prior edition of this text, the Institute of Medicine (now the National
Academy of Medicine) published its landmark report entitled “Relieving
Pain in America,” reporting that approximately 100 million Americans
suffer with chronic pain. It highlighted that clinicians remain substantially
undereducated about pain and ill prepared to respond.1 This education gap
has increasingly been seen as a one of the major root causes of the current
epidemic of prescription drug abuse, in that US clinicians were advised, if

5457
not forced, to recognize pain as a fifth vital sign with woefully inadequate
education, science, and clinical resources. Nonetheless, just as pain as the
fifth vital sign was a well-intentioned but poorly executed intervention
aimed at reversing decades of ignoring pain, the field of pain medicine
continues to progress along a notable course. Prior to the first edition of
this textbook, there were no pain specialists, pain journals, pain specialty
organizations, pain advocacy groups, pain training programs, or laws or
regulations specifically addressing the issues involved in delivering pain
relief. At the time that the third and most recent edition of this text was
written, the number of published reports in the realm of pain within the
medical literature was a fraction of those today and there was no pain
consortium at the National Institutes of Health (NIH). Clinical training of
pain specialists was in its infancy, with minimal guidance from accrediting
bodies. Certification of pain specialists through the American Board of
Medical Specialties (ABMS) was available only to anesthesiologists, and
the immense problem of pain management in primary care had barely been
raised.
Ironically, in part due to increased attention related to the opioid crisis
in the United States, recent unprecedented events suggest that we are on a
trajectory toward improved knowledge about pain and increased
commitment to pain relief, particularly care that is not solely focused on
opioids. These events include increasing demands for standards for pain-
related assessment and safe treatment in all health care facilities as well as
mandates for improving education in pain and its management. There is
little doubt that the future for pain management is inextricably linked to
both science and education. Core competencies for all health professionals
have now been established as a tool for educators to guide curriculum and
for accreditors to base evaluation of educational institutions. Today, pain
has growing representation in the NIH, and professional societies are
working diligently to further increase this new commitment. Subspecialty
clinical training has become much more integrative and multidisciplinary
as a result of groundbreaking revisions to requirements set by the
Accreditation Council of Graduate Medical Education (ACGME).
Previously, such requirements were predominantly directed by the
discipline of anesthesiology but have now been revised through an

5458
extraordinary collaboration of multiple disciplines. Subspecialty training
for a physician from any primary clinical discipline is now possible in
accredited programs that lead to certification as a pain specialist by the
ABMS. Similarly, the multidisciplinary field of palliative medicine is
designated as a subspecialty that is intertwined within many ABMS
primary specialties, a most recent example of medicine’s increasing
assimilation of symptom management and quality of life interventions.
Although pain medicine has also developed as a broad-based,
multidisciplinary subspecialty, its place in the overall structure of the field
of medicine as a whole is still in evolution. Reform initiatives are well
underway to refine the position of this emerging discipline in effort to
advance its research, education, and clinical missions. Great debate
remains over whether pain medicine should evolve into a more robust
subspecialty that integrates parts of many clinical disciplines or whether it
should become a primary specialty in its own right, but little progress has
been made toward changing the current training paradigm. How pain
medicine is ultimately positioned will greatly impact the field of
medicine’s ability to meet its fundamental obligations to mitigate
suffering.
At the time of publication of the prior edition in 2010, the National Pain
Care Policy Act of 2008 and 2009 ultimately became part of the US
Affordable Care Act in 2010. Since then, we have witnessed
unprecedented legislative and regulatory attention to pain and its
treatment. Recent developments suggest that states and the federal
government remain uncertain how to balance the needs of patients in pain
to have appropriate access to controlled substances with safety concerns
for the general public. Potential solutions have gained intense scrutiny by
the pain and law enforcement communities, respectively. Over time,
national policies by the U.S. Drug Enforcement Administration (DEA),
U.S. Food and Drug Administration (FDA), and the overarching
Departments of Justice and Health and Human Services will hopefully
evolve into rational approaches that balance compassion and safety.
Evidence suggests that the public health crises of prescription drug abuse
and inadequate pain management are receiving unprecedented attention
and action. The U.S. Department of Health and Human Services released a

5459
National Pain Strategy for addressing the clinical, education, and research
needs of current and future Americans in pain.2 Currently, the US
epidemic of prescription opioid abuse and excessive opioid prescribing has
led to a high pace of new legislative and regulatory attention. It remains
unclear if upcoming legislative and regulatory actions will simply restrict
opioid prescribing and access or improve the underlying educational
deficiencies that drive most excessive prescribing. The Obama
administration appeared to address the prescription drug abuse crisis as a
public health issue, whereas the Trump White House seems to see the
issue as more of a law enforcement problem. It remains to be seen if this
raised awareness and action will translate to improved access to safer and
more effective care for patients. Leading clinicians and scientists with
expertise in pain recently issued a special publication through the National
Academy of Medicine calling for clinicians to rationally counter the opioid
epidemic.3
The clinical practice of pain management, now more commonly termed
pain medicine, has changed dramatically since the creation of this textbook
in 1953. Under the direction of John Bonica, the establishment of
specialized centers that focus on pain management arose from
anesthesiology roots. These centers were initially based on an intensive
multidisciplinary model of care. Despite several decades of research firmly
establishing its effectiveness, such care is expensive and has been largely
unsustainable. Centers dedicated to this model have faced drastic
reorganization or become extinct.
These same anesthesiology roots of pain medicine also shaped another
important aspect of the field. With the influx of anesthesiologists came a
rise in the use of specific pain treatments that adopted regional anesthetic
or injection based techniques. Although any action taken to manage pain
should be considered an “intervention,” this new clinical arena based on
more invasive procedures, such as analgesic injections in the spine or
placement of implantable devices for pain, has been termed interventional
pain medicine. Currently, some experts contend that general pain medicine
and interventional pain medicine should be discrete disciplines with
practitioners separated based on interventional and noninterventional pain
practice. The heightened role of procedure-based pain practices, and some

5460
of the drive to isolate this part of care from the rest of pain medicine, has
almost certainly been driven by health care reimbursement systems, such
as those in the United States, that reward practitioners with higher payment
for procedural care than for almost all other aspects of pain care. Indeed,
the reimbursement for pain specialists who perform procedural
interventions is often many times that for those who treat the same group
of patients and spend the same amount or more time with them but do not
provide such interventions regardless of the level of evidence of predictive
outcomes that might reasonably justify one type of care over another. With
lucrative salaries in the private sector, too few of this new breed of
interventional pain physician have stayed in the academic realm and fewer
still have gone about conducting meaningful clinical trials to examine the
efficacy of their interventions.
Major health reform appeared imminent in the United States back in
2010, and that remains the case in 2018. Pain medicine, particularly
interventional pain medicine, stands at a crossroads as many of the
treatments that are part of currently accepted pain practice are expensive
but have little scientific evidence to support their efficacy. As the forces of
health care reform and evidence-based medicine unite to guide clinical
practice, many commonly used treatments are facing increased scrutiny by
payers. The unbridled growth of interventional pain medicine has already
moderated toward a more balanced form, where practitioners provide a
broad range of interventional and noninterventional treatment for common
pain conditions. Indeed, for economic, medical, social, and ethical reasons,
the field has moved toward a more uniform discipline, in which
individualized pain care is more similar than dissimilar based on a
relatively broad spectrum of mainstream treatment options, with
therapeutic choices based on weighing all available evidence and driven by
the best interests of each individual patient. Since publication of the fourth
edition, new clinical trials have appeared and numerous systematic reviews
and clinical practice guidelines have been published highlighting the lack
of evidence for sustained benefits from many interventions, such as spinal
procedures including epidural steroid injections and radiofrequency
ablation. This parallels heightened concerns about the lack of evidence for
long-term safety and efficacy of pharmacologic analgesia. Evidence for

5461
opioid use for chronic pain has been shown to be weak or inadequate
despite mounting evidence that risks are higher than previously believed,
and these risks increase markedly with dose. Taken together, as the field of
pain medicine evolves, its evidentiary foundation will be an increasingly
important factor in its credibility as a distinct discipline within medicine.
There is widespread agreement that existing systems are inadequate for
training clinicians to treat pain. Despite this, today’s clinicians are armed
with an unprecedented array of effective tools including pharmacologic,
behavioral, and physical therapies; invasive procedures; and cross-cultural
complementary and alternative treatments such as acupuncture and
meditation. Bringing these and new tools to bear on all cases of pain will
be a major challenge, requiring education for nonspecialist clinicians at the
professional school and postgraduate levels. Mandating substantive pain
education for all clinicians has been a missed opportunity that must be
corrected. It is to be seen whether or not the US National Pain Strategy
will lead to actions that address its pain management goals for improved
clinical care, foundational and far-reaching education, and substantially
increased research.
Pain will continue to be a pervasive problem for mankind, science will
continue its exponential growth in knowledge of pain and its treatment,
and society will increasingly recognize that pain management is integral to
the humane and economically viable practice of medicine. The current
medical, social, and economic crises in health care, if not medicine’s
covenant to mitigate suffering, demand nothing less than systemic
solutions to timely, integrated, and cost-effective pain relief. The current
controversies and opportunities in association with better understanding
and treatment of pain will likely push us toward a tipping point beyond
which the very structure of medicine is likely to have to change.
Currently, medicine possesses greater knowledge and more tools to treat
pain than ever before. Despite the inadequate treatment of pain,
undereducation of clinicians, and underfunding of research, medicine is
much further along today than it was even a decade ago—a trajectory that
bodes well for the future. The optimal organizational structure of science
and medicine for advancing understanding and treatment of pain is yet to
be defined. But it will most certainly require transcending current barriers

5462
that serve to fragment care, such as the illogical separation of the mind and
body within the whole person or the splintering of core elements of pain
management due to obsolete lines that separate one discipline from
another. Change will likely be proportionate to the value we place on
reducing suffering along with curing disease. Moreover, how general
clinicians and pain scientists of the future are supported and trained and
how the emerging discipline of pain medicine is positioned for continued
development and integration throughout health care will greatly impact
medicine’s ability to meet its mission to understand and treat pain.
Looking to the future, we appear to be headed for sweeping change in
health care that may well lead to new heights in medical research,
education, and clinical care for pain that is safer and more effective. This,
in the light of the remarkable progress that has already been made, is a
signal that medicine is rediscovering its fundamental ethos, most
assuredly, to cure when possible but to relieve suffering and provide
comfort always.

References
1. Institute of Medicine (US) Committee on Advancing Pain Research Care and Education.
Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and
Research. Washington, DC: National Academies Press; 2011.
2. National pain strategy: a comprehensive population health-level strategy for pain. Available
at: https://iprcc.nih.gov/sites/default/files/HHSNational_Pain_Strategy_508C.pdf. Accessed
May 15, 2018.
3. First, do no harm: marshalling clinician-leadership to counter the opioid-epidemic. Available
at: https://nam.edu/first-no-harm-nam-special-publication. Accessed May 15, 2018.

5463
 Index

Page numbers followed by b indicate boxes; those followed by f indicate

figures, and those followed by t indicate tables.

A
A1 cell group, 55, 55t
A5 cell group, 55, 55t, 56
A6 cell group, 55, 55t, 56f, 58–59
A6 nucleus, 56
A7 cell group, 55, 56–57, 827
AAAPT. See ACTTION-American Academy of Pain Medicine Pain
Taxonomy
AAPM. See American Academy of Pain Medicine
AAPT. See ACTTION-American Pain Society Pain Taxonomy
AAQ. See Acceptance and Action Questionnaire
ABA. See American Board of Anesthesiology
Abatacept, for rheumatoid arthritis, 492t, 493
ABC. See Addiction Behaviors Checklist
A-B-C model, in cognitive-behavioral therapy, 1406–1407
ABCDEF approach, 1789, 1789t
Abdominal aortic aneurysm, 569, 572, 1246
Abdominal cancer, visceral pain in, 755
Abdominal disease, chest wall pain in, 1201t
Abdominal pain, 1062–1078
acid suppressants for, 1071
acute, 1062

5464
adverse life events/stress and, 1067
antidepressants for, 1070
associated signs and symptoms in, 1064
biomarkers of, 1068
blocking afferent pathways in, 1070–1071
as chief complaint, 1062, 1062f
chronic, 1062
chronic, in children, 911, 923
clinical approach to, 1062–1064
complementary and integrative health in, 1072
conditions characterized by, 1062
contextual information on, 1063–1064
diagnostic testing in, 1064
genetic factors in, 1066–1067
history of, 1064
in HIV/AIDS, 986
lifestyle modifications for, 1068–1069
localization and character of, 1062–1063
medication- or drug-induced, 1064
microbial colonization in, 1067–1068, 1071
microbiome alteration for, 1071
neuromodulators for, 1069–1070
nonopioid analgesics for, 1069
opioid analgesics for, 1069
patient–provider relationship in, 1069
physical examination in, 1064
placebo response in, 1069
psychological factors in, 442, 1067, 1067f
psychological interventions for, 1070
quadratus lumborum block for, 883–885, 884f
sensitization and visceral hypersensitivity in, 1066, 1068
sensory afferents in, 1065, 1065f
sleep patterns in, 1068
smooth muscle relaxants for, 1071
somatic, 1062, 1066

5465
 spinal cord stimulation for, 1576, 1577f, 1578
susceptibility factors in, 1066–1068
time course of, 1063
treatment of, 1068–1072
triggering or alleviating factors in, 1063–1064
visceral, 1062, 1064–1066
Abdominal pain syndromes, in sickle cell disease, 966–968
Abdominal viscera, sympathetic and nociceptive nerve supply to, 116t
Abdominal wall pain, 613
Abducent nerve, 1162t
Abduction/external rotation (AER) test, 577
Aberrant behavior, 461, 1004–1005, 1517, 1517t
compliance monitoring for, 1012, 1013–1014
definition of, 1002t
separating motive from, 1004–1005
Aberrant Drug Behavior Index (ADBI), 465
Ablation. See also specific procedures
anatomy and physiology in, 1698, 1698f
bone metastasis, 729
brainstem, 1704–1705
for cancer-related bone pain, 748
for chronic pain, 1698–1707
efficacy of, 1698
image-guided tumor, 711t
intradiscal, 1646–1647
peripheral nerve, 1668
spinal, for cancer pain, 727–729
trigeminal nerve, 1692, 1694–1696
ABMS. See American Board of Medical Specialties
Abnormal illness behavior, 446
ABPMR. See American Board of Physical Medicine and Rehabilitation
ABPN. See American Board of Psychiatry and Neurology
Abscess(es)
epidural, 1635, 1761, 1762f
gluteal, 1208

5466
 lumbosacral plexopathy with, 1208
lung, 1194t
pelvic, 1208
psoas, 1208
Staphylococcus aureus and, 553
subphrenic, 1201t
Absorption (pharmacokinetics)
end-of-life organ dysfunction and, 1736
of intrathecal drugs, 1623
of local anesthetics, 1384, 1384f
of NSAIDs, 1317–1318
Absorption, in hypnosis, 1423, 1426
ABT-639, for cancer pain, 757
Abuse. See Sexual abuse, and pelvic pain; Substance abuse
Abuse-deterrent formulations (ADFs), 1346, 1349t
Acamprosate, 1513–1514
ACB. See Adductor canal block
ACC. See Anterior cingulate cortex
Acceptance, 12, 1405
Acceptance and Action Questionnaire (AAQ), 1418
Acceptance and commitment therapy (ACT)
for chronic pain, 1410
for children, 916, 918–919
group, 1439, 1456–1461, 1462t
for elderly patients, 935
for spinal cord injury, 593
Access to Controlled Medications Programme (ACMP), 220
Access to Opioid Medication in Europe (ATOME), 215
Accreditation Council for Graduate Medical Education (ACGME), 1752,
1752f, 1755–1756
ACE inhibitors, NSAID interaction with, 1325
ACEP. See American College of Emergency Physicians
Acetaminophen, 1316t, 1323
for abdominal pain, 1069
for acute pain, 830

5467
 in ambulatory surgical patients, 839
in war trauma, 838
for breast pain, 1190
for burn pain, 902, 903
for cancer pain, 682
for cancer pain in children, 793, 797–798
cardiovascular effects of, 1325
for children, 810–811, 812t, 916, 917, 922
for elderly patients, 931
in emergency department, 1775
for failed back surgery, 1294
for fibromyalgia, 538
for herpes zoster, 378, 379t
for hidradenitis suppurativa, 555
for HIV pain, 993, 994t
intravenous, 1323, 1324f
for low back pain, 1254, 1271
mechanism of action, 1315
for migraine, 991t, 1024, 1024t, 1133
for neuropathic pain, 1367
for osteoarthritis, 490
for pregnant patients, 1081
for prostate pain syndrome, 1104
rectal, 1323, 1324f
relative efficacy of, 829t, 1555t
for sickle cell disease pain, 963, 973
for spinal cord injury pain, 589
for tension-type headache, 1025, 1133
Acetazolamide, 1031
Acetic acid derivatives, 1316t, 1320–1321
Acetylcholine, 46t, 49
in autonomic nervous system, 118
in brainstem, 63
in emotion, 414
in integrated trigger point hypothesis, 507

5468
 in muscle physiology, 507–508
in nociceptive modulation, 55t
in spinal cord stimulation, 1571
in vigilance network, 70
Acetylcholinesterase (AChE), 507–508, 507f
Acetylcholinesterase inhibitors, intrathecal, 1628
Acetyl-L-carnitine, 337
ACGME. See Accreditation Council for Graduate Medical Education
Achalasia, noncardiac chest pain in, 1038, 1038f, 1195t
Achieving Balance in National Opioids Control Policy: Guidelines for
Assessment (WHO), 219
“Achieving Balance in State Pain Policy: A Progress Report Card,” 182
Acid perfusion test, in esophageal testing, 1047–1048
Acid–base balance, local anesthetics and, 1383
Acidosis, in cancer pain, 627
ACMP. See Access to Controlled Medications Programme
Acoustic neuroma, painful trigeminal neuropathy with, 1117
Acquired immune deficiency syndrome. See HIV/AIDS
ACR. See American College of Radiology; American College of
Rheumatology
Acromegaly, 489
Acromioclavicular joint, 1150–1156, 1155f
Acromioclavicular ligament, 1150, 1157f
ACS. See Acute chest syndrome; American Cancer Society
ACSM. See American College of Sports Medicine
ACT. See Acceptance and commitment therapy
ACTH. See Adrenocorticotropic hormone
Actin, 506–507, 507f
Action planning, 1476
Action potential, 26
compound muscle, 244–245
ectopic generation of, 1668
generation of, 26, 30–31
propagation of, 26, 31
sensory nerve, 244, 244f

5469
Action potential amplitude, 244
Action potential latency, 244
Action tendency, in anger, 1395
Activating transcription factor-3 (ATF-3), 745, 747
Active euthanasia, 168, 169
Active participant, patient as, 1709
Activities of daily living (ADLs), 303
cancer pain and, 664
occupational therapy for, 1498–1499
pain in elderly and, 929
Activity intolerance, 139
ACTTION-American Academy of Pain Medicine Pain Taxonomy
(AAAPT), 20, 22, 431
ACTTION-American Pain Society Pain Taxonomy (AAPT), 20, 21t, 22,
431
ACT-UP, 319, 319t
Acupressure
for cancer pain, 701
for childbirth pain, 946
Acupuncture, 145, 1549, 1553, 1555t
for abdominal pain, 1072
for cancer pain, 701–702
for cancer pain in children, 800
for childbirth pain, 946
for complex regional pain syndrome, 355
for dysmenorrhea, 1084
for elderly patients, 935
for fibromyalgia, 538
for herpes zoster, 379
for HIV pain, 997
for low back pain, 1254, 1272
NIH consensus conference on, 701–702
for prostate pain syndrome, 1104
for residual limb pain, 368
for sickle cell disease pain, 973

5470
 for spinal cord injury pain, 593–594
Acupuncture-like TENS, 1527
Acute, definition of, 1246
Acute brachial plexus neuritis, 1176
Acute chest syndrome (ACS), 956, 964–966
definition of, 964
diagnostic testing in, 965
embolism, infarction, and necrosis in, 964–966, 964f, 965f
management of, 965–966
radiographic findings in, 964, 964f
risk factors for, 964, 964t
Acute CPP crystal arthritis, 497
Acute inflammatory demyelinating polyradiculoneuropathy, 334
Acute motor axonal neuropathy, 333
Acute motor axonal sensory motor neuropathy, 333
Acute myeloid leukemia, 643
Acute pain, 826–849. See also specific anatomy and conditions
abdominal, 1062
ACTTION-AAPM taxonomy of, 20
acute and chronic effects of, 826
assessment of, 274
cancer-associated, 636, 636t
in children, 809–825
assessment of, 809–810
epidural analgesia for, 818–819
increased awareness and treatment of, 809, 809t
painful conditions in hospital care, 821–822
pharmacologic management of, 810–818
definition of, 11–12, 274
in emergency department, 1771
enhanced recovery programs for, 826, 837
gender or sex differences in, 841–843, 842t
inpatient pain services for, 843
intravenous lidocaine for, 1387
long-term impact of, 843

5471
nerve blocks for, 836–837, 1607
neurobiology of, 826–827
opioid analgesics for, 828–829, 832–833, 832t
in ambulatory surgical patients, 839
continuous epidural, 833–836, 833t
dose conversions of, 829, 829t
in elderly, 839
intra-articular, 837
intravenous, PCA, 832–833, 832t
in opioid-tolerant patients, 840–841
patient-controlled epidural, 835, 836t
pediatric, 812–817, 814t, 817t, 821–822
side effects in neuraxial administration, 834–835
single-dose neuraxial, 833, 833t
subarachnoid, 851–852
tramadol, 829
in war trauma, 838
in patients with substance use disorder, 462–464, 463t
perioperative, 826
postprocedural, 826
prevention of, 827–828
prognosis in, 17
regional analgesia for, 833–837, 850–896
block technique for, 850–851
combined spinal-epidural, 852
continuous epidural, 833–836, 850–851
contraindications to neuraxial techniques in, 853
dosage recommendations for, 833t
epidural medications for, 833–834
intra-articular, 837
local anesthetic–opioid combination in, 834
outcome studies of epidural analgesia, 835–836
patient-controlled epidural, 835, 836t
peripheral, 836–837
risks of epidural analgesia, 836

5472
 side effects of neuraxial drugs in, 834–836
single-dose neuraxial opioids in, 833, 833t
subarachnoid/intrathecal, 833, 851–852
in war trauma, 838
revolution in management of, 826
in sickle cell disease, 960t, 964–969
in special populations, 837–841
ambulatory surgical patients, 839
elderly, 839–840
obesity and obstructive sleep apnea, 841
opioid-tolerant patients, 840–841
war trauma, 838–839
systemic analgesia for, 828–833
α-adrenergic medications in, 831
antiepileptic drugs in, 830–831
excitatory amino acids in, 830
intravenous patient-controlled analgesia in, 832–833, 832t
nonselective noradrenergic and serotoninergic medications for, 831–
832
NSAIDs in, 829–830
opioid, 828–829
serotoninergic medications in, 831
steroids in, 831
transition to chronic pain, preventing, 1411–1412
treatment methods for, 828–837
Acute rehabilitation, 1493
Acute segmental modulatory effects, 52, 52f
Acyclovir, 377, 377t, 552–553, 738
Adalimumab, 492–493, 492t, 555
Adaptation
assessment of, 322–323
emotional, 411
Adaptation to the Intensive Care Environment (ATICE), 1784
Adaptive copers, 18
Adaptive designs, in clinical trials, 132

5473
ADBI. See Aberrant Drug Behavior Index
Addict, CSA definition of, 178
Addiction, 840, 1001–1002. See also Substance use disorder
basic science of disease, 1002–1003, 1003f
binary concept of pain and, 1003–1004
continuum approach to, 1004, 1004f
definition of, 12–13, 178, 1002t, 1772
diagnosis of, 1004
fear of, as barrier to use, 216
iatrogenic, 1002, 1002t
opioid, 1338, 1340–1341
pain treatment in patient with, 453–475
physical dependence v., 1001, 1002
terminology in state pain policies, 182, 183t
Addiction Behaviors Checklist (ABC), 465
Addiction specialist, referral to, 1728
Adductor canal block (ACB), 872–875
clinical effects of, 873
complications of, 874–875
indications for, 872–873, 873f
landmark approach for, 873
technique for, 873
ultrasound guidance for, 873, 874f
Adductor insertion avulsion syndrome, 1215
Aδ fibers, 26, 38, 41, 106, 107
in acute pain, 827, 831
in cancer pain, 647–648, 732–733
in complex regional pain syndrome, 343
in elderly, 839
in emotion, 414
in neuraxial analgesia, 853
in neuropathy, 330
in peripheral nerve stimulation, 1558–1559
in spinal cord stimulation, 1571, 1572f
Adenomyosis, 1087

5474
Adenosine, 46t, 1572, 1628
Adenosine antagonists, for noncardiac chest pain, 1053–1054
Adenosine triphosphate (ATP), 45, 46t, 48, 506–508, 627, 628
Adequate availability, of opioids, 206–207
Adequate stimulus, 5
ADH. See Antidiuretic hormone
Adhesions, pelvic, 1087–1088
Adiposis dolorosa (Dercum disease), 554, 1190, 1200t
Adjustment disorder, in cancer patients, 630
Adjuvant analgesics, 853–854
for acute pain, 834
bone pain, 686
for cancer pain, 685–687
for childbirth pain, epidural, 947t, 948
definition of, 685
for elderly patients, 933–934
general purpose, 685
for HIV pain, 994t
musculoskeletal, 685
neuropathic, 685–686
for priapism, 969
for sickle cell disease pain, 973
visceral, 686–687
Adjuvant chemotherapy, 778
ADLs. See Activities of daily living
Administrative proceedings, over pain management, 193–195
Adnexal pathology, pelvic pain in, 1080
Adnexal torsion, 1080
Adolescent and Pediatric Pain Tool (APPT), 791
Adolescent Sleep Habits Scale (ASHS), 915
Adolescent Sleep–Wake Scale (ASWS), 915
Adolescents
cancer pain in, 788–789
gender differences in pain, 92
Adrenal glands, 117t, 119t

5475
Adrenal pain syndrome, 756
Adrenergic receptors, 118
Adrenocorticotropic hormone (ACTH), 79, 419
ADS. See Anger Disorders Scale
Adson maneuver, 576–577, 1166
Adult Responses to Children’s Pain Questionnaire, 915
Advance care planning, 164–165
Advanced practice nurses, 1711
Adversarial relationship, 1725
Adverse Childhood Experience Questionnaire, 295
Adverse childhood experiences, 230, 295, 1293, 1302
Adverse Event Reporting System, 175
Adverse neural tension, 1481–1482, 1481f–1483f
Aerobic exercise, 1540–1543
AES. See Anger Expression Scale
Affect, pain, 79–80, 225. See also Emotion
measuring, 276–278, 290
primary and secondary features of, 417
Affective pathway, 65
Affective processing, in cancer pain, 628–629
Affective spectrum disorder, 527
Affective-motivational system, 65, 83
Afferent fibers and nerve, 5–6
in allodynia and neuropathic pain, 34b
targets of input, 39–43
visceral system, 103, 114, 753, 1065, 1065f
Affordability, of opioid analgesics, 218–219
Affordable Care Act, 1793
African Americans
money/power and, 145
pain and pain response in, 94–95, 139–140, 142
responses to pain treatment in, 95
sickle cell disease in, 955 (See also Sickle cell disease)
undertreatment of pain in, 95, 139–140
African Palliative Care Association, 220

5476
After pain, 236
Aftersensations, 397, 399
Age. See also Children; Elderly
and cancer pain, 600
and neck/arm pain, 1161
and pain, 140–141
and postherpetic neuralgia, 335
Agency for Health Care Policy and Research (AHCPR), 173, 826
Aggression, 1395–1396
Agoraphobia, 440, 442
Agreement with twist, 1475
AHA. See American Heart Association
AHCPR. See Agency for Health Care Policy and Research
AIDS. See HIV/AIDS
Alar ligaments, 1140–1141, 1142f
Albuterol, 1765
Alcohol injection
for neurolytic blockade, 711t, 716–717, 716f, 1653, 1654
for trigeminal neuralgia, 1115
Alcohol neuropathy, 332
Alcohol use, 297. See also Substance use disorder
and fibromyalgia, 530
and gout, 498
laboratory tests for, 1509
pharmacotherapy for, 1513–1514
quantities in, 1508, 1509t
Alcohol Use Disorders Identification Test (AUDIT), 231, 297, 1006, 1509
Alcohol Use Disorders Identification Test Consumption Questions
(AUDIT-C), 297
Alcoholics Anonymous, 1511, 1513
Alertness, 70
Alexander technique, 1551
Alfentanil, 592, 832t, 833t, 902, 903
Alkalinization, of local anesthetics, 1386–1387
“All or nothing,” in action potential, 26

5477
Allergies
fibromyalgia and, 534
identifying, 232, 239
to local anesthetics, 1388–1389, 1596
to morphine, 1344
to NSAIDs, 1326–1327
Alleviation, 1434
Allied spectrum conditions, 525
Allodynia, 13, 58, 71
afferent contributions to, 34b
central pain and, 396, 398
complex regional pain syndrome and, 343, 1529–1530
definition of, 58
desensitization for, 1529–1530
dorsal horn and, 107
dynamic mechanical, 34b
male pelvic pain and, 1102
neck pain and, 1163
nerve pain and, 1669
neuropathy and, 330
opioid-induced hyperalgesia and, 690–691, 1626
postherpetic neuralgia and, 380–381, 383, 1186
prefrontal cortex in, 70
sensory testing for, 235–236
spinal cord injury and, 585
spinal cord stimulation and, 1571, 1572
Allopurinol, 500, 556, 1224
Allostasis, 419
Allostatic load, 419
Almotriptan, 1024t
intrathecal, 1626–1627
α-Adrenergic medications, for acute pain, 831
α-Adrenergic receptors, 118
α2 Macroglobulin, 1650
α2-Adrenergic agonists

5478
 for bone pain in cancer, 747
intrathecal, 1626–1627
α2δ ligands
for neuropathic pain, 1374
for painful neuropathies, 336–337
Alprazolam, for noncardiac chest pain, 1054
Alteration, 1434
Alternative medicine, 145, 1547, 1547t. See also Complementary and
integrative health
Alternative study designs, 131
Alvimopan, 683, 817, 1341
Alzheimer disease, pain processing in, 930
Amantadine, 353
Ambulatory infusion pumps, 701
Ambulatory surgical patients, acute pain management in, 839
American Academy of Hospice and Palliative Medicine, 1739
American Academy of Neurology, Quality Standards Subcommittee of,
1113
American Academy of Pain Medicine (AAPM), 16, 20, 157, 1517
American Academy of Pediatrics, 802, 952
American Association of Orofacial Pain, 1132, 1132t
American Board of Anesthesiology (ABA), 9, 1751–1752
American Board of Medical Specialties (ABMS), 1751–1752, 1793
American Board of Physical Medicine and Rehabilitation (ABPMR), 9,
1752
American Board of Psychiatry and Neurology (ABPN), 9, 1752
American Cancer Society (ACS), 173
American College of Emergency Physicians (ACEP), 1770, 1778
American College of Physicians (ACP), on manipulation, 1550
American College of Radiology (ACR), Appropriateness Criteria, 251
American College of Rheumatology (ACR), 21–22, 490, 526, 627, 1356
American College of Sports Medicine (ACSM), 1540–1541
American Geriatrics Society, 931–932
American Heart Association (AHA), 1314, 1540–1541
American Holistic Nurses Association, 1555

5479
American Medical Association, 311, 1421, 1546
American Pain Society (APS)
on cancer pain relief, 173
on chronic pain in children, 913
on manipulation, 1550
on opioid therapy, 1517, 1724
pain taxonomy of, 20
standards for pain centers, 1494
in United States v Hurwitz, 200
American Physical Therapy Association, 1522
American Psychiatric Association
Diagnostic and Statistical Manual of Mental Disorders (DSM), 430–
432, 432f, 432t
on panic disorder, 442
on substance use disorder/substance abuse, 178, 1508, 1773
American Psychological Association, 1421
American Society of Addiction Medicine, 178, 1511
American Society of Anesthesiologists
acute pain management standards, 826
Closed Claims Project, 1758, 1758t, 1759f
continuum of depth of sedation, 900, 900t
Task Force on Perioperative Management of Patients with Obstructive
Sleep Apnea, 841
American Society of Clinical Hypnosis (ASCH), 1421, 1431–1432
American Society of Clinical Oncology (ASCO), 160, 763, 779, 782
American Society of Regional Anesthesia and Pain Medicine (ASRA),
836, 870, 887
Amines, biogenic. See also Norepinephrine; Serotonin
in depression–pain association, 436
Amino acids
excitatory, 45–47, 830
inhibitory, 48
Amino amides, 1382, 1386t
Amino esters, 1382, 1386t
Amitriptyline

5480
 for central pain, 400, 401t
for children, 916
for chronic pelvic pain, female, 1086
for elderly patients, 933
for erythromelalgia, 559
for fibromyalgia, 535, 536t,
for HIV pain, 994t
for male pelvic pain, 1105
for migraine, 990t
for migraine prevention, 1023t
for neuropathic pain, 400, 1359–1361, 1360t, 1361t
for noncardiac chest pain, 1053
for painful neuropathies, 336
for phantom pain, 365, 795
for postherpetic neuralgia, 384t, 386
for postherpetic neuralgia prevention, 390
for sensory mononeuropathies, 559
for spinal cord injury pain, 591
for tension-type headache, 1025, 1133
topical, as adjuvant analgesic, 685
for vulvodynia, 1092
Amlodipine, for abdominal pain (IBS), 1071
AMPA receptor(s), 45, 46t, 733, 827, 1100
AMPA receptor antagonists, for cancer pain, 757–758
Amphetamines, urine testing for, 1509t
Amphiarthrodial joints, 484
Amphotericin B lozenges, 738
Amplification, 913
Amplified reflection, for behavioral change, 1475
Amplitude, in nerve conduction studies, 244
Amputation
pain associated with, 571
phantom pain in (See Phantom limb pain)
residual limb pain in, 363, 368
stump pain in, peripheral neurectomy for, 1670

5481
AMSTAR. See Assessment of Multiple Systematic Reviews
AMT. See Anxiety/anger management training
Amygdala, 62, 65, 70, 108
in addiction, 1002–1003, 1003f
in defensive behavioral system, 70
in depression–pain association, 436, 436f
in emotion, 412, 412f
lesions of (Klüver-Bucy syndrome), 70
in migraine-related pain, 70
in nociceptive modulation, 55, 55t, 57
nuclei and subregions of, 70
in pain–ANS interaction, 114
projection pathways to, 45
in stress, 419
in stress-induced analgesia and hyperalgesia, 59
Amyloid neuropathy, 333
Anakinra, 497, 500
Analgesia
definition of, 13
opioid-produced, 1336–1337
preventive, 827–828
stimulus-induced, 64
stress-induced, 59
Analgesic(s). See also specific types and agents
definition of, 1333
WHO ladder of, 205, 378
in cancer pain, 676, 677, 679–681, 680f, 711, 738
in HIV pain, 205, 993, 993f
in sickle cell disease pain, 973, 973t
Analgesic, Anesthetic, and Addiction Clinical Trial Translations,
Innovations, Opportunities, and Networks (ACTTION), 20, 21t, 22,
431
Analgesic balms, topical, 1356–1357, 1356t
Analgosedation, in ICU, 1782, 1788–1789
Anaphylactoid reactions, 1765

5482
Anaphylaxis, 1764–1765
Anastrazole, for endometriosis, 1087
Anatomy. See specific anatomic structures
Anatomy-based classification, 15
Ancient view of pain, 1, 1t
Anderson-Fabry disease. See Fabry’s disease
André, Nicolas, 1109
Androgen deficiency, opioid-induced, 1338
Anembryonic pregnancy, 1082t
Anesthesia dolorosa, 13, 1123, 1129
Anesthesiology, history of, 1751
Anesthetic model, of cancer pain, 616, 616f
Aneurysms
abdominal aorta, 569, 572, 1246
back pain with, 1246–1247, 1251
gastroduodenal artery, 1246
imaging of, 251, 252f, 255, 256, 257f
lumbosacral plexopathy with, 1208
management of, 572, 572f
neck pain with, 1233
thoracic aorta, 572, 1193t–1194t
Anger, 80, 81–82, 1301, 1392–1404
arousal in, 82
behavioral therapy for, 1401
cognitive-behavioral therapy for, 1401
cultural background of, 1392
current research in, 1393–1398
denial of, 81
measurement of, 1398–1399, 1398t
opioid deficit hypothesis of, 1397–1398
pain amplification in, 81
physiologic mechanisms in, 1394–1395
psychoanalytic background of, 1392–1393
psychological constructs in, 1395, 1395t
psychotherapeutic management of, 1399–1401

5483
 target specificity in, 81
Anger Disorders Scale (ADS), 1398t, 1399
Anger Expression Scale (AES), 1398
Anger management style, 1395–1398
Anger-in, 1396–1397
Anger-out, 1396, 1397–1398
Angina pectoris, 1191, 1193t
atypical, 1041–1042
chronic refractory, 1191
diagnosis of, 1041–1042
linked, with noncardiac chest pain, 1038
spinal cord stimulation for, 1191, 1575–1576, 1577f
typical, 1041–1042
Angiokeratoma, 559
Angiokeratoma corporis diffusum, 559–560
Angioleiomyoma, 560, 561t
Angiolipoma, 560, 561t
Angiotensin receptor blocker, for migraine, 990t
Angiotensin-converting enzyme (ACE) inhibitors, NSAID interaction
with, 1325
Anhedonia, 433
Anise, for abdominal pain, 1072
Ankle block, 882–883
clinical effects of, 883
complications of, 883
indications for, 882
landmark technique for, 882
ultrasound guidance for, 882–883, 883f
Ankle/arm indices, 568, 568f
Ankylosing spondylitis, 484, 493–495
cauda equina syndrome with, 495
chest wall pain with, 1187–1188, 1198t
fibromyalgia with, 527
laboratory findings in, 494
low back pain in, 1247

5484
 pathophysiology of, 493–494
radiography of, 494, 494f, 1188
signs and symptoms of, 494, 494f
treatment of, 494–495, 1188
Annulus fibrosis, 1138–1139
Anorectal pain, in HIV/AIDS, 986–987
Anorexia/cachexia/asthenia, in cancer, 617
ANS. See Autonomic nervous system
Antenatal childbirth education, 945
Anterior cingulate cortex (ACC), 66f, 67–68, 114
deep brain stimulation of, 1587–1589
in depression–pain association, 436, 436f
in emotion and pain, 412, 417
functional imaging of, 67
in nociceptive modulation, 55t, 56f, 57
opioid analgesics and, 1336–1337
in pain processing, 67–68, 68f
in pain–ANS interaction, 114
Anterior cingulotomy, 1701–1703, 1702f, 1702t
Anterior corticospinal tract, 40f
Anterior cutaneous nerve, 1146
Anterior interosseous syndrome, 267, 1675
Anterior longitudinal ligament, 1141, 1142f
Anterior lumbar interbody fusion, 1284, 1284t
Anterior reticulospinal tract, 40f
Anterior spinocerebellar tract, 40f
Anterior spinothalamic tract, 40f
Anterolateral fasciculus, 40f
Anterolateral pathways, of axonal projections
spinoreticular and spinomesencephalic, 44
spinothalamic, 43
Anthropologic theories, of depression, 438
Antibiotics
for acute chest syndrome, 965
for cancer complications, 679

5485
 for cellulitis, 553
for epidermal cyst, 555–556
for furunculosis and carbuncle, 553
for hidradenitis suppurativa, 555
for infectious arthritis, 501
intradiscal, 1649
for pelvic inflammatory disease, 1080
for prostate pain syndrome, 1103–1104
for reactive arthritis, 496
Anticholinergic agents
for abdominal pain, 1071
for oral mucositis prevention, 738
for prostate pain syndrome, 1104
Anticipation of pain, 436
Anticoagulation. See also specific anticoagulants
precautions in nerve blocks, 887
precautions in neuraxial analgesia, 853, 870
as relative contraindication to nerve block, 1596
risks of epidural analgesia with, 836, 1758, 1759
for thoracic outlet syndrome, 579
Anticonvulsants. See Antiepileptic drugs
Antidepressants
for abdominal pain, 1070
for anxiety, 441
for burn pain, 902
for cancer pain, 687
for central pain, 400–402, 401t, 402f
for chemotherapy-induced peripheral neuropathy, 686
for children with chronic pain, 916, 917–918
for complex regional pain syndrome, 352
for depression, 436, 438–439, 1416–1417
for elderly patients, 933
for erythromelalgia, 559
for HIV pain, 994t, 995–996
for low back pain, 1271

5486
 for male pelvic pain, 1105
functional effects of, 1103t
for migraine, 990t
for neuropathic pain, 400–402, 686t, 1359–1362, 1360t, 1361t
for noncardiac chest pain, 1052–1053, 1052t
for painful neuropathies, 336, 337
for phantom pain, 365
for postherpetic neuralgia, 384t, 386, 1118, 1186
for sickle cell disease pain, caution with, 973
for spinal cord injury pain, 591
and suicide risk, 468
tricyclic (See Tricyclic antidepressant(s))
Antidiuretic hormone (ADH), opioid analgesics and, 1338
Antidromic SNCS, 244, 244f, 245f
Antiemetics
for cancer patients, 683–684, 684t, 687
for migraine, 991t, 1024, 1024t
for opioid-induced nausea, 1337, 1339
Antiepileptic drugs
for abdominal pain, 1069–1070
for acute pain, 830–831
for anesthesia dolorosa, 1123
for burn pain, 902
for central pain, 400–403, 401t, 402f
for chemotherapy-induced peripheral neuropathy, 686
for children
in acute pain, 812, 812t
in chronic pain, 916, 917–918
for complex regional pain syndrome, 352
for elderly patients, 933
for failed back surgery, 1295
for fibromyalgia, 530, 537, 537t
for HIV pain, 994t, 996
in intensive care unit, 1787
for male pelvic pain, 1105

5487
 functional effects of, 1103t
for migraine, 990t, 1133
for migraine prevention, 1023t
for neuropathic pain, 1362–1366, 1363t–1365t
for painful neuropathies, 336–337
for phantom pain, 365
for postherpetic neuralgia, 383–386, 384t, 1118, 1186
for postherpetic neuralgia prevention, 390
for spinal cord injury pain, 590–591
and suicide risk, 468
for trigeminal neuralgia, 1113–1115, 1691, 1692
for vagal neuralgia, 1122
Antihistamine(s)
for anaphylaxis, 1765
for opioid-induced pruritus, 1341
for priapism, 969
Antihistamine muscle relaxant, 1352t, 1354
Antihypertensive agents, NSAID interaction with, 1325
Antineutrophilic cytoplasmic antibodies-associated vasculitides, 547
Antioxidants, 352, 1072
Antiphospholipid syndrome, 548
Antipsychotics
for anxiety, 441
for burn pain, 902
for cancer pain, 687
Antiretroviral therapy. See also HIV/AIDS
headache with, 989–992
interactions with analgesics, 995
neuropathy in, 331, 987–989
pain and side effects with, 985–1000
Antispasmodic medications, 685, 1052, 1071
Antispasticity medications, 589, 685
Anti-TNF agents. See Tumor necrosis factor (TNF) inhibitors
Antitussive effects, of opioid analgesics, 1338
Antiviral therapy

5488
 for herpes simplex, 552–553
for herpes zoster, 377–378, 377t, 391, 1118, 1186
Anxiety, 79–80
in abdominal pain, 1067, 1068
assessment for, 227, 229–230, 237, 296, 298, 322
behavioral approach for, 1416
in chest wall pain, 1191, 1201t
in chronic pain, 440–442, 1414–1420
in children, 912, 913, 914–915
impact on functioning, 1414–1415
interaction of anxiety, depression, and chronic pain, 1415
prevalence of, 1414
cognitive-behavioral therapy for, 441, 1417–1418
in complex regional pain syndrome, 348–349
in difficult patients, 476–477
in failed back syndrome, 1292–1293, 1295
in female pelvic pain, 1084–1085
in fibromyalgia, 80, 440
in low back pain, 1251
in noncardiac chest pain, 1034, 1041, 1050, 1055
pharmacotherapy for, 441, 1417
primary care and, 1725
in spine surgery candidates, 1304
Anxiety disorders, 440–442
in cancer patients, 630
DSM criteria for, 441, 441t
Anxiety sensitivity, 77, 79–80
Anxiety/anger management training (AMT), 1401
Anxiolytics, 352, 441, 687, 902
Aorta
pain management for, 572, 572f
sympathetic and nociceptive nerve supply to, 115t–116t
thoracic, diseases of, 1193t–1194t
Aortic aneurysm
abdominal, 569, 572, 1246

5489
 low back pain with, 1246, 1251
lumbosacral plexopathy with, 1208
management of, 572, 572f
rupture of, 569, 572
thoracic, 572, 1193t–1194t
Aortic dissection, 569, 572
Aortic pain, 569
Aortic regurgitation, 1193t
Aortic stenosis, 1193t
Aorticorenal ganglion, 113f
Aortocaval compression, in pregnancy, 943–944, 944f
Apgar, Virginia, 940
Apgar score, 940
Apical ligaments, 1141, 1142f
Apophyseal facet syndrome, 1198t
Appendix, sympathetic and nociceptive nerve supply to, 116t
Appraisal, 77–78, 84–85
APPT. See Adolescent and Pediatric Pain Tool
Aprepitant, 684, 684t, 1072
APS. See American Pain Society
Aquatic therapist, 1712
Arachidonic acid, 1315
Arachnoid, of spinal cord, 39
ARAS. See Ascending reticular activating system
Aretaeus, 1109
Aristotle, 1, 1392
Arizona, addiction-related terminology in, 183t
Arm
anatomy of, 1138–1158
biomechanics of, 1138
movement of, 1156, 1157f, 1158, 1158f, 1159f
peripheral nerve supply of, 1151f
segmental nerve supply of, 1150f
sympathetic contributions to, 117t, 1148–1150, 1155f
Arm pain, 1138–1179

5490
age and psychosocial history in, 1161
anatomy in, 1138–1158
brachial plexus, 1146–1150, 1147f, 1148f, 1148t
cervical nerves, 1143–1146, 1145f, 1146f
cervical plexus, 1146, 1146f, 1147f
cervical spine, 1138–1141, 1139f, 1144f
dermatomes, 1145, 1147f
neck musculature, 1141, 1143f
pectoral girdle and shoulder, 1150–1158, 1155f, 1156f, 1157f
vertebral arteries, 1142–1143, 1145f
vertebral canal, 1142, 1144f
associated symptoms in, 1160–1161
common causes of, 1138, 1168–1177
differential diagnosis of, 1150, 1159
electrodiagnostic studies in, 1168
epidemiology of, 1158–1159
family history in, 1161
general observations in, 1162
history of, 1159–1161
laboratory examination in, 1166–1168
location/radiation of, 1160
mechanical, 1138, 1160
modifying factors and drug history in, 1160
myofascial, 1160
in neck and arm pain, 1161
neuropathic, 1160
nonmechanical, 1160
onset of, 1159, 1160
past medical history and systems review in, 1161
patient evaluation in, 1159–1168
physical examination in, 1162, 1166
quality of, 1160
radiographic studies in, 1168–1169
referred, 1160
skeletal, 1160

5491
 special tests in, 1165–1166
surgical history in, 1161
Aromatase inhibitors
for adenomyosis, 1087
for breast cancer, 622–623, 782
for endometriosis, 1087
Aromatherapy, for elderly patients, 935
Around-the-clock regimens, for cancer pain, 678, 681, 689–690
Arousal
anger and, 82
autonomic, and subjective experience, 413
in emotion, 411
in pain processing, 70–71
reticular formation and, 63
Art therapy, 800–801
Arterial dissection, imaging of, 251, 255f
Arterial spin labeling (ASL), 62–63
Arterial thoracic outlet syndrome, 267, 576, 1176. See also Thoracic outlet
syndrome
Arterial (ischemic) ulcers, 550, 569–570
Arteriovenous malformation (AVM), 251, 253f, 255
Arteritis, giant cell, 502, 1031
Artery(ies). See also specific arteries
claudication of, 567–569, 567f
disorders of, pain associated with, 567–570
innervation of, 566
pain management for, 572, 572f
Arthritis, 484–503. See also Osteoarthritis; Rheumatoid arthritis
adjuvant analgesics for, 685
anatomy in, 484–485, 484f
autoimmune, 987
basic considerations in, 484–485
in children, 909–910
clinical considerations in, 487–502
costovertebral, 1188, 1198t

5492
 crystal, 484, 497–500
epidemiology of, 484
fibromyalgia with, 527, 532
gouty, 498–499
group therapy for
acceptance-based, 1462t
cognitive-behavioral, 1442, 1443t, 1447t, 1448t, 1453t
mindfulness-based, 1457t
heat therapy for, 1523
in HIV/AIDS, 987
IBD-associated, 496–497
impact and burden of, 484
infectious, 500–501
laser therapy for, 1524–1525
low back pain in, 1247
manubriosternal, 1189–1190
neck pain with, 1233
number of joints affected in, 485–486, 486t
pattern recognition in, 486
physical examination in, 486
psoriatic, 484, 496, 496f
reactive, 484, 495–496, 987, 1247
septic, 493, 500–501, 987
shoulder and pectoral girdle, 1150, 1155f
sternoclavicular joint, 1189, 1199t
synovial fluid examination in, 486–487, 486t, 489, 491, 494, 496
systemic features of, 486
Arthritis, Diet, and Activity Promotion Trial, 489
Arthritis Impact Measurement Scale, 129
Arthritis mutilans, 496
Arthropathy, in HIV/AIDS, 987
Articular cartilage, 485
Articular nerves, 485
Ascending pathway, multisynaptic, 43
Ascending reticular activating system (ARAS), 63

5493
Ascending tracts, 39, 40f, 43–45
ASCH. See American Society of Clinical Hypnosis
ASCO. See American Society of Clinical Oncology
Ashcroft, John, 202
ASHS. See Adolescent Sleep Habits Scale
ASL. See Arterial spin labeling
Aspartate, 45, 46t, 1353
ASPEN syndrome, 969
Aspirin, 1316t, 1320
for acute pain, 829–830
for cancer pain, 681
for children, 810
for erythromelalgia, 559
gastrointestinal toxicity of, 1327
hematologic effects of, 1327
history of, 1315
for livedoid vasculitis, 548
for migraine, 1024, 1024t, 1133
relative efficacy of, 829t, 830
renal toxicity of, 1327–1328
for tension-type headache, 1025
ASRA. See American Society of Regional Anesthesia and Pain Medicine
Assessment of Multiple Systematic Reviews (AMSTAR), 133
Assessment of pain. See Measurement of pain; Pain evaluation
Assisted conception, complications of, 1082–1083
Associative tolerance, 1339
Asthenia, in cancer, 617
ASWS. See Adolescent Sleep–Wake Scale
Asymbolia, pain, 108
Atenolol, for migraine, 990t
ATF-3. See Activating transcription factor-3
Atheroembolism, 569
Atherosclerosis, intermittent claudication in, 567–569, 567f
ATICE. See Adaptation to the Intensive Care Environment
Atlantoaxial joint, 1138, 1140, 1141

5494
Atlantoaxial joint block, 1171, 1237, 1237f, 1239, 1605–1606, 1606f
Atlantoaxial unit, 1141
Atlantooccipital joint, 1138, 1140–1141
Atlantooccipital joint block, 1237, 1237f, 1239
Atlantooccipital unit, 1140–1141
Atlas (C1 vertebra), 1138, 1140f
At-level spinal cord pain, 585–587, 585f, 586f, 587f
ATOME. See Access to Opioid Medication in Europe
ATP. See Adenosine triphosphate
Attention
anxiety and, 80
components of, 70
executive, 71
fibromyalgia and, 533–534
functional imaging of, 71, 71f
in pain processing, 70–71, 71f
selective or focused, 70
supervisory function of, 70–71
sustained, 70
in vigilance network, 70
Attrition, in clinical trials, 128
Atypical angina, 1041–1042
Atypical facial pain, 1129
AUDIT. See Alcohol Use Disorders Identification Test
Auerbach’s (myenteric) plexus, 118, 120f
Aura, in migraine, 1133
Australia
Aboriginal people in, 142, 146
pain medicine in, 1754, 1755
Austria, pain medicine in, 1755
Autogenic training, 1426
Autoimmune arthritis, 987
Autoimmune demyelinating neuropathies, 333–334
Automaticity, 1423
Autonomic centers

5495
 in CNS, 114–118
in spinal cord, 118, 118t
Autonomic dysreflexia, spinal cord injury and, 582, 584
Autonomic nervous system, 110–119, 110f
activation, in pain, 225
arousal in, and subjective experience, 413
distribution to body structures, 113f
in emotion, 412–414
feedback in, 413
ganglia of, 110–114, 110f, 111f
in myofascial pain (trigger points), 511–512
nerve supply to body structures, 111t, 115t–117t
in noncardiac chest pain, 1041
parasympathetic division of, 110, 110f, 111, 111t, 112f, 113f
physiology of, 118, 119t
sympathetic division of, 110, 110f, 111–114, 112f, 113f
transmission in, 118
Autonomic responses, 79
Autonomy, 166
Availability, of opioids, 206–207, 215, 216t, 220–221. See also Barriers,
to pain relief
Avascular necrosis (AVN)
in cancer, 748
core decompression for, 970, 970f
Ficat and Steinberg staging of, 970, 970t
“fish mouth” or step-like depression in, 969–970, 970f
hip, 969–971, 970f, 970t
in sickle cell disease, 969–971, 970f
treatment of, 970–971
Aversive classical conditioning, 427
Aversiveness, in pain, 141
Avicenna, 2–3, 3f, 7
AVM. See Arteriovenous malformation
AVN. See Avascular necrosis
Avoidance

5496
 in classical conditioning, 427–428
as coping style, 903–904, 904f
in pain management, 1434
Awareness techniques, 1434
Axes, of pain, 18–20, 19t, 20t
Axial neck pain, 1138
Axial spine pain
dorsal rhizotomy or ganglionectomy for, 1682
peripheral nerve stimulation for, 1564
peripheral neurectomy for, 1671
Axillary block, 861–862
clinical effects of, 862
indications for, 861
landmarks for, 861
nerve stimulation for, 861
suprascapular block with, 862–863
techniques for, 861
transarterial, 861
ultrasound guidance for, 861, 862, 862f, 864f
Axillary nerve, 1148f, 1151f, 1153t
Axis (C2 vertebra), 1138, 1140f
Axonal neuropathy, 330
Axonal projections
spinoreticular and spinomesencephalic tract, 44–45
spinothalamic tract, 43–44
targets of, 43–45
Ayurvedic medicine, 1554
Azathioprine
for ANCA vasculitis, 547
for bullous pemphigoid, 558
for epidermolysis bullosa, 558
for IBD-associated arthritis, 497
for leukocytoclastic vasculitis, 546
for pemphigus vulgaris, 557
for polyarteritis nodosa, 547

5497
 for reactive arthritis, 495

B
Bacillus Calmette-Guérin (BCG) intravesical therapy, 755–756
Back pain. See also Low back pain
alternative medicine for, 145–146
axial
dorsal rhizotomy or ganglionectomy for, 1682
peripheral nerve stimulation for, 1564
peripheral neurectomy for, 1671
in cancer, 613
in childbirth, 945–946, 945f
in children, 910, 922
culture and, 142
depression and, 80–81
epidemiology of, 1717
gender differences in, 91
genetics and, 96
group therapy for
behavioral v. exercise and physical therapy, 1456
cognitive-behavioral, 1442, 1443t, 1445t, 1446t, 1449t–1452t, 1454t,
1461
individual treatment v., 1439–1442, 1440t–1441t
mindfulness-based, 1457t, 1459t, 1460t
healthcare costs of, 1717
malpractice claims over, 1759f
in pancreatic cancer, 639
patient improvement in ineffective treatment, 124, 124f, 124t
plasticity in, 72, 72f
spinal cord injury and, 583–584
spine clinics for, 1717–1721
Back Pain Functional Scale, 1305
Back school, 1272
Background pain, in burn injury, 903
Baclofen, 1352t, 1355
as adjuvant analgesic, 685

5498
 for central pain, 402–403
for complex regional pain syndrome, 354
intrathecal, 714t, 715, 1624, 1625t, 1627, 1631t, 1639
complications of, 1764
for neuropathic pain, 1375
for spinal cord injury, 590
mechanism of action, 1354
for spinal cord injury, 589–590
with spinal cord stimulation, 1572
for trigeminal neuralgia, 1114–1115
Baclofen withdrawal, 1639, 1764
Bacterial arthritis, nongonococcal, 500–501
Bad pain (maldynia), 16
Balance
in drug policy, 174, 181, 184, 187–188, 207, 207t, 1001
in emergency department, 1774
Balloon compression, for trigeminal neuralgia, 1695
Balloon distention protocol, in noncardiac chest pain, 1039–1040, 1039f,
1040f, 1046–1050
Balms, topical analgesic, 1356–1357, 1356t
Bamboo spine, 493, 1188
Barbiturates
for palliative sedation, 1739
urine testing for, 1509t
Bariatric surgery, neuromuscular manifestations after, 332
Barium esophagram, for noncardiac chest pain, 1042
Barriers, to pain relief, 153–156
addressing, 220–221, 1725–1726
in cancer, 623–625
distribution system, 217–218, 218f
economic, 218–219
identifying, 153–155
opioid, 172–173, 215–221, 216t
patient, 155
pediatric, 789–790, 923

5499
 primary care and, 1724–1726
professional, 153–154, 215–216
in cancer, 623–625
deficiencies in physician education, 153–154, 216, 623–625, 1793
fear of scrutiny or liability, 154, 216, 676, 1725–1726
“patient dumping,” 154
primary care and, 1724–1726
regulatory, 154, 216–217, 217t, 1725–1726
societal, 155
Basal ganglia, 62, 108
Baseline observation carried forward, 128
Baseline similarity, of study groups, 127
Baszanger, Isabelle, 9
Battered nerve, 1292
Bausch, Johannes, 1109
Bayer Institute for Health Care Communication, 480
Bayesian statistical inference, 132
BCG. See Bacillus Calmette-Guérin (BCG) intravesical therapy
BDI. See Beck Depression Inventory
BDNF. See Brain-derived neurotrophic factor
Beat frequency, 1528
Beatty’s maneuver, 1217
Beaumont, William, 1071
Beck, Aaron, 1405, 1408
Beck Depression Inventory (BDI)
in cancer patients, 630, 631t
in chronic pain, 320, 322
in noncardiac chest pain, 1053
in screening for spine surgery/implantation, 1300, 1304
in substance use disorder, 467
Bee venom, 516
Beecher, Henry, 7, 1405
Beers Criteria, 931–932
Before-after study, 123–124
Behavior

5500
 and emotion, 411
and illness, 80, 445–446, 447–448, 448t
in pain, 14, 82–83
in anxiety and depression, 1416
assessment of, 313–314
culture and, 141–143
in Loeser’s model of pain, 85
observing and quantifying, 321–322
variables underlying, classes of, 313–314
and psychiatric illness, 431
Behavior observation
in overt expressions of pain, 321–322
in pain measurement, 289
in psychology evaluation, 298
Behavioral activation, 1406, 1408
Behavioral approaches, in rehabilitation, 1497
Behavioral change
in pain management, 84
decisional balance in, 1471–1473, 1473t
helping patient understand importance of, 1729
importance and confidence scales in, 1729
motivation for, 1470–1479, 1728–1730
personal choice and control in, 1475
processes of, 1471, 1472t
readiness for, 1471–1472
setbacks and resistance in, 1474–1475, 1475t
SMART goals in, 1407
stages of, 1471, 1471f, 1471t
transtheoretical model of, 1471–1472
volitional approach in, 1476–1477
in psychotherapy for anger, 1400–1401
Behavioral formulations, of pain, 82–83
Behavioral interventions
for anger, 1401
for burn pain, 904–906

5501
 for cancer pain in children, 800
for children with chronic pain, 918–919
for low back pain, 1541
for substance use disorder, 1512–1513
Behavioral Observational Pain Scale (BOPS), 810
Behavioral Pain Scale (BPS), 1784, 1784t
Behavioral Pain Scale for non-intubated patients (BPS-NI), 1784
Behavioral theory, of depression, 437, 440
Behaviorism, 425–426
Beliefs, 77–78, 84–85, 296
assessment of, 322–323
in cancer and cancer pain, 600, 629
culture and, 141–143
in spine surgery candidates, 1303t, 1305
Bell, Charles, 3–4, 3f
Belladonna, for ureteral spasm, 687
Bell-Magendie law, 3–4
Bell-Magendie model, 1678
Below-level spinal cord pain, 585–587, 585f, 586f, 587f
Beneficence, 151
Benign Valsalva’s maneuver-related headache, 1028
Benoxaprofen, 1315
Benson, Herbert, 1407
Benzocaine, 737, 1386t
Benzodiazepines
abuse or misuse of, 699–700
as adjuvant analgesics, 685
for baclofen withdrawal, 1764
for cancer pain, 687, 699–700
caution with, 687
for depression, 439
for dying patients, 1737, 1739–1740, 1739t
interaction with opioid analgesics, 439, 441, 1337–1338
for local anesthetic toxicity, 887
for low back pain, 1254, 1271

5502
 medically supervised withdrawal, 1511
for muscle spasm, 1352, 1354
for noncardiac chest pain, 1054
for opioid withdrawal, 1764
for panic disorder, 442
for priapism, 969
for spinal cord injury, 589
urine testing for, 1016, 1509t
Benzydamine, for oral mucositis, 737, 740, 796
Bergman, William, 196–197
Bergman v Chin, MD, and Eden Medical Center, 196–197
Beriberi, 332
Bernstein test, 1047–1048
Best interests standard, in surrogate decision-making, 164
β-Adrenergic receptors, 118
β-Blockers
for erythromelalgia, 559
for migraine, 990t, 1133
for migraine prevention, 1023t
β-Endorphin, 48
in pregnancy, 944
in vascular occlusive crisis, 960
Betamethasone, epidural injections of, 1611
Bezold-Jarisch reflex, 1763
BFI. See Bowel Function Index
Biacuplasty, intradiscal, 1647–1648, 1648f
Bias
in clinical trials
funding source and, 130
reducing, 127–128, 128t
ethnic/racial, 140
gender, in pain treatment, 93
in pain measurement, 274
in uncontrolled studies paradigm, 123
Biased ligands, 1350

5503
Biases, as barrier to pain relief, 1725
Bier, Augustus Karl Gustav, 1385, 1386
Bier block, 1386, 1683–1684
Bieri Faces Pain Scale-Revised, 810
Bilder, Paul A., 195
Bile ducts
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Biliary colic, 1201t
Biliary sludge, in sickle cell disease, 966
Bilirubin, in sickle cell disease, 967
Billings, J. Andrew, 160
Binary concept of pain and addiction, 1003–1004
Bioethics, 151–152
Biofeedback
for cancer pain, 801
for children with chronic pain, 916, 919, 923
for complex regional pain syndrome, 353
EMG, 248–249
for noncardiac chest pain, 1055
for phantom pain, 368
for prostate pain syndrome, 1104
for rehabilitation, 1500–1501, 1500f
for sickle cell disease pain, 973
for tension-type headache, 1133
Biofield therapies, 1554–1555
Biogenic amines. See also Norepinephrine; Serotonin
in depression–pain association, 436
Biologic disease-modifying antirheumatic drugs, 492–493
Biologic response modifiers, for oral mucositis prevention, 738–739
Biologics, intradiscal, 1649–1650
Biomechanics, 1480–1489
adverse neural tension in, 1481–1482, 1481f–1483f
basic considerations in, 1480–1481
kinetic chain theory in, 1480–1481

5504
 in musculoskeletal pain syndromes, 1484–1488
neuromuscular control in, 1482–1483
in physical examination techniques, 1483–1484
Biomedical model, of rehabilitation, 1491, 1492–1493
Biophysical agents. See also specific modalities
for pain during physical therapy, 1522–1536
Biopolitics, 145
Biopower, 145–146
Biopsy, in herpes zoster, 374
Biopsychomotor model of pain, 1490, 1490f
Biopsychosocial model, 85, 90–91, 91f, 295
of chronic pain in children, 914
of ethnic differences in pain, 95–96
of gender differences in pain, 94
of interdisciplinary management, 1711
of low back pain, 1261
of rehabilitation, 1490, 1492–1493, 1492f, 1493f
Bipolar disorder, assessment for, 229–230
Bisphosphonates
for bone metastases/pain, 686, 733, 746–747, 782, 794
for calcinosis cutis, 549
for calciphylaxis, 550
for complex regional pain syndrome, 352, 353
with glucocorticoid therapy, 493
Black-blood MRA, 256, 257f
Bladder pain syndrome, 1088–1089
Bladder spasm, adjuvant analgesics for, 686–687
Bleeding, complications, 1758–1760
Bleeding disorders, neuraxial techniques contraindicated in, 853
Blind techniques, for nerve blocks, 1597
Blinding, 127
Blink reflex, 246
Blix, Magnus, 4
Block technique, for epidural analgesia, 850–851
Blood oxygen level-dependent (BOLD) fMRI, 62–63, 66–67

5505
Blood transfusion, for acute chest syndrome, 965
Blood vessels. See also specific vessels
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Blue toe syndrome, 569
Board certification, for pain specialists, 1751–1752, 1752f, 1753f, 1793
Body awareness therapy, 1551
Body perceptions, altered, 229
Body scan meditation, 1407–1408
Body system-based classification, 16
Body temperature, opioid analgesics and, 1338
Boerhaave syndrome, 1195t
BOLD. See Blood oxygen level-dependent (BOLD) fMRI
Bombesin, 46t, 48
Bone and Joint Decade, 484
Bone marrow expansion, pain from, 748, 795
Bone marrow infiltration, 793
Bone marrow transplant, for sickle cell disease, 977
Bone metastases, 644–651. See also Bone pain, in cancer
imaging of, 647
Karnofsky performance status in, 648–649, 650t, 769–770, 769f
mechanisms of, 647, 649f, 650f
pathologic fracture in, 649–650, 651f, 770–772, 771f
prognosis of, 648–649, 650t
Bone pain, in cancer, 616, 634, 644–651, 686, 744–750, 765
adjuvant analgesics for, 747
associated processes, 748
bisphosphonates for, 686, 733, 746–747, 782
calcitonin for, 686, 747
characteristics of, 647–648
in children, 793–794, 797
costs of, 765
COX-2 inhibitors for, 746
epidemiology of, 744, 744t
evaluation of, 745, 765

5506
 G-CSF and, 651, 795
GM-CSF and, 748
hormonal therapy for, 747
image-guided ablation for, 729
metastatic spinal cord compression and, 772–776
NMDA antagonists for, 747
opioids/opiate antagonists for, 747
pathophysiology of, 744–745
procedural interventions for, 747–748
radiation therapy for, 765, 767–778, 769f, 770
for diffuse metastases, 776–778
metastasis response in, 767–768, 768t
pathologic fracture in, 770–772, 771f
reirradiation in, 770
stereotactic, for nonspine metastases in, 770
for vertebral metastases (spinal cord compression), 773–776, 775f
wide-field, 776–777
radiopharmaceuticals for, 747, 765, 777–778, 777t
treatment of, 746–748, 765
tumor infiltration and, 637
Bone scan, 745, 772, 774f
Bonica, John, 7–8, 8f, 9, 1794
on behavioral therapies, 1405
on deficiencies in pain education, 153
development of pain medicine, 1751–1753
on multidisciplinary approach, 7–8, 9, 1490, 1709, 1717, 1751
BOPS. See Behavioral Observational Pain Scale
Bornholm disease, 1190, 1195t
“Borrowing from tomorrow to pay for today,” 1012, 1013, 1014
Botulinum toxin
for central pain, 401t
for migraine, 990t, 1133
for myofascial pain (trigger points), 517
for neuropathic pain, 686t
for noncardiac chest pain, 1054, 1055f

5507
 for phantom pain, 366–367
for postherpetic neuralgia, 385t, 389
for postsurgical breast pain, 1191
for sciatic nerve entrapment, 1217
for spinal cord injury, 589–590
for thoracic outlet syndrome, 578, 579
for trigeminal neuralgia, 1114–1115
Bouchard’s nodes, 487, 488f
Boulogne, Duchenne de, 1109
Bowel dysfunction
cancer and, 617
opioid-induced, 682–683, 697t, 1341
in cancer patients, 617
in children, 816–817, 817t
in elderly patients, 933
μ-opioid receptors in, 1333–1336
tolerance to, 1338–1339
treatment of, 683, 1341
Bowel Function Index (BFI), 682
Bowel syndrome, narcotic, 1069
BPI. See Brachial plexus injury; Brief Pain Inventory
BPS. See Behavioral Pain Scale
Brachial plexopathy, 1138, 1175–1176
in cancer, 654–655, 655t
differential diagnosis of, 655, 656t
imaging of, 655, 655f
Brachial plexus, 1146–1150
formation of, 1146–1147, 1147f
lesions of, 1160, 1176, 1175t
magnetic resonance neurography of, 262
organization and branches of, 1147–1148, 1148f, 1148t
Brachial plexus block
axillary, 861–862
facilitating function with, 1607
infraclavicular, 820, 859–861

5508
 interscalene, 857–858
supraclavicular, 820, 858–859
suprascapular, 862–863, 1607
terminal branch, at elbow and below, 863–866
Brachial plexus decompression, for thoracic outlet syndrome, 579
Brachial plexus injury (BPI), 1175
Brachial plexus neuritis, acute, 1176
Brachial plexus stimulation, 1564
Brachial plexus tension test, 577
Brachialgia cord syndrome, 1170t
Brachytherapy, for trachea, bronchi, and lungs, 766
Bradycardia, fetal, neuraxial analgesia and, 949
Bradykinesia, in complex regional pain syndrome, 345
Bradykinin
in cancer pain, 627, 732–733
in myofascial pain (trigger points), 508–509, 511, 512–513
in spinal nociceptive processing, 49
in stress, 419–420
in vascular occlusive crisis, 960
Braid, James, 1421
Brain. See also specific structures and functions
anatomy of, 62, 62f
plasticity of, 14, 71–72, 1424
Brain damage, malpractice claims over, 1758, 1759f
Brain metastases, palliative radiation therapy for, 767
Brain stimulation, 57, 63, 1587–1591. See also Deep brain stimulation;
Motor cortex stimulation
Brain tumors
central pain with, 398
in children, 793
sleep disturbance with, 632
Brain-derived neurotrophic factor (BDNF), 46t, 48, 50
Brainstem, 62, 62f, 63–64
ablative procedures for, 1704–1705
anatomy and physiology in, 1704–1705

5509
 indications for, 1704
outcomes of, 1705, 1705t
techniques of, 1705
autonomic centers in, 114
mesolimbic dopamine system in, 64
spinal connections to, 65
thermal RF procedures for, 1657
vertical zones of, 63
Breach of duty, 193
Breakthrough cancer drugs, 779
Breakthrough pain
in burn injury, 898
in cancer, 13, 644, 681
definition of, 13
immediate-release medications for, 1013
Breast cancer, 641
brachial plexopathy in, 654, 655f
chemotherapy for, 780
epidemiology of, 622f, 641
fatigue in, 631–632
hormonal therapy for, 782
pain in, 622–623, 641
bone metastases and, 634, 641, 744–747, 744t, 772–773, 776
causes of, 641, 642t
chest wall, 1182, 1200t
postmastectomy, 657, 1190–1191, 1200t
tumor type and stage of disease in, 638
postoperative frozen shoulder in, 748
sleep disturbance with, 632
spinal cord compression in, 661, 772–773, 776
Breast pain, 1190–1191, 1199t–1200t
Breath pattern retraining, 1551
Breathing techniques, 1500, 1500f
“Breathless epochalization,” 137
Breitbart, Bob, 1751

5510
Breyer, Stephen, 201
Bridenbaugh, Philip, 1751
Brief Hospice Inventory, 1734
Brief Pain Inventory (BPI), 129, 227, 232, 285, 321, 930, 992
for cancer pain, 601, 603, 606f–607f
for dying patients, 1733
for GERD-related chest pain, 1051
in intrathecal drug trialing, 1630
Brief Pain Inventory Pain Interference Scale, 286–288, 323
Brief psychosocial screening (ACT-UP), 319, 319t
Brief Symptom Inventory, 915
Brief Symptom Inventory-Depression scale, 630
Brief-intense stimulation, 1526–1527
British Medical Association, 1421
Brivudin, for herpes zoster, 377–378, 377t
Brodmann, K., classification of cortex, 65
Bromfenac, 1315
Bronchi
autonomic stimulation of, 119t
palliative radiation therapy for, 766
sympathetic and nociceptive nerve supply to, 115t
Bronchial cancer, epidemiology of, 621, 622f
Bronchiectasis, 1194t
Bronchogenic carcinoma, 1195t
Bronfenbrenner’s systems theory, 1495
Brown-Séquard, Charles-Édouard, 4
Brown-Séquard syndrome, 1169t
Bruns-Garland syndrome, 335
Brushwood, David, 178
Buccal route, for end-of-life drug delivery, 1735
Budapest criteria, for complex regional pain syndrome, 347, 347t
Buerger’s disease, 570, 571f
Buffering, of local anesthetics, 1386–1387
Bullous dermatoses with erosions, 556–558
Bullous pemphigoid, 557–558, 557f

5511
Bunion deformity, 1222–1223, 1222f
Bupivacaine, 1386t
for acute pain
epidural, 834
epidural, for children, 818–819, 819t
intra-articular, 837
for childbirth pain
combined spinal-epidural, 947t, 948–949
epidural, 947, 949t
chirality of, 1382–1383
dosing in nerve blocks, 888t
intradiscal, 1649
intrathecal, 714t, 715, 1375, 1625t, 1626, 1631t
for phantom pain prevention, 364–365
prolonged-duration, 1389
for sensory mononeuropathies, 559
systemic toxicity of, 1761–1763
for thoracic outlet syndrome, 578, 579
for trigeminal neuralgia, 1115
Buprenorphine, 1335t, 1346
for acute pain
intravenous patient-controlled, 832t
in opioid-tolerant patients, 840–841
androgen deficiency with, 1338
buccal, 1342
for cancer pain, 690t, 695
for cancer pain in children, 798
for elderly patients, 933
extended-release, 690t
for fibromyalgia, 538
hepatic dysfunction and, 689t
interaction with antiretroviral therapy, 995t
for maintenance treatment, 178, 1511–1512, 1513, 1515–1516
metabolites of, 1348t
for opioid use disorder, 454

5512
 as partial opioid agonist, 1335t, 1336
perineural, 853–854
respiratory depression with, 1338
sublingual, for addiction, 1008–1009
transdermal, 1342
urine testing for, 1509
Bupropion, 337, 439
Burn pain, 897–908
anatomical considerations in, 897, 897f
background, 903
behavioral interventions for, 904–905
breakthrough, 898
in children, 899
cognitive interventions and coping styles in, 903–904
drug-seeking behavior in, 905
generalized treatment paradigm for, 900–901
hypnosis for, 905, 1429
long-term neuropathic, 900
nature of, 897–899, 897f, 898f
nonpharmacologic approaches for, 903–906
pharmacologic approaches for, 901–903
postoperative, 898, 903
preparatory information on, 904
procedural, 897–898, 902–903
psychological factors in, 899–900
resting, 898
sedation guidelines for, 900–901, 900t, 901t
substance abuse in, 899, 905
virtual reality for, 905–906, 906f
Burning perineum syndrome, 757
Burst spinal cord stimulation, 1573–1574, 1573f
Burst train, in TENS, 1527, 1573
Burt, Robert, 159
Buspirone, for anxiety, 441
Butorphanol, 1334t, 1346

5513
 avoidance in cancer pain, 696
for burn pain, 902
in emergency department, 1776
metabolites of, 1348t
respiratory depression with, 1338
Butterbur, for migraine prevention, 1023t

C
C fibers, 26, 38, 41, 42f, 106, 107
in acute pain, 827, 831
in cancer pain, 647–648, 732–733
in childbirth pain, 941
complex regional pain syndrome and, 343
in cutaneous sensation, 543
in elderly, 839
in emotion, 414
in neuraxial analgesia, 853
neuropathy and, 330
in peripheral nerve stimulation, 1558–1559
postherpetic neuralgia and, 382–383
spinal cord injury and, 110
in spinal cord stimulation, 1571, 1572f
wind up of, 15, 45, 53, 53f, 107, 236
C1 cell group, in descending modulation of pain, 55
Cachexia, in cancer, 617
Caffeine
for hypnic headache, 1028–1029, 1134
for low CSF volume headache, 1030
for tension-type headache, 1133
CAGE-AID, 227, 231, 610, 610t, 700, 1006, 1006t
Cairns, Hugh, 1701
Calcinosis cutis, 549
Calciphylaxis, 549–550, 550f
Calcitonin
for bone pain, 686, 747
for complex regional pain syndrome, 352, 353

5514
 for phantom pain, 366
Calcitonin gene-related peptide (CGRP), 33, 41, 45–48, 46t, 106
in acute pain, 827
in cutaneous sensation, 543
in migraine, 1023, 1024
in myofascial pain (trigger points), 508, 509, 511, 512, 512f
in spinal cord stimulation, 1571
in synaptic action, 107
in vascular occlusive crisis, 960
Calcitonin gene-related peptide antagonists, intrathecal, 1629
Calcium channel(s)
in migraine, 1019–1020
in muscle physiology, 506–508, 507f
N-type, 50
voltage-gated, 31–32, 50
Calcium channel blockers
for abdominal pain (IBS), 1071
for cluster headache, 1134
intrathecal, 1627
for noncardiac chest pain, 1052
T-type, for cancer pain, 757
Calcium pyrophosphate deposition disease (CPPD), 497
California
litigation over pain management in
administrative proceedings, 195
civil, 196–198
criminal, 199
medical marijuana in, 202
physician education on pain in, 153
physician-assisted death in, 202
Callahan, Daniel, 161
Canada, topical NSAIDs in, 1319t
Canadian C-Spine Rules, 1168, 1168f, 1231, 1232, 1232f
Canadian Pain Society, 1375
Canadian Supreme Court, ruling on physician-assisted death, 202

5515
Cancer
comorbidities in, 601
death and survival rates in, 621–622, 621f, 624f
delirium in, 616–617
depression in, 629–631
disease trajectory of, 599
epidemiology of, 621, 621f, 622f, 623f, 624f
immunotherapy for, 779
nausea and vomiting in, 617
antiemetics for, 683–684, 684t, 687
chemotherapy-induced, 683, 684, 701
opioid-induced, 683–684, 684f
radiation therapy–induced, 683
nonpain pathophysiology of, 678
palliative care in, 763–765, 764f, 802–803
patient anxiety and stress in, 622
pediatric, 788
epidemiology of, 788
palliative care in, 802–803
survivorship in, 788
treatment of, 788
primary treatment of, 678–679
risk factors for, 599
sleep disturbance in, 630, 632–633
stenting, drainage procedures, and antibiotics in, 679, 679f
surgery for, 678–679
symptom clusters in, 618
tumor markers in, 643, 644t
vertebral augmentation in, 725–727, 726f
Cancer Care Ontario, 782
Cancer Fatigue Scale, 632t
Cancer pain
accompanying symptoms with, 608t, 609
acetaminophen for, 682
in children, 793, 797–798

5516
activities of daily living in, 664
acute, 636, 636t
adjuvant analgesics for, 685–687
bone pain, 686
definition of, 685
general purpose, 685
musculoskeletal, 685
neuropathic, 685–686
visceral, 686–687
affective processing and suffering in, 602–603, 628–629
age-specific needs in, 600
anesthetic model of, 616
around-the-clock regimens for, 678, 681, 689–690
assessment and diagnosis of, 613–616, 621–675
associated symptoms, 666–667
in children, 790–792
clinical status of patient in, 665, 667t
comprehensive, chronic pain, 602
general, 665
issues in, 623–625
laboratory and imaging data in, 667
monitoring disease status in, 665, 667t
Pain Disability Index in, 664, 665t
pathophysiologic, 615
provisional diagnosis in, 667
quality of life, 664
skills and knowledge for, 625
stepwise approach to, 663–667
syndrome, 613–615, 644, 645t–647t
validated tools for, 603, 604f–607f
back, 613
barriers to management, 623–625
bone (See Bone pain, in cancer)
breakthrough, 13, 644, 681
cannabinoids for, 687

5517
chemotherapy in, 763–765, 778–782
clinical applications of, 779–780
side effects and complications of, 782
in stable disease, 780
chest or chest wall, 642, 721–722, 722f, 1182–1184
in children, 600, 788–808, 821–822
adult pain v., 788–789
cancer history—diagnosis in, 791
cancer history—treatments in, 791–792
disease-related, 793–794
emotional and cognitive experience, 790–791
epidemiology of, 789
etiologies of, 793–797
evaluation of, 790–792
expressive arts therapies for, 800–801
functional and quality-of-life assessment in, 791
history and physical exam in, 790
incorporating technology in assessment of, 792
infants–preschoolers, 788
infectious causes of, 796–797
integrating data in evaluation of whole child, 792
management of, 797–803
neuropathic, 796, 799
opioids for, 795–796, 798–799, 821–822
past medical, psychiatric, social, and spiritual history, 792
past pain-directed therapies in, 791
pharmacotherapy for, 797–799
physical and psychological therapies for, 799–802, 799t
procedure-related, 794–795
proxy reports of, 792
school age–adolescence, 788–789
sensory experience–observation, 790
sensory experience–self-report, 790
in survivorship, 797
treatment-related, 795–796

5518
 undertreatment of, 789–790
WHO guidelines on, 797–798
chronicity of, 636
cingulotomy for, 1701–1703, 1702t
classification of, 635–638, 635t
clinical practice guideline on, 173
cognitive-behavioral therapy for, 739
in children, 800
compared with other sources of pain, 622–623
complementary and integrative health in, 701–702
complementary clinical perspectives in, 615–616, 616f
cordotomy for, 727–728
definition of, 11, 12
dermatomal, 602, 612
disease-related (extent of disease), 599
dorsal rhizotomy or ganglionectomy for, 1680–1681
dorsal root entry zone lesioning for, 729
drug list for, 680t
emergencies in, 618–619
end-of-life, 618, 1732–1733
epidemiology of, 205, 599–602
ethnicity and, 600
exacerbating/relieving factors in, 664
familial, vocational, and social function in, 664
fluctuating, 608
focality of, 608–609, 608t
history of, 602–603, 609–610, 663–664, 663t
home infusion therapy for, 701
hormonal therapy for, 747, 782
hypnosis for, 800, 1431
IASP global year against, 676
impact of, 664
improving, 608
individual perception of, 629, 629f
in inmates, 601–602

5519
intensity/severity of, 636, 664
intermittent episodes of, 608
interventional therapies for, 679–680
intrathecal drug delivery for, 711–716, 711t, 714–716, 714t, 1639–1640
indications for, 712
outcome studies of, 713–714
pharmacology in, 714–715, 714t
risk management in, 715
location of, 663–664
management of, 616–619, 676–710
approaches in, 676–677, 677t
attention to detail in, 681
clinical practices guidelines for, 677
guidelines for, 676
history of substance abuse and, 617–618
individual factors in, 681
multimodality, 677–678, 678f
overview of, 677–679
primary treatment and, 678–679
symptomatic, 679–681
tumor pain algorithm for, 679f
tumor-directed, principles of, 678
UN recommendations on, 219
universal precautions in, 617–618
WHO algorithm for, 676
WHO analgesic ladder in, 208, 676, 677, 679–681, 680f, 711, 738
manifestations, prevalence and etiologies of, 648t
medical model of, 615
medication history in, 610, 610t
mixed, 603
multidimensional nature of, 629
myelotomy for, 728–729
myofascial, 613, 627–628
myotomal, 602, 613
neurolysis for

5520
 celiac plexus, 711, 711t, 717–719, 718f
ganglion of impar, 720–721, 720f, 759
spinal, 711t, 716–717, 716f
superior hypogastric plexus, 711t, 719–720, 719f, 720f
neuropathic, 603, 625–626, 628, 653–661
chemotherapy and, 635, 635t, 659–660, 660t, 685–686, 689, 751
in children, 796, 799
diagnosis of, 613–614, 615t, 623–625
etiology of, 626, 626t
in head and neck cancer, 733
imaging findings in, 625, 626f
management of, 685–686, 689
nociceptive pain v., 636
postsurgical, 657–658
presenting complaint in, 609
progression of, 608
referred, 602
secondary to cranial nerve pathology, 653–657
secondary to therapeutic interventions, 657–661
nociceptive, 613–614, 615t, 625–626, 636
nonnociceptive, 614–615, 615t
nonsteroidal anti-inflammatory drugs for, 681, 686
in children, 793, 797–798
onset of, 608, 608t, 663
opioid analgesics for, 205, 676–677, 682–684, 687–700
active treatment v. chronic pain, 689
bowel dysfunction with, 682–683
buprenorphine, 690t, 695
in children, 795–796, 798–799, 821–822
codeine, 695–696
diversion of, 619
drugs not recommended, 696
in elderly patients, 689
extended-release, 690, 690t
fentanyl, 689, 690, 690t, 693–695, 698–699

5521
 history of abuse and, 617–618
hydrocodone, 690t, 695
hydromorphone, 690t, 691–692, 698–699, 821–822
international initiatives on, 220
intracerebroventricular, 699
levorphanol, 692–693
methadone, 689, 692, 698–699, 821–822
misuse or abuse of, 699–700, 700t
morphine, 689, 690t, 691, 698–699, 821–822
for mucositis-related pain, 738, 795–796
nausea and vomiting with, 683–684, 684f
newer derivatives, 758–759
oxycodone, 689, 690t, 691, 821–822
oxymorphone, 691
parenteral, 698–699
risk evaluation and monitoring for, 665, 667t, 700, 700t
rotation of, 698, 698t, 799
selection of therapy, 687–690
short- v. long-acting, 689–690, 696
side effects of, 617, 682–683, 696–697, 697t
tapentadol, 690t, 696
tolerance and hyperalgesia with, 690–691
tramadol, 696
transdermal, 690, 690t
oral medications for, 679, 680
pain in cancer patient v., 625
palliative care for, 205, 615
pathophysiologic changes and, 647t
pathophysiology of, 636–638
patient experience of, 626–627
in patients with substance use disorder, 464–465
patterns of, 644
performance status in, 648–649, 650t, 664, 665t, 769–770, 769f
peripheral neurectomy for, 1672
pharmacologic principles for, 680, 681t

5522
pharmacologic strategies for, 680–681, 680t
physical examination in, 610–613, 665, 667
bedside provocative maneuvers in, 611–613, 612t
general, 610–611
regional, 611, 611t
presenting complaint in, 608–609, 634, 638
prevalence of, 634
progression of, 608, 608t
progressive, 608
psychological factors and, 629, 664
psychotropic drugs for, 687
quality of, 664
radiation therapy for, Karnofsky performance states and survival in,
769–770, 769f
radiation therapy in, 763–778
for bone metastases, 747, 767–778
clinical applications of, 766
curative v. palliative, 766
single-fraction, 768–770
tumor response in, 766–768
rehabilitative model of, 615
response to previous therapies in, 664
sclerotomal, 602, 612–613
somatic, 603, 613–614, 615t, 626, 627–628
sources of, 625, 634–635, 634t
spinal cord ablation for, 727–729
spinal cord stimulation for, 725
substance abuse in, 601, 610, 610t, 617–618, 699–700, 700t
timing of, 664
treatment-related, 599, 635, 646t, 657–661
tumor type and stage of disease in, 638–644
tumor-related, 625–627, 637–638
CNS mechanisms of, 626
encapsulated organs and, 637
infiltration and inflammation of serous mucosa, 638

5523
 infiltration of abdominal hollow organs and, 637–638
infiltration of bone and, 637
infiltration of peripheral nerves and, 637
infiltration of sacrum and sacral nerves and, 656
infiltration of soft tissues and, 637
infiltration of viscera and, 651, 652t
molecular mechanisms of, 627
PNS mechanisms of, 626
types of, 603–608, 613–615, 615t
undertreatment of, 623, 676, 676t
unrelieved, consequences of, 676
visceral, 603, 613–614, 615t, 625–626, 628, 651–653
chemotherapy and, 756, 757
in children, 793
descriptions by site, 652–653
diagnosis of, 623–625
inflammatory, 751–752
ischemic, 751–752
localization of, 652
mechanical, 751–752
mechanism of, 651–652
pain syndromes in, 754–757
pharmacotherapy for, 757–759
procedural interventions for, 759–760
radiation therapy and, 756–757
surgery for, 759–760
treatment of, 757–760
true v. referred, 652
Cancer Pain Management Policy Review Group, 173
Cancer Pain Relief (WHO), 219
Cancer pain syndromes, 613–615, 626, 634–635, 644, 645t–647t, 754–757
Cancer Prevention and Control (WHA), 219
Cancer-related fatigue (CRF), 630, 631–632, 632t
Candesartan, 990t, 1023t
Candida infections

5524
 in cancer treatment, 738, 754
in HIV/AIDS, 986, 987
Candidate genes, in pain, 96–97
Cannabinoids
for cancer pain, 687
for cancer pain in children, 801
for central pain, 401t
drug delivery for, 1369
for fibromyalgia, 537, 537t
for HIV pain, 996
for nausea/vomiting in cancer therapy, 684
for neuropathic pain, 1369–1370, 1371t
for painful neuropathies, 337
for postherpetic neuralgia, 388
for spinal cord injury pain, 592
U.S. Supreme Court decision on medical marijuana, 201, 202–203
Cannabis, 1369–1370, 1371t. See also Cannabinoids; Marijuana
Caphosol, for oral mucositis, 740
Capital extensors of neck, 1152t
Capital flexors of neck, 1141, 1152t
Capital movers of neck, 1141
Capsaicin, 1356–1357
as adjuvant analgesic, 685
for chronic pelvic pain, female, 1086
for complex regional pain syndrome, 353
for elderly patients, 933–934
for HIV pain, 996
for neuropathic pain, 686t, 1369, 1370t
for painful neuropathies, 337–338
for phantom pain, 366
for postherpetic neuralgia, 385t, 388, 685, 1118, 1186
for sensory mononeuropathies, 559
CAPTE. See Commission on Accreditation in Physical Therapy Education
Carbamazepine
for acute pain, 830–831

5525
 for central pain, 400, 401t
for complex regional pain syndrome, 352
for elderly patients, 933
for erythromelalgia, 559
for Fabry’s disease, 560
in intensive care unit, 1787
for neuropathic pain, 400, 1362–1365, 1363t, 1367
for painful neuropathies, 337
for phantom pain, 365
for spinal cord injury pain, 591
and Stevens-Johnson/TEN syndrome, 556
for trigeminal neuralgia, 1113–1115, 1691, 1692
for vagal neuralgia, 1122
Carbonic anhydrase inhibition, 1031
Carbuncles, 553–554, 553f
Cardiac chest pain, in HIV/AIDS, 987
Cardiac disease, spinal cord stimulation for, 1191, 1575–1576, 1577f
Cardiac nerves, 753
Cardiac plexus, 111
Cardiac surgery, pain after, 1191
Cardiac toxicity, of local anesthetics, 887–888
Cardiology evaluation, for chest pain, 1041–1042
Cardiomyopathy, hypertrophic, 1193t
Cardiovascular effects
of NSAIDs, 1324–1326, 1325f, 1325t, 1326f
of opioid analgesics, 1341, 1344
of pregnancy, 943–944, 943f, 943t
CARES approach, 792
CARF. See Commission on Accreditation of Rehabilitation Facilities
Caries, 1130–1131, 1130f
Carisoprodol, 685, 1352t, 1354
Carnett’s maneuver, 613, 614f
Carnett’s sign, 1064
Carnochan, J. M., 1109
Carotid tubercle, 1163

5526
Carpal tunnel syndrome (CTS), 264, 267, 1174–1175, 1673–1676
clinical features of, 267
diagnostic imaging in, 267, 268f
electrodiagnostic tests in, 249, 1175, 1673–1674
nerve entrapment release for, 1673–1676
rheumatoid arthritis and, 491, 493, 1175
Carr, Daniel, 173, 1751
Carron, Harold, 1751
Carryover effects, 131
Cartesian theater, 410
Cartilage disorders, 558–559
Case management, 1495
Case manager/coordinator, 1712
Case series, 123–124
Cassell, Eric, 152, 154, 155
Catalepsy induction, 1432
Catastrophic neural injuries, 1765–1767
Catastrophizing, 13, 78, 142, 225, 296, 1405
in abdominal pain, 1067, 1070
assessment of, 227, 230, 296, 323, 915
in children, 915
cognitive distortions and, 437–438
definition of, 230
in failed back surgery, 1293
in female pelvic pain, 1084–1085
group therapy and, 1456, 1461
in male pelvic pain, 1103
neural substrates of, 419
shifting focus and, 1476
in spine surgery candidates, 1301, 1305
Catecholamines, in myofascial pain (trigger points), 511–512
Catechol-O-methyl transferase (COMT), 96, 97, 1067
Catheter(s)
interpleural, for cancer pain, 759
for intrathecal drug delivery, 712

5527
 peripheral nerve, 856–857
Catheter problems, in intrathecal drug delivery, 715, 1634t, 1636
Cauda equina syndrome, 495
Caudal analgesia, 1385
for childbirth pain, 947t, 949–950
Caudal epidural steroid injections, 1611, 1612–1613
adverse events in, 1613
evidence on, 1612–1613
technique of, 1612, 1612f, 1613f
Causalgia. See Complex regional pain syndrome
CBAT. See Cognitive-behavioral affective therapy
CBF. See Cerebral blood flow
CBT. See Cognitive-behavioral therapy
CCBT. See Contextual cognitive-behavioral therapy
CDC. See Centers for Disease Control and Prevention
Cebranopadol, 758–759, 1374
Cecum, sympathetic and nociceptive nerve supply to, 116t
Ceftriaxone, for gonococcal arthritis, 501
CEH. See Cervicogenic headache
Celecoxib, 1316t, 1322–1323
for acute pain, 830
cardiovascular effects of, 1324–1326
for children, 812t
for elderly patients, 932
for osteoarthritis, 1322
relative efficacy of, 829t, 830
Celiac ganglion, 113f, 114
Celiac ganglion neurolysis, 1654
Celiac plexus, 717
Celiac plexus neurolysis, 711, 717–719
adverse effects of, 717–718
general considerations in, 717
indications for, 717
outcome studies of, 719
techniques of, 718–719, 718f

5528
Cell bodies, of spinal cord, 39
Cellular dehydration, in sickle cell disease, 957–958
Cellulitis, 553, 553f
Center for Epidemiologic Studies Depression Scale (CES-D), 630–631,
631t
Center of excellence, 1720
Centers for Disease Control and Prevention (CDC)
on benzodiazepine use, 439
HIV reporting, 985
on immediate-release medications, 1013
on nonpharmacologic and nonopioid therapy, 1405–1406
opioid dose calculator, 829
opioid guidelines of, 1008, 1504, 1724, 1744, 1747, 1764
Centers for Medicare & Medicaid Services, 1522
Centers for Occupational Health and Education, Washington State, 308–
309
Central canal, of spinal cord, 39, 41
Central cord syndrome, 1169t
Central mediated abdominal pain syndrome (CAPS), 923
Central nervous system
autonomic centers in, 114–118
descending pathways of, 108–109
emotion and, 412, 412f
functional anatomy of, 106–110
NSAIDs and, 1328
opioid analgesics and, 1336–1341
depressive effects, 1336–1338
excitatory effects, 1338
pain causes in (See Central pain)
processing function of, 107
regulatory function of, 107
tumors, in children, 793
Central nervous system disorders, neuraxial analgesia in, 853
Central pain, 13, 109–110, 396–409
analgesic adjuvants for, 853–854

5529
 clinical assessment of, 397–398, 398t
clinical characteristics of, 397
conditions included in, 109, 396, 398–399
definite (confirmed), 396f, 397
definition of, 396
descriptors of, 110
diagnosis of, 396–397
disinhibition hypotheses of, 399–400
grading system for, 396–397, 396f
mechanisms of, 399–400
possible, 396, 396f
preclinical models of, 399
probable, 396f, 397
sensory abnormalities in, 397, 397f
spinal cord injury and, 109–110, 398–405
treatment of, 400–404
algorithm for, 402f
challenge of, 400
neuroablation for, 403
neuromodulation for, 403–404
neurosurgical, 403–404
pharmacologic, 400–403, 401t, 402f
psychological and physiotherapy, 403
targeted drug delivery for, 403
underdiagnosis of, 109
Central pain syndromes, in cancer, 656
Central poststroke pain (CPSP), 398–405, 570
mechanisms of, 399–400
neuroablation for, 403
neuromodulation for, 403–404
pharmacotherapy for, 400–403, 401t
Central sensitivity syndromes, 527
Central sensitization, 13, 32, 45, 53, 54f
in abdominal pain, 1062, 1066
assessing/inferring, 235, 318

5530
 in central pain states, 397, 399
in children, 913, 915–916
in fibromyalgia, 527–528, 528t, 529
in hyperalgesia, 58
in myofascial pain (trigger points), 509–511
in noncardiac chest pain, 1039
in pelvic pain
female, 1089
male, 1096, 1099, 1100
in postherpetic neuralgia, 382–383
prevention of, 827–828
in unexplained pain syndromes, 525
Central α2 agonist muscle relaxants, 1352t, 1355
Central spine stenosis
in failed back surgery, 1290, 1291–1292, 1295
treatment of, 1295
Cephalexin, for cellulitis, 553
Cephalosporins, for infectious arthritis, 501
Ceramide/sphingosine 1-phosphate system, 33
Cerebellum, 45, 62, 62f, 108
Cerebral blood flow (CBF), imaging of, 62–63
Cerebral cortex. See Cortex (cerebral cortex)
Cerebrospinal fluid (CSF)
hypertension, 258
hypotension, 257–258, 258f
increased pressure, headache with, 1030–1031
low volume, headache with, 1030, 1030f
pregnancy and, 944
Cerebrospinal fluid leak, 1635
Cerebrum, 62, 62f
Certificate of Added Qualifications in Pain Management, 1752
Certolizumab, for rheumatoid arthritis, 492–493, 492t
Cervical canal, 1142, 1144f
Cervical cancer, 639–640
Cervical disk(s), 1138–1139, 1139f

5531
 degeneration of, 1139, 1168–1170
hydraulic mechanism of, 1139, 1140f
Cervical disk stimulation, 1234, 1234f, 1237, 1237f
Cervical enlargement, 1142
Cervical facet pain, 1485
Cervical fractures, 1231, 1232f
Cervical ganglia, 112, 113f, 1143–1145, 1145f, 1146f
Cervical medial branch blocks, 1234, 1235f, 1602–1603, 1602f, 1603t
Cervical medial branch neurotomy, 1172, 1238–1239, 1239f, 1660–1662
background of, 1660–1661
efficacy of, 1662
technique of, 1661, 1661f
Cervical myelopathy, 1138, 1162–1163, 1169–1170
Cervical nerve(s), 1138, 1143–1150, 1144f, 1145f, 1146f
dermatomes of, 1145, 1147f, 1150f
myotomes of, 1145, 1150f
sclerotomes of, 1145, 1150f, 1152t
Cervical nerve block, 1598f, 1599–1600
Cervical neurolysis, 717
Cervical plexopathy, in cancer, 653
Cervical plexus, 1146
deep branches of, 1146
formation of, 1146, 1147f
lateral branches of, 1146, 1147f
lesions of, 1160
medial branches of, 1146, 1147f
origin and composition of, 1146, 1147f
superficial or cutaneous branches of, 1146, 1146f
Cervical radiculopathy, 1138, 1161t, 1172–1173, 1485
Cervical spine
anatomy of, 1138–1141, 1139f, 1144f
inspection and palpation of, 1163–1164
ligaments of, 1140–1141, 1142f
lumbar spine v., 1140t, 1141f
nerve supply to muscles of, 1152t

5532
 pain
dorsal rhizotomy or ganglionectomy for, 1680
neck pain defined as, 1230, 1230f (See also Neck pain)
of unknown origin, 1233
radiographic studies of, 1168–1169, 1167t, 1168f
referred pain from, 1230–1231, 1230f, 1231f
Cervical spine disease. See also specific disorders
chest wall pain in, 1200t–1201t
neck and arm pain in, 1158
in rheumatoid arthritis, 493
Spurling’s test in, 577, 611–612, 612f, 653, 1165
Cervical spondylosis, 1138, 1168–1170
Cervical spondylotic myelopathy (CSM), 1169–1170
classification systems for, 1170, 1170t
differential diagnosis of, 1169–1170
magnetic resonance imaging in, 1170
treatment of, 1170
Cervical sympathetic blocks, 1600
Cervical transforaminal injection
anatomy in, 1765, 1766f
complications of, 1765–1767, 1767f
Cervical vertebrae, 1138–1141, 1140f
Cervical zygapophysial joint pain, diagnostic nerve blocks for, 1602–1603,
1602f, 1603t
Cervicalgia, biomechanical considerations in, 1484–1485
Cervicogenic headache, 1031, 1138, 1171–1172, 1231, 1236–1238
anatomic basis of, 1171
definition of, 1171
diagnosis of, 1171–1172, 1236
diagnostic criteria for, 1171, 1171t, 1236, 1236t
differential diagnosis of, 1236
epidemiology of, 1170
inspection and palpation in, 1164–1165
minimally invasive tests in, 1237, 1237f
prevalence of, 1237–1238

5533
 sources of, 1236
treatment of, 1239–1240
Cervicogenic Headache International Study Group (CHISG), 1171, 1171t
CES-D. See Center for Epidemiologic Studies Depression Scale
c-fos, in neuronal characterization, 38–39, 64
CGRP. See Calcitonin gene-related peptide
Change
behavioral (See Behavioral change)
stages of, 1400–1401
Channelopathies, 1020
Charcot, Jean-Martin, 1421
Charcot spine, 589
Charcot-Marie-Tooth syndrome, 329, 330, 332
Charlin’s (nasociliary) neuralgia, 1122–1123
Charon, Rita, 143
Chemical dependency, 184
Chemical neurolytic blockade, 711t, 716–717, 716f, 1653, 1654
Chemical sensitivity, of nociceptors, 24
Chemokine receptor type 2 antagonists, for cancer pain, 758
Chemotherapy
adjuvant, 778
in cancer pain management, 763–765, 778–782
clinical applications of, 779–780
decision making about, 781–782
side effects and complications of, 782
in stable disease, 780
chest pain in, 754
depression with, 630
in head and neck cancer, 733, 736, 780–781
intraperitoneal pain in, 755
intravenous, pain syndromes related to, 756
intravesical, 755–756
neoadjuvant, 778
pain mechanisms due to, 646t, 733
personalized, 779

5534
 systemic, 778
visceral pain in, 756, 757
Chemotherapy-induced nausea and vomiting (CINV), 683, 684, 701
Chemotherapy-induced peripheral neuropathy (CIPN), 635, 635t, 659–
660, 660t, 685–686, 689, 751
CHEOPS. See Children’s Hospital of Eastern Ontario Pain Scale
Chest pain
cancer-related, 642, 721–722, 722f, 1182–1184
cardiac, 1193t
chest wall, 1191
costochondritis v., 1189
in HIV/AIDS, 987
differential diagnosis of, 1191, 1193t–1202t
functional, 1034, 1035t, 1036t
noncardiac (See Noncardiac chest pain)
panic disorder and, 442
visceral, 1180
wall (See Chest wall pain)
Chest Pain Questionnaire, 1034
Chest pain syndromes
acute, in sickle cell disease, 956, 964–966
in HIV/AIDS, 987
Chest wall
anatomy of, 1180–1182
intercostal nerves of, 1181–1182, 1184f
intercostal spaces of, 1181, 1183f
joints of, 1181
skeletal structures of, 1180–1181, 1181f, 1182f, 1183f
Chest wall pain, 1180–1204, 1192f
breast, 1190–1191, 1199t–1200t
cardiac origin, 1191
differential diagnosis of, 1191, 1193t–1202t
dorsal rhizotomy or ganglionectomy for, 1680
in HIV/AIDS, 987
intercostal nerve block for, 721–722

5535
 musculoskeletal, 1180, 1180t, 1197t–1198t
myofascial, 1190, 1199t
neoplastic, 642, 721–722, 722f, 1182–1184
neuropathic, 1180, 1180t, 1184–1186, 1185t, 1196t–1197t
nonneoplastic, 1184–1191
PECS/serratus anterior plane block for, 885–886
postsurgical, 1190–1191, 1199t–1200t
psychological factors in, 1191
referred, 1191, 1192f, 1200t–1201t
skeletal, 1186–1190
rib origins of, 1188–1189, 1198t
sternal origins of, 1189–1190, 1199t
thoracic spine abnormalities and, 1184–1188, 1197t–1198t
tegumentary, 1199t–1200t
thoracic disk herniation and, 1184, 1185f
Chest wall twinge syndrome, 1190
Chest x-rays
of acute chest syndrome, 964, 964f
of thoracic outlet syndrome, 267, 578, 578f
Chevreul pendulum technique, 1432
Chiasson induction, 1432
Chicago, opioid litigation in, 199
Chicken pox, 372. See also Postherpetic neuralgia
Child Activity Limitations Interview, 914
Child Pain Anxiety Symptoms Scale, 915
Child PTSD Symptoms Scale, 914
Childbirth education, 945
Childbirth pain. See Obstetric pain
Childhood and Adolescent Migraine Prevention (CHAMP) study, 922
Childhood Arthritis Prospective Study, 909
Child-Pugh classification, 688
Children
acute pain in, 809–825
assessment of, 809–810
epidural analgesia for, 818–819

5536
 increased awareness and treatment of, 809, 809t
painful conditions in hospital care, 821–822
pharmacologic management of, 810–818
adverse experiences of, 230, 295, 1293, 1302
analgesic pharmacology in, 810–818, 916, 917–918
acetaminophen in, 810–811, 812t, 916, 917
antidepressants in, 916, 917–918
antiepileptic drugs in, 812, 812t, 916, 917–918
codeine in, 812–813, 814t
cutaneous analgesia in, 817
dosing guidelines for, 812t, 814t
fentanyl in, 814–815, 814t
hydromorphone in, 813, 814t, 821–822
ketamine in, 811–812, 812t, 822
local and regional anesthetics in, 817
meperidine in, 814t, 815
methadone in, 813–814, 814t, 821–822
morphine in, 813, 814t, 821–822
nonopioid, 810–812, 812t
NSAIDs in, 811, 812t, 916, 917
nurse-controlled analgesia in, 816
opioid, 798–799, 812–817, 814t, 821–822, 916, 917
opioid administration in, 815–816
opioid side effects in, 798–799, 816–817, 817t
oxycodone in, 813, 814t, 821–822
parent-controlled analgesia in, 816
patient-controlled analgesia in, 816, 816t
prostanoids and cyclooxygenases in, 810
tramadol in, 813
wound infiltration in, 817–818
burn injury and pain in, 899
behavioral interventions for, 904–905
distraction for, 904
cancer in, 788
epidemiology of, 788

5537
 palliative care in, 802–803
survivorship in, 788
treatment of, 788
cancer pain in, 600, 788–808, 821–822
adult pain v., 788–789
cancer history—diagnosis in, 791
cancer history—treatments in, 791–792
disease-related, 793–794
emotional and cognitive experience, 790–791
epidemiology of, 789
etiologies of, 793–797
evaluation of, 790–792
expressive arts therapies for, 800–801
functional and quality-of-life assessment in, 791
history and physical exam in, 790
incorporating technology in assessment of, 792
infants–preschoolers, 788
infectious causes of, 796–797
integrating data in evaluation of whole child, 792
management of, 797–803
neuropathic, 796, 799
opioids for, 795–796, 798–799, 821–822
past medical, psychiatric, social, and spiritual history, 792
past pain-directed therapies in, 791
pharmacotherapy for, 797–799
physical and psychological therapies for, 799–802, 799t
procedure-related, 794–795
proxy reports of, 792
school age–adolescence, 788–789
sensory experience–observation, 790
sensory experience–self-report, 790
in survivorship, 797
treatment-related, 795–796
undertreatment of, 789–790
WHO guidelines on, 797–798

5538
chronic pain in, 909–928
abdominal, 911, 923
arthritis, 909–910
back, 910, 922
background of, 912–913
barriers to care, 923
clinical evaluation of, 912–917
clinical formulation in, 915
complex regional pain syndrome, 910, 921–922
cystic fibrosis, 911
diffuse or widespread, 921
disease- or treatment-related, 911
epidemiology of, 909–911
feedback with family, 915–916
fibromyalgia, 910, 912, 916, 921
headache, 910, 922–923
history of, 913–914
impact on children and families, 911–912
intensive rehabilitation therapy for, 920
musculoskeletal, 909–910, 920–921
parent and family assessment in, 915
phantom limb, 911
pharmacologic interventions for, 916, 917–918
physical evaluation in, 915
physical therapy for, 916, 921
psychological factors in, 912, 913–914, 914–915
psychological interventions for, 918–919
school and social reintegration in, 919–920
school experience in, 914
sickle cell disease, 909, 911, 912, 919
sleep difficulties with, 912, 915, 920
specific interventions in, 917–920
temporomandibular disorders, 910
treatment principles in, 916
communication about pain, 140, 822

5539
 developmental disabilities in, 822
gender differences in pain, 92
HIV pain in, 985
hypnosis for, 800, 1429–1430
measurement of pain, 288–289, 809–810, 914–915
medical marijuana for, 801–802
medication adjustments for, 140
peripheral nerve blocks for, 819–821
sickle cell disease-associated pain in, 822
sociocultural perspective on pain in, 140–141
trauma pain in, 822
Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS), 289, 790,
810
Children’s Oncology Group, 794
Children’s Sleep Habits Questionnaire (CSHQ), 915
Chin, Wing, 196–197, 197–198
China, pain medicine in, 1754
Chinese medicine, traditional, 1552, 1553
Chirality, 1382–1383
Chiropractic medicine
AMA v., 1546
applications, methods, and results, 145, 1550–1555, 1555t
for fibromyalgia, 539
for prostate pain syndrome, 1104
CHISG. See Cervicogenic Headache International Study Group
Chlamydia trachomatis, 1080
Chlorhexidine, 555, 738, 796
Chloroprocaine, 1386t
dosing in nerve blocks, 888t
epidural, for children, 818–819, 819t
Chlorpromazine, 684t, 1739t
Chlorzoxazone, 685, 1352t, 1354
Cholecystitis, 966, 1201t
Cholecystokinin (CCK), 45, 46t, 47–48, 49, 107
in cancer pain, 733

5540
 in hyperalgesia, 58, 457
Choledocholithiasis, in sickle cell disease, 966
Cholelithiasis, in sickle cell disease, 966
Cholestasis, intrahepatic, in sickle cell disease, 967
Choline magnesium trisalicylate, 1316t
Chondrocalcinosis, 497
Chondrodermatitis nodularis helicis (CNH), 558–559
Chondroitin sulfate, 1649
Chondromalacia patellae, 488–489
Chronic compartment syndrome, 568–569
Chronic daily headache, 1021
Chronic fatigue syndrome, 445
Chronic inflammatory demyelinating polyradiculoneuropathy, 329–330,
333–334, 988–989
Chronic intestinal obstruction, 755
Chronic kidney disease
NSAIDs and, 1327–1328
stages of, 1328t
Chronic lymphocytic leukemia, 643
Chronic multisymptom illnesses, 525, 527
Chronic overlapping pain conditions (COPCs), 525, 527, 534
Chronic pain, 103. See also specific anatomy and conditions
ablative procedures for, 1698–1707
ACTTION-American Pain Society taxonomy of, 20, 21t
acute pain transition to, preventing, 1411–1412
in children, 909–928
abdominal, 911, 923
back, 910, 922
background of, 912–913
barriers to care, 923
clinical evaluation of, 912–917
clinical formulation in, 915
diffuse or widespread, 921
disease- or treatment-related, 911
epidemiology of, 909–911

5541
 feedback with family, 915–916
history of, 913–914
impact on children and families, 911–912
intensive rehabilitation therapy for, 920
parent and family assessment in, 915
pharmacologic interventions for, 916, 917–918
physical evaluation in, 915
physical therapy for, 916, 921
psychological factors in, 912, 913–914, 914–915
psychological interventions for, 918–919
school and social reintegration in, 919–920
school experience in, 914
sleep difficulties with, 912, 915, 920
specific interventions in, 917–920
treatment principles in, 916
cognitive-behavioral therapy for, 468–469, 1405–1413, 1417–1418
A-B-C model in, 1406–1407, 1407t
behavioral activation in, 1406, 1408
in children, 918–919, 923
components of, 1406–1412
evidence for, 1405–1406
group, 1439–1456, 1442–1456, 1443t–1454t
group v. individual, 1439–1442, 1440t–1441t
group v. wait-list, treatment as usual, or other group treatments,
1442–1456, 1443t–1454t
history and development of, 1405
Internet-delivered, 1442
in interprofessional pain programs, 1411
maintenance and relapse prevention in, 1406, 1409–1410
third-wave therapies in, 1405, 1410
treating comorbid conditions in, 1410–1411
compliance monitoring in, 1012–1017
communication and, 1012–1013
future considerations in, 1017
individual risk assessment in, 1012

5542
 interpreting aberrant behavior in, 1013–1014
potential treatment traps in, 1013–1014
terminating opioid therapy in, 1005–1006, 1017
urine drug testing in, 1012, 1014–1017, 1015t, 1016f
definition of, 11, 12, 1298
economic implications of, 1722
in emergency department, 1771
epidemiology of, 172, 1001, 1298
evaluation of, 225–242, 274 (See also Pain evaluation)
disability evaluation in, 302–312
general guidelines for, 226–227
multidisciplinary, 312–327
group therapy for, 1439–1469
acceptance-based, 1439, 1456–1461, 1462t
advantages of, 1463–1464
behavioral v. exercise and physical therapy, 1456
CBT v. wait-list, treatment as usual, or other group treatments, 1442–
1456, 1443t–1454t
efficiency and cost-effectiveness of, 1463–1464
evidence for efficacy of, 1439
factors affecting outcome, 1461–1463
future directions of, 1465–1466
individual treatment v., 1439–1442, 1440t–1441t
mindfulness-based, 1439, 1456, 1457t–1460t
practical issues in, 1464–1465
supportive/expressive, 1439
hypnosis for, 1434–1435
IASP classification of, 18–20, 19t, 20t
interdisciplinary management of, 1709–1716
cost-effectiveness of, 1710
empirical support for, 1709–1710
follow-up in, 1713–1714
future considerations for, 1715
history of, 1709
multidisciplinary approach v., 1709, 1710–1711

5543
 patient as active participant in, 1709
process of, 1713–1714
referral for, 1713
team composition and roles in, 1711–1713
theoretical basis for, 1710–1711
VA health system as model of, 1714–1715
intrathecal drug delivery for, 1640, 1640t
medical assessment in, 314–318, 314f
ancillary studies in, 317–318
location of pain, 316–317, 316f
pain history in, 317
physical examination om, 317
procedures for, 317–318
red flags in, 314–317
risk factors for delayed recovery, 317
motivation for behavioral change in, 1470–1479, 1728–1730
multidisciplinary assessment of, 313–327
nerve blocks for, 1607
operant conditioning and, 427
personality and, 318–319
plasticity in, 72, 72f
postsurgical, 843
predispositions in, 76–77
primary care management of, 1722–1731
assessment and evaluation in, 1726–1727
barriers to treating pain in, 1724–1726
challenges in, 1723–1724
model of, 1726–1730
new focus in, 1726
pain medicine training in, 1723, 1726
pharmacologic, 1727–1728
prognosis in, 17
psychiatric illnesses comorbid with, 430–452, 1410–1411 (See also
Psychiatric illness; specific illnesses)
psychiatric symptoms in, 432–433, 432f

5544
 psychogenic conceptualizations of, 82–83
psychological aspects of, 76–89, 318–323
assessment of, 318–323
as cause v. consequence, 318–319
as concomitants v. precursors, 319
problem areas to assess, 321–323
relaxation techniques in, 1406, 1407–1408
resilience in, 77
skepticism and disbelief about, 76
status quo v. search for new solutions for, 1722
stress and, 420–421
substance abuse history and treatment of, 1001–1011
assessment tools in, 1006–1007, 1006t
balance principle and, 1001
binary concept of pain and addiction in, 1003–1004
continuum of pain and addiction in, 1004, 1004f
detoxification in, 1005
opioid agonist treatment and, 1008–1009
opioids as “gold standard” and, 1010
opioids for analgesia v. opioid-stabilizing effect in, 1005–1006
patient triage in, 1008, 1008t
separating “motive” from “behavior” in, 1004–1005
societal issues in, 1009–1010
taper in, 1005
terminating opioid therapy in, 1005–1006
universal precautions in, 1007–1008, 1007t
“worst case scenario” approach in, 1009–1010
substance use disorder and management of, 465–466, 465t
suicide risk in, 467–469
Chronic Pain Grade, 17
Chronic pain management program, for spinal pain, 1306
Chronic pain psychoeducation, 1406–1407
Chronic Pain Self-Efficacy Scale (CPSS), 1305
Chronic pain syndrome, 155
Chronic paroxysmal hemicrania, 1027

5545
Chronic refractory angina pectoris, 1191
Chronic widespread pain (CWP), 13, 526–527
gender differences in, 91–92
genetics and, 96
Chronological makers, of pain, 11, 12f
Churg-Strauss syndrome. See Eosinophilic granulomatosis with
polyangiitis
Cidofovir, for herpes zoster, 378
CIH. See Complementary and integrative health
Ciliary ganglion, 111, 112f, 113f
Cimetidine, 1051, 1765
Cimetropium bromide, for noncardiac chest pain, 1052
Cinacalcet, for calciphylaxis, 550
Cinderella hypothesis, 508
Cingulate cortex, 62, 65, 66f, 67–68
anatomic regions of, 67, 68f
anterior, 66f, 67–68, 108
functional imaging of, 67
in nociceptive modulation, 55t, 56f, 57
opioid analgesics and, 1336–1337
in pain processing, 67–68, 68f
in pain–ANS interaction, 114
midcingulate, 66f, 67
posterior, 66f, 67
Cingulotomy, 1701–1703
anatomy and physiology in, 1701
indications for, 1701
outcomes of, 1702–1703, 1702t
technique of, 1701–1702, 1702f
CINV. See Chemotherapy-induced nausea and vomiting
CIPN. See Chemotherapy-induced peripheral neuropathy
Ciprofloxacin, for prostate pain syndrome, 1103
Cisplatin, neuronopathy associated with, 335
Citalopram
for children, 918

5546
 for depression, 439
for fibromyalgia, 535
for neuropathic pain, 1360t, 1361t, 1362
for tension-type headache, 1133
Civil litigation, over pain management, 193, 195–198
damage or injury in, 193
duty/breach of duty in, 193
Clasp knife phenomenon, 234
Classical conditioning, 82, 425, 425f
aversive, 427
for burn pain, 904–905
fear/avoidance in, 427–428, 427f
and pain, 427–428, 427f
Classical trigeminal neuralgia. See Trigeminal neuralgia (classical)
Classification. See Taxonomies of pain
Classification of Chronic Pain (IASP), 1265
Claudication
intermittent, 567–569, 567f
neurogenic, 568, 1290
in thoracic outlet syndrome, 576, 1176
Clavicle, 1150–1158, 1155f
Clavus durum (hard corn), 1225–1226
Clavus mollum (soft corn), 1226
Claw sign, in spinal MRI, 261, 261f, 262f
Claw toe deformity, 1225, 1226f
Clindamycin, for hidradenitis suppurativa, 555
Clinical gaze, 143
Clinical judgment, and end-of-life care, 161
Clinical pain pharmacist, 1712
Clinical pharmacology, 1311
Clinical trials, 123–135
adaptive designs in, 132
allocation concealment in, 126
alternative study designs in, 131
baseline similarity in, 127

5547
 Bayesian statistical inference in, 132
blinding in, 127
cluster, 131
comparative effectiveness in, 132
control groups in, 124–126
cost-effectiveness analysis in, 131
crossover, 131
efficacy v. effectiveness in, 130
enriched enrollment randomized withdrawal, 132
equal treatment except for variable in, 127–128
equivalence, 132
expertise-based, 132
factorial design in, 131
funding source effects in, 130
generalizability of results in, 130
harms assessment in, 130–131
intention-to-treat analysis in, 128
low loss to follow-up in, 128
new directions in, 131–132
noninferiority, 132
outcome measures in, 128–129, 128t
pragmatic, 131
quality of, evaluating, 127, 127t
randomized, 126
reducing bias in, 127–128, 128t
reporting results of, 129
statistical power in, 129
stepped wedge design in, 132
subgroup analyses in, 130
Clobetasol, for bullous pemphigoid, 558
Clodronate, for bone pain in cancer, 746
Clomipramine
for central pain, 400
for neuropathic pain, 400, 1359–1361, 1360t, 1361t
Clonazepam

5548
 for end-of-life pain, 1737
for fibromyalgia, 537
for noncardiac chest pain, 1054
for spinal cord injury, 589
for trigeminal neuralgia, 1114
Clonidine
for acute pain, 831, 834
for bone pain in cancer, 747
for burn pain, 902
for central pain, 403
for childbirth pain, epidural, 947t, 948
for complex regional pain syndrome, 353, 1626–1627
epidural, 1684
for children, 819, 819t
in intensive care unit, 1787
intrathecal, 714t, 715, 852, 1625t, 1626–1627
for neuropathic pain, 1375
for spinal cord injury pain, 592
trial of, 1631t
withdrawal in, 1639
for noncardiac chest pain, 1052–1053
for opioid withdrawal, 1764
perineural, 854
for phantom pain prevention, 364–365
for postherpetic neuralgia, 388
for residual limb pain, 368
with spinal cord stimulation, 1572
topical, 1684
for trigeminal neuralgia, 1115
Clonidine-induced growth hormone secretion, 435
Clorazepate, for spinal cord injury, 589
Closed kinetic chain, 1498t
Closed therapy groups, 1464
Close-ended questions, 1473t
Clostridium difficile, in HIV/AIDS, 986

5549
Clouser, K. Danner, 166
Cluster headache, 1025–1027, 1025t, 1134
acute attack treatment for, 1027
in children, 922–923
diagnostic criteria for, 1026t, 1134
differential diagnosis of, 1026, 1026t
epidemiology of, 1025
functional imaging in, 1020, 1021f
management of, 1026–1027, 1134
neuroimaging of, 268f
pathophysiology of, 1134
periodicity of, 1025
peripheral nerve stimulation for, 1565, 1566
preventive treatments for, 1026–1027, 1027t
surgical treatment for, 1027
trigeminal neuralgia v., 1112–1113
Cluster trials, 131
CMAP. See Compound motor action potential
CMV. See Cytomegalovirus
CNA. See Competent National Authority
CNS. See Central nervous system
Coagulopathy, neuraxial techniques contraindicated in, 853
Coating agents, for oral mucositis, 737, 740
Coblation, 1647
Cocaine, 8
as local anesthetic, 8, 1382, 1386t
synthetic analogues of, 1382
urine testing for, 1509t
Cocaine levamisole toxicity, 549, 549f
Coccygeus, in male pelvic pain, 1102
Coccyodynia, 1088
Cochrane Collaboration, 133
“Cocktail party” effect, 70
COCP. See Combined oral contraceptive pill
Codeine, 1334t, 1345

5550
 for burn pain, 903
for cancer pain, 695–696
for children, 812–813, 814t
dose conversions of, 829t
in emergency department, 1775
hepatic dysfunction and, 689t
in intensive care unit, 1787
metabolites of, 1347t
relative efficacy of, 829t
renal dysfunction and, 688t
for tension-type headache, 1133
urine testing for, 1016, 1016f, 1509t
Coding
CPT, 15
IASP, 19–20, 19t, 20t
Coenzyme Q10, for migraine prevention, 1023t
Coffee, for hypnic headache, 1028–1029
Cognition
assessment of, 227, 231
burn pain and, 903–904
as component of pain, 410
confusion techniques and, 1435
and consciousness, 1422
emotion and, 410, 417–418
opioid effects on, 697–698
and sense of self, 418
Cognitive appraisal, in anger, 1395
“Cognitive Behavioral Therapy for Chronic Pain Is Effective, But for
Whom?” (Broderick, Keefe, Schneider, et al.), 144
Cognitive distortions, 437–438, 1401, 1408–1409, 1409t
Cognitive experience, of pain, 225, 790–791
Cognitive factors, in pain, 76–79
Cognitive impairment, 231
Cognitive processing therapy, 444
Cognitive restructuring, 1401, 1406, 1408–1409

5551
Cognitive theory, of depression, 437–438, 440
Cognitive-behavioral affective therapy (CBAT), 1401
Cognitive-behavioral model, 83–85
Cognitive-behavioral theory, of depression, 438, 440
Cognitive-behavioral therapy (CBT), 85, 86, 428–429
for abdominal pain, 1070
for anger, 1401
for anxiety, 441, 442, 1417–1418
for back pain, 1272–1273, 1541
group, 1442, 1443t, 1445t, 1446t, 1449t–1452t, 1454t, 1461
for burn pain, 903–904
for cancer pain, 739
for cancer pain in children, 800
for children with sleep problems, 920
for chronic pain, 468–469, 1405–1413, 1417–1418
A-B-C model in, 1406–1407, 1407t
behavioral activation in, 1406, 1408
in children, 918–919, 923
components of, 1406–1412
evidence for, 1405–1406
group, 1439–1456
group v. individual, 1439–1442, 1440t–1441t
group v. wait-list, treatment as usual, or other group treatments,
1442–1456, 1443t–1454t
history and development of, 1405
Internet-delivered, 1442
in interprofessional pain programs, 1411
maintenance and relapse prevention in, 1406, 1409–1410
third-wave therapies in, 1405, 1410
treating comorbid conditions in, 1410–1411
for complex regional pain syndrome, 353–354
contextual, 1418
for anxiety and depression, 1418
group, for chronic pain, 1456–1461
for depression, 440, 1417–1418

5552
 developments in, 1418
for elderly patients, 934, 935
as essential component of pain management, 429
for failed back surgery, 1295
for fibromyalgia, 536t, 538
group
acceptance-based approaches v., 1461
advantages of, 1463–1464
compliance with homework and skills practice in, 1463
future directions of, 1465–1466
group processes in, 1463
importance of cognitive change in, 1461–1463
mindfulness-based approaches v., 1456
practical issues in, 1464–1465
tailored to symptom profiles, 1455–1456
therapist skill and time in, 1463
for HIV pain, 997
hypnosis v., 1425–1426, 1431
major components of, 428t
motivation enhancement therapy v., 1472, 1472t
for noncardiac chest pain, 1055
for posttraumatic stress syndrome, 444
for preventing acute-to-chronic pain transition, 1411–1412
for rehabilitation, 1411, 1494, 1496, 1497t, 1499–1500
for sleep disorders, 468–469
for spinal cord injury pain, 593
for substance use disorder, 469, 1512
for suicide risk, 468–469
Cognitive-behavioral therapy for insomnia (CBT-I), 920
Cognitive-evaluative system, 65, 83
Cognitively impaired persons, pain assessment in, 1734, 1734t, 1772
Cognitive-motivational-relational theory of emotion, 1395, 1395t
Coin technique, in hypnosis, 1432
Colchicine
for calcinosis cutis, 549

5553
 for calcium pyrophosphate deposition disease, 497
for epidermolysis bullosa, 558
for gout, 500, 1224
for leukocytoclastic vasculitis, 546
for relapsing polychondritis, 558
Cold, for neurolytic blockade, 1653, 1654–1655
Cold sensation, 398
Cold therapy (cryotherapy), 1523–1524
Colitis, in HIV/AIDS, 986
Collaborating Centre for Drug Statistics Methodology, 208
Collaborative care models, 1730
Colocalization, of neurotransmitters, 48
Colon
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Colon pain, in cancer, 652
Colorectal cancer, 642–643
depression in, 630
epidemiology of, 621, 622f, 642–643
pain in, tumor type and stage of disease in, 638
palliative radiation therapy for, 767
Columbia-Suicide Severity Rating Scale (C-SSRS), 468
Combat support hospital, 838
Combination NSAID medications, 1323–1324
Combined medial and lateral syndrome, 1170t
Combined oral contraceptive pill (COCP)
for dysmenorrhea, 1083–1084
for endometriosis, 1086t
Combined spinal-epidural (CSE) analgesia, 1385
for acute pain, 852
for childbirth pain, 946, 948–949
advantages and disadvantages of, 947t, 948
complications of, 949
drugs for initiating, 948–949, 948t
needle-through-needle technique for, 948

5554
 side effects of, 949
complications of, 852–853
contraindications to, 853
needle through needle technique of, 852
separate needles technique of, 852
COMFORT scale, 289, 790, 1783
COMM. See Current Opioid Misuse Measure
Commission on Accreditation in Physical Therapy Education (CAPTE),
1522
Commission on Accreditation of Rehabilitation Facilities (CARF), 1491,
1494, 1501, 1709, 1714
Common peroneal nerve entrapment, 267–268
Communication
in compliance monitoring, 1012–1013
in end-of-life care, 160, 162–163
4 E’s of, 480, 480t
in interdisciplinary management, 1710–1711
in nonverbal, cognitively impaired older adults, 930–931
in overt expressions of pain, 321–322
in patient encounters, 479–480, 479t, 480t
in pediatric pain management, 140
SPIKES protocol for, 162–163
Communication skills, in cognitive-behavioral therapy, 1406, 1409
Comparative effectiveness, 132
Compartment syndrome, chronic, 568–569
Competent National Authority (CNA), 207
Complementarity, 1422–1423
Complementary and alternative medicine, 1547, 1547t. See also
Complementary and integrative health
Complementary and integrative health (CIH), 145–146, 1546–1557
for abdominal pain, 1072
argument for using, 1549
biologically based, 1549, 1550–1555
for cancer pain, 701–702
for cancer pain in children, 799–802, 799t

5555
 categories of, 1549
for children with chronic pain, 919
definition of, 1546, 1547t
distinguishing features of, 1548
energy-based, 1549, 1552–1555
evidence-based, challenges of, 1549–1550
for fibromyalgia, 536t, 538
for herpes zoster, 379
historical perspective on, 1546–1547
in intensive care unit, 1787
for older persons, 934, 935
popularity with public, 1547
for posttraumatic stress disorder, 444
research on and quality of, 1547–1548, 1555, 1555t
Complementary medicine, 1547, 1547t. See also Complementary and
integrative health
Complete decongestive therapy, 1530
Complex regional pain syndrome (CRPS), 13, 341–362, 645t
afferent dysfunction in, 343
altered perception in, 229
animal models of, 341–342
Budapest criteria for, 347, 347t
central dysfunction in, 343
in children, 910, 921–922
clinical presentation of, 344
convergent pathophysiologic theory of, 345, 346f
desensitization for, 1529–1530
diagnosis of, 345–349
dorsal root ganglion stimulation for, 354–355, 1558, 1564
dystrophic abnormalities in, 344–345
electrodiagnostic tests in, 248, 249–250
epidemiology of, 341
functional restoration in, 349–350, 350f, 355
genetics of, 345
human models of, 342

5556
 hypnosis for, 1423–1424, 1428
IASP criteria for, 341, 341t, 346
immobilization and disuse in, 345, 349, 350
immunologic factors in, 342–343
inflammation in, 342
interdisciplinary approach in, 351, 355
interventional therapies for, 354–355
intrathecal drug delivery for, 1626–1627
manual lymphatic drainage for, 1530
motor and movement disorders in, 345
neuroimaging in, 343, 345
nutritional abnormalities in, 344–345
pain diagram in, 228f
pathophysiology of, 341–345
peripheral nerve stimulation for, 1564
pharmacotherapy for, 351–353, 352f
plasticity in, 72
psychological factors in, 348–349
psychological interventions for, 353–354
quality of pain in, 1160
rehabilitation-based modalities for, 350–351
sensory testing in, 1163
sequential stages and subsets of, 347–348
sympathectomy for, 354, 355, 1685
sympathetic dysfunction in, 343–344, 1685
sympathetic skin response in, 248
synonyms for, 341
thoracic outlet syndrome v., 578
treatment of, 349–355
trophic changes in, 233f, 344–345
type 1, 13
type 2, 13
Complex repetitive discharges, 247, 247f
Complex visceral pain syndromes, 756
Compliance, in group therapy, 1463

5557
Compliance expectations, 1009
Compliance monitoring, 1012–1017
communication and, 1012–1013
definition of, 1012
future considerations in, 1017
individual risk assessment in, 1012
interpreting aberrant behavior in, 1013–1014
pill loads
in avoiding excessive, 1013–1014
limits to modify behavior, 1014
potential treatment traps in, 1013–1014
terminating opioid therapy in, 1005–1006, 1017
tips and traps in, 1014
urine drug testing in, 1012, 1014–1017, 1015t, 1016f
worst-case scenario in, 1009–1010, 1012
Complications, 1758–1769. See also specific procedures and
complications
anaphylaxis, 1764–1765
bleeding, 1758–1760, 1760f
catastrophic neural injuries, 1765–1767, 1767f
infectious, 1760–1761
intrathecal drug delivery, 1764
malpractice claims over, 1758, 1758t, 1759f
pain clinic, 1758–1769
unintended destinations of local anesthetics, 1763
vasovagal reactions, 1763–1764
Compound motor action potential (CMAP), 244–245, 1673
Comprehensive Drug Abuse Prevention and Control Act of 1970, 176
Comprehensive Sickle Cell Centers, 970
Comprehensive systems approach, for opioid use, 176
Compression fractures, spinal, 1187, 1187f
diagnostic imaging of, 259–261
Computed tomography (CT), 251
in acute headache, 251–255, 1029
of aneurysm, 252f

5558
of arteriovenous malformation, 253f
in bone cancer, 745
in brainstem ablation, 1705
in celiac plexus neurolysis, 718
in central pain states, 396, 398
in chronic pain evaluation, 317
in cordotomy, 727
in diffuse idiopathic skeletal hyperostosis, 1188
in epidural steroid injections, 1611, 1612t, 1620
in failed back surgery, 1290–1292, 1294
in headache, 1021
in interdigital neuroma, 1224
in internal disk disruption, 1645, 1645f
intraoperative, 268
in Lisfranc joint instability, 1221
in low back pain, 1252–1253, 1252t
in lumbosacral plexopathy, 1205
in metastatic spinal cord compression, 772, 773f
in myelotomy, 728
in neck and arm pain, 1168
in nerve block guidance, 1597, 1598f
in pathologic fracture, 771
in percutaneous cordotomy, 1700
of peripheral nerve entrapment, 267
in peripheral nerve stimulation workup, 1563
in sesamoiditis, 1223
of spine (spinal pain), 258–261
compression fracture, 259
in spine surgery evaluation, 1289
of subarachnoid hemorrhage, 251, 252f, 253f, 254–255
in temporomandibular joint disorders, 1132
in thalamotomy, 1703
in thoracic outlet syndrome, 577–578
in trigeminal neuralgia, 1112
in venous sinus thrombosis, 254f, 255f

5559
 of vertebral fracture, 1187, 1187f
Computed tomography angiography (CTA)
of arterial dissection, 255f
of arteriovenous malformation, 253f
of subarachnoid hemorrhage, 251, 253f, 255–256, 255f
of thoracic outlet syndrome, 577, 577f, 1176
Computed tomography myelography, 258, 586–587, 1030
Computer adaptive testing, 227
Computer reality. See Virtual reality
COMT gene, 96, 97
Concentric electromyography, 247, 247f
Concentric exercise, 1497–1498, 1498t
Conditioning
for burn pain, 904–905
classical, 82, 425, 425f
aversive, 427
for burn pain, 904–905
fear/avoidance in, 427–428, 427f
and pain, 427–428, 427f
cognitive-behavioral model and, 83–84
operant, 82–83, 425–426, 904–905
and chronic pain, 427
in depression, 437
for low back pain, 1541
and pain, 426–427
in pain treatment outcome, 445
for substance use disorder, 1513
Confounding, 125–126
Confusion techniques, 1435
Conjunctivitis, in reactive arthritis, 495
Connective tissue disorders, 558–559
Consciousness, 143–144, 147, 1422–1423
content of, 1422
hypnosis and, 1422–1423
reticular formation and, 63

5560
 selective, 1422
thalamus and, 65
Consciousness raising, 1472t
Consent, informed
in end-of-life care, 160
in pain medicine, 1007
Conservative care gatekeepers, 1718
Constant flow infusion pumps, 1632, 1632t
Constipation
blocking afferent pathways in, 1070
opioid-induced, 682–683, 697t, 1341
in children, 798–799, 816–817, 817t
in elderly patients, 933
μ-opioid receptors in, 1333–1336
tolerance to, 1338–1339
treatment of, 683, 1341
pelvic pain in, 1088
Constitutional cases, over pain management, 201–202
Construct validity, 272
Consultations, history of, 232
Consumption data, on opioid analgesics, 207–215
disparities, 207–209, 208t
trends, 208–215, 209f, 211f–214f
Contact point headache, 1135
Content validity, 272
Contextual cognitive-behavioral therapy (CCBT), 1418
for anxiety and depression, 1418
group, for chronic pain, 1456–1461
Contextual model. See Biopsychosocial model
Contingency management, 1513
Continuous epidural analgesia
for acute pain, 833–836, 833t, 850–851
for childbirth pain, 947t, 949
Continuous labor support, 945
Continuous opioid infusions, for children, 815

5561
Continuous peripheral nerve blockade (CPNB), 856–857
Continuous spinal analgesia, for childbirth pain, 947t, 949
Contracts, opioid, 156–157, 617, 1007, 1008t
Control, perceived, 78–79, 142
Control groups, 124–126
matching of, 125–126, 125t, 128t
placebo in, 124–125
randomized allocation of treatment and, 126
waiting list, 125, 126
Control points, in fibromyalgia, 526
Controlled substances, 173–174, 206. See also Law and policies, affecting
pain management
Controlled Substances Act (CSA), 176–180
classification schedules under, 176
criminal litigation over, 198, 199–201
enforcement of, 176–177
medical availability under, 177
medical practice not regulated under, 177–178
prescription amount or duration not limited under, 179
prescription requirements under, 177
secure disposal under, 179–180
treatment of addiction v. treatment of pain under, 178–179
Controlled-release opioids, 1342
Conundrums, in pain assessment, 313
Convention on Psychotropic Substances of 1971, 178
Conventional medicine
complementary and integrative health v., 1546–1548
definition of, 1547t
utilization of, 1548–1549
Convergent neurons, 42–43
Conversion, 1392–1393
Conversion disorder, 299, 446, 447, 447t
Conversion-V profile, 1393
Convincers, in hypnosis, 1433
Cool and noxious cold, 235

5562
COPCs. See Chronic overlapping pain conditions
Coping, 79, 84
assessment of, 230, 322–323, 1302, 1303t
burn pain and, 903–904
in children, 912, 915
definition of, 1302
ethnic differences in, 95–96
gender differences in, 94
group therapy and, 1461–1463
in noncardiac chest pain, 1055
positive strategies of, 230
in spine surgery candidates, 1302, 1303t
styles of, 903–904, 904f
Coping planning, 1476
Coping Strategies Questionnaire (CSQ), 320, 1302, 1305
Coracoacromial ligament, 1157, 1157f
Coracoclavicular ligament, 1150, 1156, 1157f
Coracohumeral ligament, 1157, 1157f
Cordomyelotomy, 594
Cordotomy, 594, 1700–1701
anatomy and physiology in, 1700
for cancer pain, 727–728
complications of, 728
indications for, 727, 1700
open thoracic, 1701
outcomes of, 728, 1701
percutaneous, 1657, 1700
technique of, 727–728, 727f, 1700–1701
Core stability, 1486–1487, 1498t
Core values, of health care, 151–152
Corn
hard, 1225–1226
soft, 1226
Cornu ammonis, 70
Coronary artery disease

5563
 costochondritis v., 1189
in HIV/AIDS, 987
noncardiac chest pain in, 1034
Cortex (cerebral cortex), 65–70
Brodmann classification of, 65
functional areas of, 65
integrative function of, 114
multidimensionality of pain and, 65
in pain–ANS interaction, 114
schematic anatomic localization of areas, 66f
sensory areas of, 55t, 66–67, 66f, 108
structures in nociceptive modulation, 55, 55t, 57
Cortical reorganization, 1497
Corticosteroids
for acute chest syndrome, 965–966
for acute pain, 831
as adjuvant analgesics, 685
for anaphylaxis, 1765
for ANCA vasculitis, 547
for ankylosing spondylitis, 1188
for antiphospholipid syndrome, 548
for bone pain in cancer, 746
for bullous pemphigoid, 558
for calcium pyrophosphate deposition disease, 497
for cancer pain, 685, 686, 757
and chemotherapy-related pain, 635
for cluster headache prevention, 1026, 1027t
for complex regional pain syndrome, 352
for costochondritis, 1189
for Dercum disease (adiposis dolorosa), 554
for discogenic pain, 1274
embolism of, 1765
for epidermolysis bullosa, 558
epidural injections of (See Epidural steroid injections)
for epidural spinal cord compression, 1183

5564
 for erythema nodosum, 554
for giant cell arteritis, 502, 1031
for gout, 500, 1224
for herpes zoster, 378, 1118
for intercostal neuralgia, 1186
intralesional injections, for bone pain, 747–748
for leukocytoclastic vasculitis, 546
for manubriosternal arthritis, 1190
neural injuries from injection, 1765–1767, 1767f
for osteoarthritis, 490
for pemphigus vulgaris, 557
perineal pain with, 756
for polyarteritis nodosa, 547
for polymyalgia rheumatica, 502
for postherpetic neuralgia prevention, 390
for psoriatic arthritis, 496
for pyoderma gangrenosum, 552
for reactive arthritis, 495–496
for relapsing polychondritis, 558
for rheumatoid arthritis, 493
for sacroiliac joint pain, 1276–1277
for spinal cord injury pain, 588
for sternoclavicular joint arthritis, 1189
for Stevens-Johnson/TEN syndrome, 557
for thoracic facet syndrome, 1188
for xiphoidalgia, 1190
for zygapophysial joint pain, 1274
Corticotropin-releasing hormone (CRH), 419
Cortisol
in anger (negative emotions), 1394
in fibromyalgia, 531
in stress response, 79
Cost
of intrathecal drug delivery, 713, 713t, 1630
of opioid analgesics, 218–219

5565
 of radiation therapy, 765
Costal cartilage, chest wall pain from disorders of, 1189, 1198t
Cost–benefit analysis, 13
Cost-effectiveness analysis, 13, 131
Costochondral dislocation, 1189, 1198t
Costochondritis, 1189, 1198t
Costoclavicular joint, 1150
Costoclavicular ligament, 1150
Costopleural syndrome, 1184, 1184f
Costovertebral arthritis, 1188, 1198t
Costs, pain-associated, 172
Cough, opioid analgesics and, 1338
Cough headache, primary, 1028
Coumadin. See Warfarin
Council of Europe, 174
Counterconditioning, 1472, 1472t
Counterirritants, topical, 1356–1357
Counterirritation, 63
Course of professional practice, 178
COX-1. See Cyclooxygenase-1
COX-2. See Cyclooxygenase-2
CPNB. See Continuous peripheral nerve blockade
CPOT. See Critical-Care Pain Observation Tool
CPPD. See Calcium pyrophosphate deposition disease
CPSP. See Central poststroke pain
CPSS. See Chronic Pain Self-Efficacy Scale
CPT (current procedural terminology), 15
Crandall and Batzdorf classification, of cervical spondylotic myelopathy,
1170, 1170t
Cranial nerves, 103, 1162, 1162t
cancer-related pathology in, 653–657
nerve conduction studies of, 246
Cranial neuralgias, 1108–1127. See also specific neuralgias
atypical, 1108, 1108t
cancer-related, 653–657

5566
 definition of, 1108
facial pain syndromes in, 1108, 1108t
nomenclature and classification of, 1108
rare presentations of, 1122–1123
secondary, 1108
typical, 1108, 1108t
Cranial pain, dorsal rhizotomy or ganglionectomy for, 1680
Cranial parasympathetics, 111, 112f
Craniosacral therapy (CST), 1553–1554
Crawford Small Parts Dexterity Test, 1502
C-reactive protein (CRP), 962, 1168, 1252, 1252t
Creatinine phosphokinase, 962
CRF. See Cancer-related fatigue
Cricoid cartilage, 1139f
CRIES scale, 810
Crile, George, 442
Criminal litigation, over pain management, 198–201
Crisis intervention, for PTSD, 444
Criterion validity, 273
Critical illness. See also Intensive care unit
pain and analgesia in, 1782–1783
Critical-Care Pain Observation Tool (CPOT), 1784–1785, 1784t
Crohn’s disease, arthritis associated with, 496–497
Cromwell, Florence, 1491
Cross-cultural studies, 141–143
Crossover trials, 131
Cross-tolerance, 691, 1339–1340, 1527
CRP. See C-reactive protein
CRPS. See Complex regional pain syndrome
Cruikshank, George, 138, 138f
Cruzan, Nancy, 163
Cryoneurotomy, 1653, 1654–1655
Cryotherapy
in oral mucositis prevention, 737, 740, 796
in physical therapy, 1523–1524

5567
Cryptococcus, in HIV/AIDS, 992
Cryptosporidium, in HIV/AIDS, 986
Crystal arthritis, 484, 497–500. See also Gout
CSA. See Controlled Substances Act
CSE. See Combined spinal-epidural (CSE) analgesia
CSHQ. See Children’s Sleep Habits Questionnaire
CSM. See Cervical spondylotic myelopathy
CSQ. See Coping Strategies Questionnaire
C-SSRS. See Columbia-Suicide Severity Rating Scale
CST. See Craniosacral therapy
CT. See Computed tomography
CTA. See Computed tomography angiography
CTS. See Carpal tunnel syndrome
Cubital tunnel syndrome (CuTS), 1173, 1175
“Culpability of cultivated ignorance,” 153
Cultural Ontology of the Self in Pain (George and Jung, eds.), 141
Culture. See also Sociocultural perspective
and anger, 1392
beliefs, attitudes, perceptions, and behaviors in, 141–143
and cancer pain, 600
importance of addressing, 296
The Culture of Pain (Morris), 151
Cupping, 1, 1530–1531
Curative care
palliative paradigm v., 152, 152t
transition to palliative care, 160–163
Curcumin, for abdominal pain, 1072
Current medications, 232
Current Opioid Misuse Measure (COMM), 227, 231, 465, 700
Current procedural terminology (CPT), 15
Cutaneous analgesia, for children, 817
Cutaneous endometriosis, 560
Cutaneous fields, of peripheral nerves, 105f
Cutaneous neurovascular disease, 559–560
Cutaneous sensory nervous system, 543

5568
Cutaneous ulcers, 550–551
ischemic (arterial), 550
pyoderma gangrenosum, 551–552, 551f
venous, 550–551, 551f
Cutaneous vascular disorders, 546–550. See also Cutaneous vasculitis
Cutaneous vasculitis, 543, 544t–545t, 546–548
eosinophilic granulomatosis with polyangiitis, 545t, 547
granulomatosis with polyangiitis, 544t, 547
leukocytoclastic, 546, 546f
livedoid, 545t, 548, 548f
microscopic polyangiitis, 545t, 547
polyarteritis nodosa, 544t, 546–547
rheumatoid, 545t, 547–548
CuTS. See Cubital tunnel syndrome
CWP. See Chronic widespread pain
CyberKnife surgery, for trigeminal neuralgia, 1116
Cyclic guanosine monophosphate (cGMP), 1070
Cyclobenzaprine, 1352t, 1354–1355
as adjuvant analgesic, 685
for fibromyalgia, 535, 536t
for low back pain, 1254
Cyclooxygenase-1 (COX-1), 1315–1317, 1317f, 1324f
Cyclooxygenase-1 (COX-1) selective NSAIDs
for acute pain, 829–830
for cancer pain, 681
for children, 810, 811
Cyclooxygenase-2 (COX-2), 1315–1317, 1317f, 1324f
Cyclooxygenase-2 (COX-2) inhibitors, for bone pain in cancer, 746
Cyclooxygenase-2 (COX-2) selective NSAIDs, 1316t, 1322–1323
for acute pain, 829–830
agents withdrawn from market, 1315, 1318, 1323, 1324
for cancer pain, 681
cardiovascular effects of, 1324–1326
for children, 810, 811, 917
for complex regional pain syndrome, 352

5569
 for elderly patients, 932
for endometriosis, 1087
gastrointestinal toxicity of, 1327
hematologic effects of, 1327
for hemicrania continua, 1029
for osteoarthritis, 490, 1322
for war trauma, 838
Cyclophosphamide
for ANCA vasculitis, 547
for pemphigus vulgaris, 557
for polyarteritis nodosa, 547
for relapsing polychondritis, 558
Cyclosporine
for leukocytoclastic vasculitis, 546
for psoriatic arthritis, 496
for pyoderma gangrenosum, 552
for relapsing polychondritis, 558
Cyriax, James, 504
Cystic fibrosis, chronic pain in, 911
Cystitis
interstitial, pelvic pain in, 1088–1089
radiation, 757
Cytokines, 49
in cancer pain, 627, 732
in depression–pain association, 436
in fibromyalgia, 531
in myofascial pain (trigger points), 512–513
in opioid-induced hyperalgesia, 457–458, 458f
in oral mucositis prevention, 738–739
in stress, 419–420
Cytomegalovirus (CMV)
in cancer treatment, 738
in HIV/AIDS, 986, 988–989, 992

D
Da Costa syndrome, 1191

5570
Dactylitis, 493, 494f, 968
Damage, in civil litigation, 193
Dämmerschlaf (twilight sleep), 940
Danazol, 548, 1086t, 1087
Dance/movement therapy, 800–801
Dantrolene, 589, 685
Dapsone, 546, 558
Darwin, Charles, 411
DAST. See Drug Abuse Screening Test
DBS. See Deep brain stimulation
DDPRQ. See Difficult Doctor–Patient relationship Questionnaire
DEA. See Drug Enforcement Administration
Deafferentation trigeminal neuralgia, 13, 1123, 1129
Death, malpractice claims over, 1758, 1759f
Death with Dignity Act (Oregon), 156, 168, 169, 202
Decisional balance, in behavior change, 1471–1473, 1473t
Decisional capacity, 163
Decision-making, in end-of-life care, 160–162
communication in, 160, 162–163
consideration of medical and nonmedical factors in, 160
departures from ideal, 161–162
honesty v. hope in, 162
ideal, 160
joint participation in (doctor–patient), 160
patient attitudes and values in, 161
physician attitudes and values in, 161–162
prognosis and clinical judgment in, 161
surrogate, 163–165
Deconditioning
in cancer pain, 615
in failed back surgery, 1292, 1294
Deep brain stimulation (DBS), 63, 1587–1589
basic considerations in, 1587
for central pain, 404
efficacy of, 1587–1588

5571
of PAG, 64, 1587–1589

5572
 for phantom pain, 367
for postherpetic neuralgia, 389
for spinal cord injury, 593
surgical technique for, 1588–1589, 1588f, 1589f
of VPL nucleus, 65, 1587–1589
Deep pain, 285
Deep peroneal nerve, 882
Deep second-degree burns, 897, 898f
Deep sedation, 900, 912t, 1777
Deep venous thrombosis (DVT), 570, 756
Defense and Veterans Pain Rating Scale (DVPRS), 289
Definitive urine drug testing, 1015–1016
Delayed recovery, risk factors for, 317
Delirium
in cancer patients, 616–617
postoperative, in elderly, 839–840
δ-Opioid receptor (DOR), 48, 1333
Dementia, pain assessment in persons with, 1734, 1734t, 1772
Demoralization Scale (DS), 631t
Demoralization Scale II (DS-II), 631t
Demyelinating neuropathies, 330
autoimmune, 333–334
in HIV/AIDS, 988–989
Denis classification, of sacral fractures, 650, 651f
Denosumab, for bone pain in cancer, 746, 794
Dens (odontoid process), 1138, 1139f, 1140f, 1142f
Dental caries, 1130–1131, 1130f
Dental (odontogenic) pain, 1130–1131
diagnosis of, 1130, 1131t
trigeminal neuralgia v., 1113
Dental radiographs, 1131, 1131f
Dentate gyrus, 70
Dentate ligament, 40f
Dentin sensitivity, 1131t
Dentistry, hypnosis in, 1429

5573
Department of Health Policy and Management, 172
Dependence, 178–179, 184, 454–457, 799, 1001–1002. See also Substance
use disorder
addiction v., 1001, 1002
assessment for, 231–232, 1508–1511
fear of, as barrier to use, 216
opioid, 456–457, 1001, 1338, 1340
assessment for, 231–232
neonatal, 1341
in rehabilitation, managing, 1503–1504, 1504t
spectrum of, 231
Dependence syndrome, 178–179
Depot medroxyprogesterone acetate (DMPA), for dysmenorrhea, 1084
Depression, 79–81, 433–440
anthropologic theories of, 438
anxiety disorders with, 440–441
assessment for, 227, 229–230, 237, 298, 322
behavioral approach for, 440, 1416
behavioral (operant conditioning) theory of, 437
biologic tests for, 435
in burn injury, 899
in cancer patients, 629–631
chemotherapy and, 630
detecting and assessing, 630–631, 631t
screening for, 631
as cause v. result of chronic pain, 80
chest pain in, 1202t
in chronic pain, 1414–1420
biogenic amines, cytokines, and neural pathways in, 436
biologic theories of, 435–436
in children, 912, 913, 914–915
cognitive-behavioral therapy for, 1410–1411
cortical substrates in, 436, 436f
endogenous v. reactive, 434
impact on functioning, 1414–1415

5574
 interaction of anxiety, depression, and chronic pain, 1415
mechanisms of association, 435–438
prevalence of, 1414
cognitive theory of, 437–438, 440
cognitive-behavioral theory of, 438, 440
cognitive-behavioral therapy for, 440, 1417–1418
in complex regional pain syndrome, 348–349
depressed mood v. major depression, 433
diathesis-stress model of, 438
differential diagnosis of, 434
in difficult patients, 476–477
double, 435
DSM criteria for, 433, 433t, 630
epidemiology of, 435
in failed back syndrome, 1292–1293, 1295
female pelvic pain in, 1084–1085
in fibromyalgia, 525–526, 530, 1415
in low back pain, 1251
male pelvic pain in, 1103
masked, 81, 437
mediating factors in pain, 81
in neck and arm pain, 1161
noncardiac chest pain in, 1041, 1050, 1055
pharmacotherapy for, 438–439, 1416–1417
primary care and, 1725
psychological theories of, 437–438
psychotherapy for, 439–440
sickness response and, 420
sleep disturbance in, 437
in somatization, 1300–1301
in spine surgery, 1299–1300, 1304
suicidal ideation in, 433–434
treatment of, 438–440
Depression–pain dyad, 1410
Depressive spectrum disorder, 437

5575
Dercum disease, 554, 1190, 1200t
Dermatologic disorders. See also Skin
diagnosis of, 543–546
epidemiology of, 543
pain in, 543–565
Dermatomes, 103, 104f, 1145, 1147f, 1150f
arm/neck pain and, 1160
cancer pain and, 602, 612
childbirth pain and, 940–941
herpes zoster distribution and, 372–373, 374f, 374t, 1186
spinal cord injury pain and, 585
Dermatomyositis, chest pain in, 1199t
Dermis, 543
Descartes, René, 2–3, 3f, 313, 410–411, 1492, 1492t
Descending modulation, 53–57, 56f, 108–109
depression–pain association in, 436
facilitatory, 54
opioid-induced hyperalgesia and, 457
periaqueductal gray in, 54–56, 56f, 63–64
supraspinal substrates mediating, 54–57
tonic, 53–54, 54f
Descending tracts, 39, 40f, 108–109
Desensitization therapy, 368, 444, 1529–1530
Desflurane, for burn pain, 903
Desipramine
for acute pain, 832
for central pain, 400
for herpes zoster, 378
for neuropathic pain, 400, 1359–1361, 1360t, 1361t
for postherpetic neuralgia, 384t, 386
Desktop ergonomics, 1498, 1499t
Desmin, 506–507, 507f
Desvenlafaxine
for depression, 438–439
for neuropathic pain, 1360t, 1361–1362

5576
Detection times, in urine drug testing, 1015t, 1016, 1509, 1509t
Detoxification, 142, 178, 1005, 1340, 1511
Developmental disabilities, pain management for children with, 822
Devil’s grip, 1190
Dexamethasone
for acute pain, 831
for cancer pain, 685, 686
epidural injections of, 1611
perineural, 854
Dexamethasone-suppression test, 435
Dexmedetomidine
for acute pain, 831
for bone pain in cancer, 747
for burn pain, 902
intrathecal, 1626, 1627
perineural, 854
Dextromethorphan
for complex regional pain syndrome, 353
for neuropathic pain, 1367, 1368t
for phantom pain, 366
for postherpetic neuralgia, 388
Dextrose, hypertonic intradiscal, 1649
Dezocine, avoidance in cancer pain, 696
Diabetes mellitus
arthritis in, 489
foot lesions in, 569–570
low back pain in, 1251
nerve entrapment in, 1672
Diabetic amyotrophy, 335, 1207–1208
Diabetic lumbosacral radiculoplexus, 1207–1208
Diabetic mononeuropathies, 335
Diabetic neuropathy, 331, 1672
adjuvant analgesics for, 685
infrared therapy for, 1525
ocular, 1113

5577
 treatment of, 336
Diagnostic and Statistical Manual of Mental Disorders (DSM), 430–432,
432f, 432t
conversion disorder in, 447, 447t
generalized anxiety disorder in, 441, 441t
hypochondriasis in, 447–448, 448t
illness anxiety disorder in, 447–448
major depressive in, 433, 433t, 630
panic disorder/attack in, 441, 441t
personality disorders in, 444
posttraumatic stress disorder in, 443t
somatic symptom disorder in, 446–447, 446t
substance use disorder in, 178, 1508, 1773
Diagnostic Criteria for Psychosomatic Research (DCPR), 631t
Diagnostic imaging of pain, 251–271. See also specific imaging modalities
facial, 258
future applications of, 268
headache, 251–258, 1021
acute (subarachnoid hemorrhage), 251–256
chronic, 256–257
with intracranial hypertension, 258
with intracranial hypotension, 257–258
limb, 262–267
low back, 1252–1253, 1252t
spinal, 258–261
Diagnostic intra-articular blocks, 1605–1606, 1606f
Diagnostic nerve blocks, 1600–1605
applications of, 1602–1605
controls for, 1601
criteria for positive response in, 1601–1602
principles of, 1601–1602
rationale for, 1600
Dialectical behavior therapy, 1410
Dialysis, and opioid therapy, 687–688, 688t
Diaphragm, chest pain from disorders of, 1196t

5578
Diaphragmatic breathing, 1407
Diaphragmatic flutter, 1196t
Diaphragmatic pleuritis, 1196t
Diaphragmatic spasm, 1196t
Diaphragmatitis, 1196t
Diary
migraine, 1021, 1023
pain, 274–276, 286, 321, 916
Diathesis-stress model, 438, 444–445, 1415
Diazepam
for baclofen withdrawal, 1764
for end-of-life pain, 1737
for low back pain, 1254
for muscle spasm, 1352, 1352t, 1354, 1355
for spinal cord injury, 589
DIC. See Disseminated intravascular coagulation
Dickinson, Emily, 172
Diclofenac, 1316t, 1321
as adjuvant analgesic, 685
cardiovascular effects of, 1325
hematologic effects of, 1327
for HIV pain, 993, 994t
injectable, 1318, 1321
relative efficacy of, 829t
topical, 1318, 1319t, 1321
Diclofenac/misoprostol, 1324
Dicloxacillin, for cellulitis, 553
Didanosine, neuropathy associated with, 331
Diencephalon, 55t, 62, 62f
Dietary changes, for abdominal pain, 1068
Diethylstilbestrol, for priapism, 969
Differential blockade, 1384–1385
Difficult Doctor–Patient Relationship Questionnaire (DDPRQ), 476
Difficult doctor–patient relationships, 476–483
clinical scenarios of, 480–482

5579
 communication in, 479–480, 479t, 480t
health care system factors in, 476, 478
patient factors in, 476–478
patient interaction strategies in, 478–479
physician factors in, 476, 478
Difficult patients, 476–478
comorbid medical conditions in, 477–478
interaction strategies for, 478–479
“normal,” 477
opioid therapy in, 477
psychiatric and personality issues in, 476–477
Diffuse esophageal spasm (DES), 1038, 1038f
Diffuse hyperalgesia, 525, 529
Diffuse idiopathic skeletal hyperostosis (DISH), 1160, 1172, 1188, 1198t
Diffuse musculoskeletal pain, 921
Diffuse noxious inhibitory controls (DNIC), 43, 53, 78
Diffusion-weighted imaging, of spine, 261, 261f
Diflunisal, 1316t, 1320
Digital subtraction angiography, of subarachnoid hemorrhage, 255, 256
Dihydrocodeine, for neuropathic pain, 1366–1367, 1366t
Dihydroergotamine, for migraine, 989, 991t, 1024t, 1025
DiLeo, Lucas, 194
Diltiazem
for abdominal pain (IBS), 1071
for calcinosis cutis, 549
for noncardiac chest pain, 1052
for primary sex headache, 1028
“Dilute and shoot” approach, 1017
Dimensions, in psychiatric illness, 431
Dimethyl sulfoxide (DMSO), 1649
Diphenhydramine
for anaphylaxis, 1765
for nausea/vomiting in cancer patients, 684t
for oral mucositis, 737
for priapism, 969

5580
Dipyridamole, for livedoid vasculitis, 548
Direct immunofluorescence assay, in herpes zoster, 374
Directional preference exercise, 1540, 1542
Disability, 302–303
association with impairment, 303
biopsychosocial model of, 1492–1493, 1492f, 1493f
chronic pain in children and, 911–912
culture and beliefs about, 142
definition of, 13, 302, 1537
domains of limitations in, 303
fibromyalgia and, 539
low back pain and, 1537
pain rehabilitation and, 1492
short-term v. long-term, 303
social status of, 303
vocational, 231
Disability evaluation, 302–312
agencies involved in, 302
AMA guide for, 311
basic concepts in, 302
conceptual and empirical issues in, 302–304
pain in
“embeddedness” problem with, 303–304
methods for evaluating, 304–311
practical problems in identifying role of, 304
Social Security Administration, 302, 304–307, 305f
unbearable sensations in, 302
Washington State DLI, 302, 307–311
Disability insurance, 146
Disability-adjusted life years (DALYs), 1158
Disc degeneration, diagnostic imaging in, 258–261
Disc replacement, 1283–1286
Disciplinary actions, over pain management, 193–195
Discitis, MRI of, 261, 261f, 262f
Discogenic pain, 1265, 1274, 1643. See also Low back pain

5581
 in cervicogenic headache, 1171
diagnostic imaging in, 261, 263f–264f
discography and fusion for, 1284, 1284t
disk stimulation for, 1234, 1267–1268, 1643
epidural steroid injections for, 1274, 1648–1649
in failed back surgery, 1290, 1290t, 1291, 1291t, 1295
intradiscal therapies for, 1274, 1278, 1643–1652
magnetic resonance imaging in, 1278
Modic lesions and, 1645, 1646f, 1647t, 1648–1649
prevalence of, 1234–1235, 1645
sinuvertebral nerve blocks for, 1268
Discography, 261, 263f–264f, 1283–1284, 1284t, 1643
CT, of internal disk disruption, 1645, 1645f
Discrete nerve syndrome, 1671
Discriminative stimulus, 426
Disease conviction, 447
Disease perspective, on psychiatric illness, 431
Disease-modifying antirheumatic drugs (DMARDs), 491–493, 492t
for ankylosing spondylitis, 494
biologic, 492–493
early initiation of, 491–492
DISH. See Diffuse idiopathic skeletal hyperostosis
Disinhibition hypotheses, of central pain, 399–400
Disk(s)
cervical, 1138–1139, 1139f
cervical v. lumbar, 1140t, 1141f
hydraulic mechanism of, 1139, 1140f
Disk ablation, 1646–1647
Disk disruption, internal, 1644–1645, 1645f
Disk herniation
epidural steroid injections for, 1611
in failed back surgery, 1290, 1290t, 1291
surgery for, 1298
thoracic, chest wall pain in, 1184, 1185f
Disk pathology, 315, 1139, 1168–1170, 1643–1645, 1644f, 1645f

5582
Disk stimulation, 1643
cervical, 1234, 1234f, 1237, 1237f
lumbar, 1267–1268, 1267f
Disk stress profile, 1644, 1644f
Disposal, of controlled substances, 179–180, 187
Dissecting aneurysm, thoracic aorta, 1193t
Disseminated intravascular coagulation (DIC), 853
Dissociation, in hypnosis, 1423
Distal acquired demyelinating syndrome (DADS), 333
Distal symmetric polyneuropathy (DSP), 331–333, 988, 997
Distorted thinking, 84
Distraction, 904, 905–906, 906f, 1435
Distraction test, 1165–1166
Distribution (pharmacokinetics)
end-of-life organ dysfunction and, 1736
of intrathecal drugs, 1623, 1623f
of local anesthetics, 1384
of NSAIDs, 1318
Distribution system, for opioid analgesics, 217–218, 218f
Disulfiram, 1513
Disuse, in complex regional pain syndrome, 345, 349
Ditan, for migraine, 1024
Diversion
definition of, 1002t
at end of life, 619
and pain policy, 186–187
DLFs. See Dorsolateral funiculi
DLPFC. See Dorsolateral prefrontal cortex
DLPT. See Dorsal lateral pontine tegmentum
DMARDs. See Disease-modifying antirheumatic drugs
DMI. See Drug Misuse Index
DMPA. See Depot medroxyprogesterone acetate
DN4. See Neuropathic Pain Diagnostic Questionnaire
DNB. See Dorsal noradrenergic bundle
DNIC. See Diffuse noxious inhibitory controls

5583
Doctor–patient relationship. See Physician–patient relationship
Docusate, 798–799
Dolasetron, for nausea/vomiting in cancer patients, 684
DOLOPLUS 2, 289
Domperidone, for migraine, 1024, 1024t
Dopamine, 46t, 49
in addiction, 1002–1003, 1003f
in anger (negative emotions), 1394
in brainstem, 63, 64
in emotion, 414
in fibromyalgia, 530
mesolimbic system of, 64
opioid analgesics and, 1336–1337
in vigilance network, 70
DOR. See δ-Opioid receptor
Dorsal column neurons, postsynaptic, 45
Dorsal foot ganglia, 1221–1222
Dorsal horn, of the spinal cord, 39, 41f, 107
Dorsal lateral pontine tegmentum (DLPT), 827
Dorsal myelotomy, for cancer pain, 760
Dorsal noradrenergic bundle (DNB), 414–415, 414f
Dorsal reticular nucleus (DRt), 55t
Dorsal rhizotomy, 1668, 1678–1682, 1679f
basic considerations in, 1678–1679
clinical considerations in, 1679–1680
indications and outcomes, 1680–1682
operative technique of, 1680
preoperative evaluation for, 1679–1680
Dorsal root entry zone (DREZ) lesioning, 399, 594, 1657, 1698–1700
anatomy and physiology in, 1698–1699
for cancer pain, 729
indications for, 1698
outcomes of, 1699–1700
technique of, 1699, 1699f
Dorsal root ganglia (DRG), 103, 106, 114, 628, 745, 1144f

5584
Dorsal root ganglia blocks, for postherpetic neuralgia, 389
Dorsal root ganglion stimulation (DRGS), 1558
for axial back pain, 1564
for complex regional pain syndrome, 354–355, 1558, 1564
complications of, 1566–1567
future directions in, 1567
for groin neuralgia, 1565
implantation techniques for, 1561f, 1563
indications for, 1563t, 1564
pathophysiology and mechanisms of, 1559
for phantom pain, 367
for postherpetic neuralgia, 389, 1565
technology for, 1559–1560, 1560f
Dorsal scapular nerve, 1153t
Dorsolateral funiculi (DLFs), 55, 56
Dorsolateral pathways, of axonal projections, 44
Dorsolateral prefrontal cortex (DLPFC), 68–70, 69f
in depression–pain association, 436, 436f
Doshas, 1552
Dosulepin, for migraine prevention, 1023t
Double depression, 435
Double effect, rule of, 168–169
Double-blind trials, 127
Double-crush syndrome, 576
Douleur Neuropathique en 4 Questions (DN4), 396
Doxycycline, for hidradenitis suppurativa, 555
Drainage procedures, in cancer, 679
Drama therapy, 800–801
Dramatic relief, 1472t
Drawing, pain, 285, 289–290
DREZ. See Dorsal root entry zone (DREZ) lesioning
DRG. See Dorsal root ganglia
DRGS. See Dorsal root ganglion stimulation
Driving ability, opioids and, 697–698, 698t
Dronabinol

5585
 for cancer pain, 687
for cancer pain in children, 801
for cancer-related nausea/vomiting, 684
for central pain, 401t
for neuropathic pain, 1371t
for spinal cord injury pain, 592
Droperidol, 684, 715
DRt. See Dorsal reticular nucleus
Drug(s). See Pharmacotherapy; specific drugs
Drug Abuse Screening Test (DAST), 1509–1510
Drug Abuse Warning Network, 1773
Drug Addiction Treatment Act of 2000, 1006, 1515
Drug approval process, FDA, 175–176, 1313
Drug counseling, 1512
Drug Enforcement Administration (DEA), 176–177, 1314. See also
Controlled Substances Act
Drug eruptions, cutaneous, 556–557, 556f
Drug Misuse Index (DMI), 465
Drug-dependent person, 178–179, 184
Drug-induced liver injury (DILI), 986
Drug-seeking behavior
burn pain and, 905
in emergency department, 1773–1774
monitoring for, 1013–1014
Dry cupping, 1530
Dry needling, for myofascial pain (trigger points), 515–517, 516f
Dualism, 313, 410
Ductus deferens
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Due care, 193
Duloxetine
for abdominal pain, 1070
for acute pain, 832
for central pain, 400, 401t

5586
 for chemotherapy-induced peripheral neuropathy, 686
for children, 917
for chronic pelvic pain, female, 1086
for depression, 436, 438–439
for elderly patients, 933
for fibromyalgia, 536t, 537
for HIV pain, 994t, 995
for low back pain, 1271, 1295
for male pelvic pain, 1105
for migraine, 990t
for neuropathic pain, 400, 686t, 1360t, 1361–1362, 1361t
for painful neuropathies, 337
for postherpetic neuralgia, 384t, 386, 1186
side effects of, 400–402
for spinal cord injury pain, 591
Duodenum, sympathetic and nociceptive nerve supply to, 116t
Dura, of spinal cord, 39
Dural arteriovenous fistula, 255
Dural puncture, unintentional, 949
Dural puncture epidural analgesia, for childbirth pain, 949
Duration, of prescription, 179, 181–182, 181t, 182t
Duration of pain, 286, 566, 1262
Duration-based classification, 16
Duty of care, 193
Duty to relieve pain and suffering, 151, 152
DVPRS. See Defense and Veterans Pain Rating Scale
DVT. See Deep venous thrombosis
Dyclonine, for oral mucositis, 737
Dying
advance care planning for, 164–165
cancer pain in, 618, 1732–1733
decisional capacity in, 163
decision-making in, 160–162
consideration of medical and nonmedical factors in, 160
departures from ideal, 161–162

5587
 honesty v. hope in, 162
ideal, 160
joint participation in (doctor–patient), 160
patient attitudes and values in, 161
physician attitudes and values in, 161–162
prognosis and clinical judgment in, 161
surrogate, 163–165
ethics in, 159–171, 1732
contributions and limitations of, 159–160
espoused beliefs v. ability to act, 159–160
goals of analysis, 160
major themes in, 160
public consensus on, 159–160
existential distress in, 159, 1738–1739
ICU end-of-life care in, 1734, 1789, 1789t
moral order in, 159
myoclonus in, 1737
nonbeneficial treatment in
checklist on, 168, 168t
clinical context of conflict over, 166
differential diagnosis of conflict over, 166–167, 167t
ethical basis of conflict over, 166
information about, 167, 167f
intractable conflicts over, 167, 167t
resolvable conflicts over, 167, 167t
responding to demands for, 166–168
noncancer diagnoses in, 1733
opioid diversion in, 619
pain assessment in, 1733–1735
challenges in, 1733–1734
in cognitively impaired persons, 1734, 1734t
in nonverbal patients, 1734, 1734t
research in, 1735
pain management in, 1732–1743
fears of hastening death in, 1738

5588
 intractable pain or unmanageable adverse effects and, 1736–1739
nonpharmacologic, 1739
organ dysfunction and pharmacokinetics in, 1736
in patients with substance use disorder, 464–465
pharmacologic, 1735–1739
routes of drug delivery, 1735–1736
strategies for, 1735–1740
pain syndromes in, 1732–1733, 1734t
palliative care in, 205, 1732–1733
cancer-related, 763–765, 764f
for children with cancer, 802–803
definitions of, 160
doctor’s role and decision in, 160
integration of, 1732, 1733f
models of, 1732, 1733f
transition from curative care to, 160–163
palliative sedation in, 168–169, 1739–1740, 1739t
physician-assisted death in, 168–170
aggressive symptom management in, 168–169
Canadian Supreme Court decision on, 202
cessation of eating and drinking in, 169
clinical care in, 169–170
ethical considerations along clinical spectrum in, 168–169
legalization of, momentum in, 202
levels of response in, 169–170
prescription for lethal dose in, 169
sedation in, 169
social policy on, 169
steps for physicians in, 169
terminology for, 168
U.S. Supreme Court decision on, 201–202
social networks and systems in, 170
sociocultural perspective on, 140–141, 142
suffering in, 1738–1739
technological brinkmanship in, 161–162

5589
 treatment preferences in
actionable medical orders from, 165
communication about, 160, 162–163
informed consent for, 160
negotiating, 160
Dynamic mechanical allodynia, 34b
Dynamometer, 1503
Dynorphin, 46t, 48, 960
Dysesthesia, 13, 235
Dysfunctional patients, 18
Dysmenorrhea, 1083–1084
causes of, 1083, 1083t
endometriosis and, 1086
nonpharmacologic interventions for, 1072, 1084
NSAIDs for, 1069, 1071, 1083
surgical treatments of, 1084
Dyspareunia, 1089, 1090–1092, 1091t
Dyspepsia, nonulcer, 525
Dysphagia, abdominal pain and, 1064
Dysthymic disorder, 435
Dystonia, in complex regional pain syndrome, 345
Dystrophic changes, in complex regional pain syndrome, 344–345

E
Early life experiences, 295
EAST. See Elevated arm stress test
Eastern Cooperative Oncology Group Performance Status, 665t
EBM. See Evidence-based medicine
EBV. See Epstein-Barr virus
Eccentric exercise, 1497–1498, 1498t
Eccrine spiradenoma, 560, 561t
ECDD. See Expert Committee on Drug Dependence
Economic factors, for opioid analgesics, 218–219
ECS-CP. See Edmonton Classification System for Cancer Pain
Ectopic excitability, 1668
Ectopic generation of action potentials, 1668

5590
Ectopic pregnancy, 1079t, 1081
Eculizumab, for antiphospholipid syndrome, 548
Edema, neurogenic, 233
Edmonton Classification System for Cancer Pain (ECS-CP), 603, 605f
Edmonton Symptom Assessment Scale–Revised Version (ESAS-R), 603,
604f, 1734
EDPM. See European Diploma in Pain Medicine
Edrophonium (Tensilon) test, 1046
Education
patient, 480, 480t
on childbirth, 945
in cognitive-behavioral therapy, 1406–1407, 1455
on low back pain, 1541
on myofascial pain (trigger points), 515
on prescription medications, 187
provider (physician)
on complementary and integrative medicine, 1547
deficiencies in, 153–154, 216, 623–625, 1793
on pain, 153
in spine clinic, 1720–1721
Education for Physicians on End-of-Life Care Project (EPEC), 153
Education groups, for chronic pain, 1439
Educational history, and pain, 295–296
EEG. See Electroencephalography
Effectiveness
comparative, 132
efficacy v., 130
Efficacy
effectiveness v., 130
in pharmacotherapy, 1313
in prescription monitoring, 182
in trial of therapy, 1013
Effort syndrome, 1191, 1201t
EFNS. See European Federation of Neurological Societies
Ehlers-Danlos syndrome, 489, 569, 921

5591
Eight C’s, in explaining low back pain, 1254, 1254t
Eisenberg, D., on unorthodox medicine, 1546–1547
Elbow pain, after spinal cord injury, 583
Elder abuse, 197
Elderly, 929–939
acute pain management in, 839–840
cancer and cancer pain in, 599, 600, 601, 689
clinical evaluation of pain in, 930
complementary and integrative health approaches for, 934, 935
conditions associated with pain in, 929
group therapy for, 1447t
herpes zoster in, 1186
impact of pain on functioning and quality of life, 929
interventional therapies for, 934
multidisciplinary pain treatments for, 935
nonverbal, cognitively impaired, 930–931
pain measurement in, 288–289, 930–931
pain perception in, 839
pain processing and modulation in, 930
pharmacokinetics and pharmacodynamics in, 931
pharmacologic treatment of pain in, 931–934
adjuvant, 933–934
Beers criteria for, 931–932
nonopioid, 931–932
opioid, 931, 932–933
physical treatment modalities for, 934–935
postoperative delirium in, 839–840
prevalence of pain in, 929
psychosocial treatment modalities for, 935
undertreatment of pain in, 929–930
Electroanalgesia, 1526–1529. See also specific stimulation modalities
Electroconvulsive therapy, for residual limb pain, 368
Electrodermal therapy, intradiscal, 1647
Electrodiagnosis, 243–250
applications of, 249–250

5592
 in carpal tunnel syndrome, 249, 1175, 1673–1674
in Guillain-Barré syndrome, 249, 333
laboratory for, 243, 243f
in neck and arm pain, 1168
needle EMG in, 243, 246–249
nerve conduction studies in, 243–246
in neuropathy, 250, 330
in phantom pain, 364
tests in, 243–249
in thoracic outlet syndrome, 578
Electroencephalography (EEG), 62–63
in attention studies, 71, 71f
in complex regional pain syndrome, 343
in hypnosis, 1423
Electrogenic fish, 1570
Electromyography (EMG), 243, 246–249
applications of, 249–250
clinical significance of parameters in, 248t
concentric, 247, 247f
in entrapment syndromes, 1673
in femoral nerve entrapment, 1212
in fibular nerve entrapment, 1218
indications for, 246
insertional activity in, 248t
in lateral femoral cutaneous nerve entrapment, 1210
in lumbosacral plexopathy, 1205
monopolar, 247
motor unit potentials in, 248, 248f, 248t
in neck and arm pain, 1168
in neuropathy, 250, 330
in obturator nerve entrapment, 1215
in pes cavus, 1219
recruitment in, 248t
in saphenous nerve entrapment, 1214
in sciatic nerve entrapment, 1217

5593
 scoring system for, 248t
spontaneous activity in, 247–248, 247f, 248t
surface, 248–249
in tarsal tunnel syndrome, 1221
in thoracic outlet syndrome, 578
timing of, 246–247
Electromyography (EMG) machine, 243, 243f
Electronic date transfer, 182
Electronic health record, 231
Electronic pain assessment, 1305
Electronic pain diary, 274–276
Eletriptan, 1024t
Elevated arm stress test (EAST), 1166
Elimination (pharmacokinetics)
end-of-life organ dysfunction and, 1736
of local anesthetics, 1384
of NSAIDs, 1318
Elkins Hypnotizability Scale, 1425
Ellis, Albert, 1405, 1408
“Embeddedness” problem, 303–304
Embolism, of particulate steroids, 1765
Emergencies, 1758–1769
anaphylaxis, 1764–1765
cancer pain, 618–619
catastrophic neural injuries, 1765–1767, 1767f
infectious, 1760–1761
intrathecal drug delivery, 1764
pain clinic, 1758–1769
sickle cell pain, 974
spinal cord compression, 773
unintended destinations of local anesthetics, 1763
vasovagal reactions, 1763–1764
Emergency department
alternative delivery routes in, 1776–1777
analgesics administered in, 1775–1776, 1776t

5594
 balance in, 1774
discharge diagnoses in, 1770, 1770f
drug-seeking behavior in, 1773–1774
evolving practices in, 1778–1779
nonopioids in, 1775
oligoanalgesia, 1772, 1772t
opioid abuse in, 1772–1775
opioid analgesia in, 1775–1776
pain assessment in, 1771–1772
pain management in, 1770–1781
pain prevalence in, 1770–1771
patient-controlled analgesia in, 1776
procedural sedation and analgesia in, 1775, 1777–1778
sickle cell disease in, 1774–1775
Emergency Medical Treatment and Active Labor Act (EMTALA), 154
Emerging models of care, 1729–1730
EMG. See Electromyography
EMLA, 794, 903, 1386, 1389
Emory Pain Estimate Model (EPEM), 16–17
Emotion, 79–80, 410–424
adaptive functions of, 411
arousal in, 411
autonomic arousal in, 413
and behavior, 411
central limbic processing in, 414, 414f
central neuroanatomy of, 412, 412f
central neurotransmitter systems in, 414, 414f
and cognition, 410, 417–418
cognitive-motivational-relational theory of, 1395, 1395t
as component of pain, 79, 410
construction and modulation of pain, 417
definition of, 411
feedback in, 413
HPA axis in, 413–414, 416–417, 416f
interaction with pain, 79–80

5595
 locus coeruleus and dorsal noradrenergic bundle in, 414–415, 414f
measurement of affect, 276–278, 290
negative, and anger, 1394
noxious signaling in, 413–417, 414f, 416f
peripheral neuroanatomy of, 412–414
relationship between central and peripheral mechanisms in, 413–414,
413f
sociobiologic perspective on, 411
valence in, 411
ventral noradrenergic bundle in, 414, 414f, 416–417
Emotional distress, assessment of, 322
Emotional experience, in pediatric cancer pain, 790–791
Empathy, 480, 480t, 1749
Emphysema, spontaneous mediastinal, 1196t
Empirically based classification, of psychological components of pain, 18
Empirically based classifications, inductive, 21–22
EMTALA. See Emergency Medical Treatment and Active Labor Act
Enacarbil, for neuropathic pain, 686t, 1363t
Encephalitis, varicella-zoster, 376
“End” effects, 274
End of dose failure, 644
End of life. See Dying
Endocannabinoids, in stress-induced analgesia and hyperalgesia, 59
EndoCinch endoluminal gastroplication (ELGP), 1051
Endocrine therapy. See Hormonal therapy
End-of-life issues. See Dying
Endometriosis, 1086–1087
cutaneous, 560
hormonal treatments for, 1086t, 1087
medical management of, 1086–1087
novel concepts in, 1087
surgical management of, 1087
symptoms and signs of, 1086, 1086t
Endoscopy, upper, for noncardiac chest pain, 1042–1043, 1042t
Endothelin, in cancer pain, 627

5596
End-tidal carbon dioxide monitoring, 1777
Endurance, 1484
Energy crisis hypothesis, 504
Energy healing therapies, 1555
Energy-based therapies, 1549, 1552–1555
putative, 1552–1554
veritable, 1552–1553
Enforcement, of drug policy, 176–177, 187–188
Engagement, in patient encounter, 480, 480t
Engel, George L., 2, 7, 85, 447, 1392–1393
Enhanced recovery after surgery (ERAS), 826, 837
Enkephalins, 46t, 48, 118, 960
Enlisting patient involvement, 480, 480t
Enolic acid derivatives, 1316t
Enriched enrollment randomized withdrawal trials, 132
Ensuring Balance in National Policies on Controlled Substances: Guidance
for Availability and Accessibility of Controlled Medicines (WHO),
219
Enteral route, for end-of-life drug delivery, 1735
Enteric nervous system (ENS), 110, 118, 120f, 412
Enteritis, radiation, 755, 756–757
Enthesis, 493
Enthesitis, chronic, 495
Entrance strategy, for pharmacotherapy, 1012
Entrapment neuropathies, 267–268. See also specific nerves and
syndromes
clinical findings in, 1672–1673
electrodiagnostic studies in, 249, 1673
electrodiagnostic tests in, 249
in failed back surgery, 1289–1290, 1289t
imaging studies in, 1673, 1674f, 1675f
pathophysiology of pain in, 1672
release for, 1668, 1672–1678
and systemic disease, 1672
upper extremity, 1138, 1173–1174, 1174t

5597
Environmental factors, in spinal cord injury, 588
Environmental reevaluation, 1472t
EORTC QLQ-C30. See European Organisation for Research and
Treatment of Cancer Quality of Life Care Questionnaire
Eosinophilic granulomatosis with polyangiitis, 334, 545t, 547
EPEC. See Education for Physicians on End-of-Life Care Project
EPEM. See Emory Pain Estimate Model
Ephaptic conduction, 1669
Epidemic myalgia, 1190
Epidemic pleurodynia, 1190, 1195t
Epidermal cyst, inflamed, 555–556, 555f
Epidermal growth factor, in cancer pain, 627
Epidermal nerve fibers, 330
Epidermis, 543
Epidermoid tumor, painful trigeminal neuropathy with, 1117
Epidermolysis acquisita, 558
Epidermolysis bullosa, 558
Epididymal pain syndrome, 1098t, 1104
Epididymis, sympathetic and nociceptive nerve supply to, 117t
Epidural abscess, 1635, 1761, 1762f
Epidural analgesia, 1343, 1343f, 1385, 1385f
for acute pain
block technique in, 850–851
dosage recommendations for, 833t
local anesthetic–opioid combination in, 834
medications for, 833–834
outcome studies of, 835–836
patient-controlled, 835, 836t
risks of, 836
side effects of, 834–835
single-dose opioid, 833, 833t
thoracic, 850, 850t
for burn pain, 903
for childbirth pain, 940, 946–948
advantages and disadvantages of, 947t

5598
 caudal, 947t, 949–950
complications of, 949
drugs for initiating, 947–948, 947t
dural puncture, 949
maintenance of, 949, 949t
onset of, 947
patient-controlled, 949
side effects of, 949
complications of, 852–853
contraindications to, 853
for elderly patients, 934
emergencies and complications
bleeding, 1758–1760, 1760f
infectious, 1760–1761
malpractice claims over, 1758, 1759f
in end-of-life care, 1736
for infants and children, 818–819
drugs and drug dosing in, 818–819
positioning confirmation in, 818
in intensive care unit, 1787–1788
for neck pain, 1238
neural injuries in, 1765–1767, 1767f
patient-controlled, 851, 853
safety guidelines for, 1766–1767
for sympathetically maintained pain, 1684
training and credentialing for, 1756–1757
Epidural drug delivery, intrathecal v., 713, 1631, 1631t
Epidural fibrosis, in failed back surgery, 1292, 1295
Epidural hematoma, 1233, 1758–1760, 1760f
intrathecal drug delivery and, 1634–1635
management of, 1760
MRI of, 1760, 1760f
Epidural space, 1343, 1343f
Epidural spinal cord compression, 1183, 1197t
Epidural steroid injections (ESIs), 1611–1622

5599
 background of, 1611
blind, 1611, 1612, 1612t
caudal, 1611, 1612–1613
adverse events in, 1613
evidence on, 1612–1613
technique of, 1612, 1612f, 1613f
diagnostic phase of, 1611
image guidance for, 1611, 1612t
interlaminar, 1611, 1613–1615
adverse events in, 1615
evidence on, 1615
nonimage-guided v. image-guided, 1615
technique of, 1613–1614, 1614f
intradiscal, 1274, 1648–1649
local anesthetics with, 1611
techniques of, 1611, 1612t
transforaminal, 1611, 1615–1620
adverse events in, 1619–1620
alternative needle placements in, 1615, 1616f
for chronic back pain, 1274
CT guidance for, 1620
determinants of efficacy, 1619
evidence on, 1618–1619, 1620
for failed back surgery, 1289
for radicular pain, 1620
technique of, 1615–1618, 1616f, 1617f
Epinephrine
for acute pain, 834
for anaphylaxis, 1765
in autonomic nervous system, 118
in childbirth, 942
for childbirth pain, epidural, 947t, 948
in emotion, 412
intrathecal, 1626
in stress, 419

5600
E-prescriptions, 177
EPSPs. See Excitatory postsynaptic potentials
Epstein-Barr virus, 986, 1031
Eptinezumab, for migraine prevention, 1023
Equivalence trials, 132
ERAS. See Enhanced recovery after surgery
Erb, Wilhelm, 1109
Erectile dysfunction, pelvic pain and treatments causing, 1103, 1103t
Erector muscles of vertebral column, 1141, 1143f
Erenumab, for migraine prevention, 1023
Ergonomics, 1498, 1499t
Ergonovine stimulation test, 1046
Ergotamines
for cluster headache, 1134
for migraine, 989, 991t, 1023–1024, 1024t
Erickson, Milton, 1421, 1428, 1429, 1434–1435
Erikson, Erik, 1744–1745
Erysipelas, 553
Erysipeloid, 554
Erythema nodosum, 554, 554f
Erythrocyte sedimentation rate (ESR), 491, 494, 496, 502
in giant cell arteritis, 1031
in low back pain, 1252–1253, 1252t
in neck and arm pain, 1168
in vascular occlusive crisis, 962
Erythromelalgia, 559
acquired, 559
hereditary, 332–333, 559
Erythromycin, for bullous pemphigoid, 558
ESAS-R. See Edmonton Symptom Assessment Scale–Revised Version
Escitalopram
for abdominal pain, 1070
for depression, 439
for neuropathic pain, 1360t
Esdaile, John, 1421

5601
ESIs. See Epidural steroid injections
Esomeprazole, for GERD-related chest pain, 1051
Esophageal cancer, pain in, 638, 652, 1196t
Esophageal contractions, sustained, in noncardiac chest pain, 1039, 1047
Esophageal dysmotility
in fibromyalgia, 525
in noncardiac chest pain, 1038–1039, 1038f, 1045, 1195t
Esophageal evoked potentials, 1050
Esophageal hypersensitivity, in noncardiac chest pain, 1037, 1039–1040
Esophageal laceration and rupture, 1195t
Esophageal manometry, in noncardiac chest pain, 1038, 1038f, 1045–1046
Esophageal pain, in HIV/AIDS, 986
Esophageal pH monitoring, in noncardiac chest pain
ambulatory 24-hour, 1037, 1038, 1043
wireless, 1043
Esophagitis, 1195t
Esophagram, barium, for noncardiac chest pain, 1042
Esophagus
autonomic stimulation of, 119t
chest pain from disorders of, 1034, 1035t, 1195t–1196t (See also
specific disorders)
sensory afferent pathways of, 1046, 1046f
sensory testing of, 1046–1050
sympathetic and nociceptive nerve supply to, 115t
ESR. See Erythrocyte sedimentation rate
Es-reboxetine, for fibromyalgia, 537
Essential medicines, opioids as, 206
ESSIC. See European Society for the Study of Interstitial Cystitis
Estate of Henry James v Hillhaven Corporation, 196
Estimate’s Guide (INCB and WHO), 220
Estrogen, 94, 747
ESWT. See Extracorporeal shockwave therapy (ESWT), for plantar
fasciitis
Etanercept
for discogenic pain, 1649

5602
 for phantom pain, 367
for rheumatoid arthritis, 492–493, 492t
Etheric energy, 1552
Ethics
in death and dying, 159–171, 1732
contributions and limitations of, 159–160
espoused beliefs v. ability to act, 159–160
goals of analysis, 160
major themes in, 160
physician-assisted death, 168–170
public consensus on, 159–160
response to demands for nonbeneficial treatment, 166–168
transition from curative to palliative/end-of-life care, 160–163
in hypnosis, 1431–1432
narrative, 143–144, 1749
in pain management, 151–158
barriers to pain relief, 153–156, 676
core values of health care, 151–152
curative v. palliative paradigms, 152, 152t
duty to relieve pain and suffering, 151, 152
empathy and, 1749
Erikson’s Golden Rule and, 1744, 1745t
morals and, 1745
mutuality and, 1745, 1748–1749
opioid cessation, 1744–1750
opioid contracts, 156–157
pain relief as human right, 158
paradigm shift (new ethic) in, 151, 156–157
trust and, 1744–1745, 1748–1749
undertreatment, 151, 152–156
sociocultural perspective on, 143
Ethnic group differences, in pain, 94–96, 139–141
biopsychosocial mechanisms of, 95–96
in cancer, 600
clinical, 94–95

5603
 experimental, 95
interaction with other individual differences, 97
money/power and, 145
observational learning and, 428
treatment access and care, 139
treatment responses, 95
undertreatment, 95, 139–140
Ethnicity, self-identification of, 140
Ethnomedicine, 145
Etilefrine, for priapism, 969
Etiology-based classification, 16
Etodolac, 994t, 1316t, 1320
Etomidate, in emergency department, 1778
Etoricoxib, 1323
Eudynia, 16
Europe
pain medicine specialty in, 1754
pain medicine training in, 1755
European Academy of Anaesthesia, 1755
European Academy of Neurology, 404
European Association for Palliative Care, 798
European Association of Urology, 1096, 1098, 1103, 1105
European Diploma in Pain Medicine (EDPM), 1755
European Federation of Neurological Societies (EFNS), 1113, 1374–1375
European League Against Rheumatism, 1356
European Organisation for Research and Treatment of Cancer, 1734
European Organisation for Research and Treatment of Cancer Quality of
Life Care Questionnaire (EORTC QLQ-C30), 632, 632t
European Pain Federation, 1755
European Society for the Study of Interstitial Cystitis (ESSIC), 1096
European Union of Medical Specialists, 1754–1755
EuroQol, 232
Evacuation of retained products of conception, 1081
Evaluation. See Pain evaluation
Evidence-based CIH therapies, 1549–1550

5604
Evidence-based medicine (EBM)
in pain medicine, 1757–1758
in surgery for low back pain, 1283–1286
Evoked potentials
esophageal, 1050
somatosensory, 248
Exaggerated military position, 1166
Excessive pill loads, avoiding, 1013–1014
Excitatory amino acids, 45–47, 830
Excitatory postsynaptic potentials (EPSPs), 45
Executive attention, 71
Exercise prescription, 1498
Exercise therapy, 1498t. See also Physical therapy
for chronic pain, 1408
in cognitive-behavioral therapy, 1408
group, behavioral approaches v., 1456
definition of, 1537
for elderly patients, 934
for failed back surgery, 1294
graded, for fibromyalgia, 536t, 538
for low back pain, 1254–1255, 1272, 1278, 1456, 1537–1545
directional preference, 1540, 1542
elements of, 1538, 1538t
evaluation for, 1537, 1538f
evidence supporting, 1541–1543, 1543t
global, 1540–1543, 1543t
goal of, 1537
individualized program for, 1537, 1538–1541, 1543t
matching program to patient, 1542
musculoskeletal examination for, 1538
quota programs for, 1539
recommendations based on clinical course, 1539
relapse management in, 1540
spinal stabilization, 1540, 1541–1542
for opioid-induced bowel dysfunction, 683

5605
 for osteoarthritis, 489
recommendations for, 1540–1541, 1541t
for rehabilitation, 1497–1498
for spinal cord injury pain, 594
Exertional headache, primary, 1028, 1134
Existential distress, in dying, 159, 1738–1739
Exit strategy, for pharmacotherapy, 1012
Expectations, 76, 84–85, 476, 1406–1407, 1726
Experiential avoidance, 1416
Expert Committee on Drug Dependence (ECDD), 217
Expert-based classifications, of pain, 15
Expertise-based trials, 132
Expressive arts therapies, 701, 800–801
Extended connectivity, 53
Extended-release (ER) opioids, 175–176, 1342
Exteroception, 412, 412f
Extinction, 426
Extracorporeal shockwave therapy (ESWT), for plantar fasciitis, 1220
Extraspinal pathways, 45
Extremity pain
dorsal rhizotomy or ganglionectomy for, 1681–1682
joint, peripheral neurectomy for, 1672
lower, 1205–1227
foot, 1219–1226
lumbosacral plexopathy and, 1205–1208
nerve entrapment syndromes and, 1208–1219
peripheral nerve stimulation for, 1563
upper (See also Arm pain; Shoulder pain)
group therapy for, 1439
nerve blocks for, 1607
after spinal cord injury, 583
Eye
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Eye movement desensitization and reprocessing (EMDR), 368

5606
F
FABQ. See Fear Avoidance and Beliefs Questionnaire
Fabry’s disease, 332, 559–560
Face, Legs, Activity, Cry, and Consolability (FLACC) scale, 289, 790,
810, 822, 1772, 1783
Face pain scale, 288, 288f, 810
Faces Pain Scale–Revised (FPS–R), 288, 288f, 289, 290, 790, 914, 1783
Facet denervation, 1657
Facet joint injury, medical evaluation of, 315
Facet joint nerve blocks, 1275
Facet joint pain
cervical, 1485
in failed back surgery, 1290, 1290t, 1291, 1291t, 1294, 1295
treatment of, 1295
Facet rhizotomy, 1668
Facial expressions, 322
Facial nerve, 111, 112f, 1118, 1119f, 1162t
nervus intermedius neuralgia and, 1118–1119
Facial pain, 258, 1128–1137. See also Headache
atypical, 1108, 1108t, 1129
classification of, 1128, 1128t
cranial neuralgias (See Cranial neuralgias)
diagnostic imaging in, 258, 259f
odontogenic, 1113, 1130–1131
peripheral nerve stimulation for, 1565–1566
persistent idiopathic, 1108, 1108t, 1113
trigeminal neuropathy and, 258, 1128–1129
typical, 1108, 1108t
FACT. See Functional Assessment of Cancer Therapy
Factitious disorder, 299
Factorial design, 131
Failed back surgery (FBS), 1288–1297, 1299
definition of, 1288
diagnosis of, 1293–1294
differential diagnosis in, 1289t, 1291t

5607
 discogenic pain in, 1290, 1290t, 1291, 1291t, 1295
extraspinal causes of, 1289–1290, 1289t
history in, 1293
incomplete evaluation/diagnosis and, 1288–1289
location of pain in, 1293
mismatch or wrong surgery and, 1288
neuropathic etiologies of, 1288
neuropathic pain in, 1290, 1290t, 1291t, 1292, 1295
new pathology and, 1290
peripheral nerve stimulation for, 1564
preoperative v. current pain in, 1293
psychological factors in, 1289, 1292–1293
psychological interventions in, 1295
quality of pain in, 1293
radiologic evaluation of, 1294
recurrent pathology and, 1290
rehabilitation and exercise for, 1294
reoperation for, 1296
residual pathology and, 1289–1290
response to mechanical changes in, 1293
sacroiliac joint pain in, 1290, 1290t, 1291, 1291t, 1294, 1295
spinal causes of, 1289, 1290t
spinal cord stimulation for, 1573–1574, 1579
structural etiologies of, 1288, 1290–1292, 1290t
surgical complications and, 1289
technical failure and, 1289
time course of pain in, 1293–1294
treatment of, 1294–1295
Famciclovir, 377, 377t, 552–553
Family, 85
cancer pain and, 664
chronic pain in children and
assessment measures, 915
feedback, 915–916
impact, 911–912

5608
 trust for evaluation, 913
of dying patients
and demands for nonbeneficial treatment, 166–168
and drug diversion, 619
social support from, 296
as sociocultural system, 146
Family Assessment Device, 915
Family medical history, 238
Family systems, 85
Famotidine, 923, 1327
FAMs. See Fear-avoidance models
Farmer, Paul, 145
Fascia iliaca block (FIB), 875–876
clinical effects of, 875–876
complications of, 876
indications for, 875
landmark approach in, 875
techniques for, 875
ultrasound guidance for, 875
classic, 875
suprainguinal, 875, 875f
Fascia model, 1552
Fascia Research Society, 1552
Fascicles, 506
Fasciculations, 247–248
Fasciculus cuneatus, 40f
Fasciculus gracilis, 40f
Fatigue
cancer and, 630, 631–632
fibromyalgia and, 533–534
Fatigue Severity Scale, 632t
Fatigue Symptom Inventory Scale, 632t
FBS. See Failed back surgery
FCEs. See Functional capacity evaluations
FDA. See Food and Drug Administration

5609
Fear
assessment for, 322
in classical conditioning, 427–428, 427f
in low back pain, 1251, 1255–1256
Fear Avoidance and Beliefs Questionnaire (FABQ), 322
Fear of movement, 78, 80, 226, 227, 230
Fear of Pain Questionnaire, 915
Fear-Avoidance Beliefs Questionnaire, 230, 296, 1542
Fear-avoidance models (FAMs), 77, 78, 80, 1415–1416
in failed backed surgery, 1292–1293
in pain treatment outcome, 445
Febuxostat, for gout, 500
Federal Food, Drug, and Cosmetic Act of 1962 (FFDCA), 175–176
Federal Pain Research Strategy (NIH), 185
Federation of State Medical Boards (FSMB), 154, 180–181, 184, 194,
1313, 1723–1724
Feedback, and emotion, 413
Feldenkrais method, 1551
Fellowships, in pain medicine, 1751–1754
Femoral nerve, 868–869, 869f, 1205, 1211–1212, 1211f
Femoral nerve block (FNB), 871–872, 1607
for children, 821
clinical effects of, 872
complications of, 872
indications for, 871
landmarks for, 871, 871f
nerve stimulator-guided, 871
techniques for, 871–872
ultrasound guidance for, 871–872, 871f, 872f
Femoral nerve entrapment, 1211–1213
diagnosis of, 1212
etiology of, 1212
signs and symptoms of, 1212
surgery-related, 1212
treatment of, 1212–1213

5610
Femoral terminal branch, 882
Fenamates, 1316t
Fendiline, for noncardiac chest pain, 1052
Fennel oil, for abdominal pain, 1072
Fenoprofen, 1316t, 1321
Fentanyl, 1334t, 1345
for acute pain
continuous epidural, 833t, 834
intravenous patient-controlled, 832t
in opioid-tolerant patients, 840
single-dose neuraxial, 833, 833t
subarachnoid, 851–852
in war trauma, 838
buccal, 1735
for burn pain, 902, 903
for cancer pain, 689, 690, 690t, 693–695, 698–699
for cancer pain in children, 794, 798
for childbirth pain
combined spinal-epidural, 948–949, 948t
epidural, 947t, 948, 949t
for children, 794, 798, 814–815, 814t, 819t
consumption trends for, 208–215, 209f, 211f–214f
deaths associated with, 694–695
dose conversions of, 829t
in emergency department, 1776, 1776t, 1778
extended-release, 690t
hepatic dysfunction and, 689t
in intensive care unit, 1785
intranasal, 693t, 694
intrathecal, 714–715, 714t, 1625–1626, 1625t
for acute pain, 851–852
for neuropathic pain, 1375
trial of, 1631t
metabolites of, 1347t
morphine equivalence of, 208

5611
 nasal, 1735
nonparenteral, 693, 693t
oral transmucosal fentanyl citrate (OTFC), 1735
parenteral, 698–699
renal dysfunction and, 688t
side effects of, 836
subcutaneous, 1736
sublingual, 693t, 694, 1735
transdermal (See Transdermal fentanyl)
transmucosal, 693t, 694, 838
for cancer pain in children, 798
dose conversions for, 695t
for end-of-life pain, 1735
risk evaluation and mitigation strategy for, 694
for trigeminal neuralgia, 1115
urine testing for, 1016, 1509
Ferguson and Caplan classification, of cervical spondylotic myelopathy,
1170, 1170t
Fetal hemoglobin induction, in sickle cell disease, 975, 975t
Fetus
childbirth pain and, 942, 942f
neuraxial analgesia and bradycardia in, 949
Fever, neuraxial techniques and, 852–853
Feverfew, for migraine prevention, 1023t
FFDCA. See Federal Food, Drug, and Cosmetic Act of 1962
FIB. See Fascia iliaca block
Fibrillation potentials, 247, 247f
Fibrinogen, intradiscal, 1649
Fibroid degeneration, pelvic pain with, 1082
Fibromyalgia, 525–542
ACR criteria for, 526
adjuvant analgesics for, 685
animal models of, 528
anxiety in, 80, 440
brain imaging studies in, 529–530, 531f

5612
central sensitization in, 527–528, 528t, 529
in children, 910, 912, 916, 921
chronic widespread pain in, 526–527
CNS disturbances in, 529
as comorbid condition, 527
conditions simulating, 534, 534t
control points in, 526
cytokines or immune dysfunction in, 531
diagnosis of, 532–534
epidemiologic and observational studies of, 527–528
etiology of, 528–532
features of pain in, 532–533
gender differences in, 91–92, 526–527
genetic factors in, 528–529
global increase in sensory processing in, 529
group therapy for
acceptance-based, 1461, 1462t
cognitive-behavioral, 1442–1456, 1445t, 1449t, 1450t
mindfulness-based, 1457t, 1458t, 1459t, 1460t
historical perspective on, 525–526
key points on, 539
neuroendocrine and autonomic abnormalities in, 530–531
neurotransmitters in, 530, 530t
pain in, 485
pain narrative in, 143
patient education on, 534, 536t
pelvic pain in, 1089
peripheral factors in, 531
plasticity in, 72
posttraumatic stress disorder in, 1415
primary, 528
prognosis of, 539
recognition as illness, 445
risk factors for, 528
scoring in, 532, 532f, 533f

5613
 secondary, 527–528
sensory testing in, 530
sleep disturbance in, 437, 533–534
small fiber neuropathy in, 531–532
somatic symptoms in, 533–534
stressors in, 527, 527t
subsyndromic or subthreshold, 532
tender points in, 526–527, 534
top-down v. bottom-up, 528t
treatment of, 535–539
combination drug therapy in, 537
evidence-based therapies in, 536t–537t
general approach in, 535
neurostimulatory therapies in, 536t, 538
nonpharmacologic, 536t, 538
pharmacologic, 535–538, 536t–537t
Fibromyalgia Impact Questionnaire, 232, 537
Fibromyalgia Survey Criteria, 532, 532f, 533f
Fibromyalgianess, 532
Fibronectin-aggrecan complex, 1650
Fibrositis, 525–526
Fibular (peroneal) nerve, anatomy of, 1205, 1206f, 1217–1218, 1217f
Fibular nerve entrapment, 1217–1219
diagnosis of, 1218
etiology of, 1218
symptoms and signs of, 1218
treatment of, 1218–1219
FICA tool, for spiritual assessment, 143
Field block, 1386
15-Minute office visit, 1726–1727
Fifth vital sign, pain as, 141, 1771–1772, 1793
Fight or flight, 64, 79
Filgrastim, pain from, 651, 795
Finasteride, for prostate pain syndrome, 1104
Finland, topical NSAIDs in, 1319t

5614
First cervical nerve, 1145
First thoracic nerve, 1152t
First-degree burns, 897, 898f
Fishman, Scott, 138
Fitz-Hugh-Curtis syndrome, 1080
Five A’s of pain assessment, 236
Five A’s of treatment success, 1728, 1728t
5-Fluorouracil-induced chest pain, 754
FLACC. See Face, Legs, Activity, Cry, and Consolability (FLACC) scale
Flat palpation technique, 513–514, 514f
Flector, 1318, 1319t
Florida, litigation over pain management in
administrative proceedings, 194–195
criminal, 199
Fluconazole, prophylactic, 738
Flunarizine, for migraine prevention, 1023t, 1133
Fluorodeoxyglucose (FDG), 62
Fluoroquinolones, resistance, in pelvic inflammatory disease, 1080
Fluoroscopy, 268
for celiac plexus neurolysis, 718, 718f
for epidural steroid injections, 1611, 1612t
caudal, 1612, 1612f, 1613f
interlaminar, 1613–1614, 1614f
transforaminal, 1615, 1616f, 1617f, 1618–1619
for nerve blocks, 1597
for percutaneous cordotomy, 1700
for peripheral nerve device implantation, 1560–1561, 1560f
for radiofrequency rhizotomy, 1694, 1695f
for trigeminal nerve block, 723–725, 724f
Fluoxetine
for depression, 439
for fibromyalgia, 535, 537t
for HIV pain, 996
for neuropathic pain, 1360t, 1361t, 1362
Flurbiprofen, 1316t

5615
Flutamide, for priapism, 969
Fluvoxamine, 439, 1133
FM. See Fibromyalgia
fMRI. See Functional magnetic resonance imaging
FNB. See Femoral nerve block
Focal neuropathic syndromes, 334–335
Focal pain, 566
Focused attention, 70
Fohat, 1552
Foley, Kathy, 1751
Folic acid, for livedoid vasculitis, 548
Follow-up
in children, 916
in clinical trials, 128
in interdisciplinary chronic pain management, 1713–1714
in low back pain, 1256
in pain assessment, 236, 241
Food and Drug Administration (FDA), 175–176
cancer drugs approved by, 778–779
coating agents approved by, 737
dorsal root ganglion stimulation approval by, 1558, 1560
drug approval process of, 175–176, 1313
drug classification for pregnancy/lactation, 951–952
intrathecal agents approved by, 714, 714t, 1624
lasers and laser therapy approved by, 1524
medications approved for substance use disorder, 1515
neuraxial injection guidelines of, 1766–1767
new device regulation by, 1756
peripheral nerve stimulation devices approved by, 1559–1560
warning on NSAIDs, 1324–1325, 1325t
Foot pain, 1219–1226. See also specific causes
Foraminal stenosis, in failed back surgery, 1290–1291, 1290t, 1291t, 1295
Fordyce, Wilbert E., 138, 426–427, 1405, 1490, 1497, 1709
Forebrain, 62
Forensic pain medicine, 193

5616
Forward surgical teams (FSTs), in war zones, 838
Fos protein, 38–39, 41
Fosaprepitant, for nausea/vomiting in cancer therapy, 684
Foscarnet, for herpes zoster, 377t, 378
Fothergill, John, 1109
Foucault, Michael, 144–145
4 A’s, of pain medicine, 1008
4 E’s, of patient encounters, 480, 480t
Fournier gangrene, 552
Fox, Ellen, 152, 155
FPS–R. See Faces Pain Scale–Revised
FR. See Functional restoration
Fractionation, in hypnosis, 1433
Fracture, pathologic, 770–772, 771f
Frailty, 600
France, topical NSAIDs in, 1319t
Franklin, Benjamin, 1558
Freiberg sign, 1217
Fremanezumab, for migraine prevention, 1023
French-Language Society of Pediatric Anesthesiologists, 819
Frequency of pain, 286
Frequency of urine testing, 1015
Frequency-specific microcurrent (FSM), 1553
Freud, Sigmund, 447, 1382, 1392, 1423
Freudian theory, 2, 7
Fringe medicine, 1546
Fringe Medicine (Inglis), 1546
Frontal lobe, 62f
Frovatriptan, 990t, 1024t, 1028
Frozen shoulder, 658, 748
FRQ. See Functional Recovery Questionnaire
Frustration, 81–82
FSM. See Frequency-specific microcurrent
FSMB. See Federation of State Medical Boards
Fuller, Buckminster, 1552

5617
Fully programmable pumps, 1632
Function (functioning)
anxiety and depression impact on, 1414–1415
assessment of, 227, 232, 238, 241, 296, 323, 1303t, 1304–1305
childhood cancer and, 791
classification based on, 16
current, 296
definition of, 1492
pain interference with, 286–288
rehabilitation and, 1492
self-report measures of, 323
in spine surgery candidates, 1303t, 1304–1305
Functional Assessment of Cancer Therapy: Fatigue (FACT-F), 632, 632t
Functional Assessment of Cancer Therapy: General (FACT-G), 664, 666t
Functional Assessment of Cancer Therapy—General, 1734
Functional capacity, residual, 14
Functional capacity evaluations (FCEs), 1498, 1501–1503
assessment tools for, 1502
invalid, 1503, 1504t
lifting protocols in, 1502, 1503t
purposes of, 1502
types of, 1502
utility of, 1503
Functional chest pain, 1034, 1035t, 1036t
Functional Disability Inventory, 914
Functional gastrointestinal disorder, 525, 911, 923
Functional imaging of pain
in anterior cingulate cortex, 67
in attention studies, 71, 71f
in fibromyalgia, 529–530, 531f
gender differences in, 841
in headache, 1020, 1020f, 1021f
in humans, 62–63
in insula, 67
methodologies of, 62–63

5618
 in noncardiac chest pain, 1050
in plasticity, 72, 72f
in prefrontal cortex, 68–70, 69f
in primary somatosensory cortex, 66–67, 66f
in secondary somatosensory cortex, 67
Functional limitation, 1492
Functional magnetic resonance imaging (fMRI), 62–63
in complex regional pain syndrome, 343, 345
of esophagus (brain–gut relationship), 1050
in females v. males (differences in pain), 841
in fibromyalgia, 529–530, 531f
of habituation, 71
in hypnosis, 1423–1424
in phantom pain, 367
in plasticity, 72, 72f
in primary somatosensory cortex, 66–67
in secondary somatosensory cortex, 67
Functional neuroanatomy
of autonomic nervous system, 110–119
of central nervous system, 106–110
of enteric nervous system, 110, 118, 120f
of nociceptive system, 103–122
of peripheral nervous system, 103–106
Functional neurologic symptom disorder, 299, 446, 447, 447t
Functional Rating Scale, 1305
Functional recovery interventions, 309
Functional Recovery Questionnaire (FRQ), 309
Functional restoration (FR), 1712
in complex regional pain syndrome, 349–350, 350f, 355
elements of, 1491
history of, 1491
interdisciplinary programs for, 1494–1495
in low back pain, 1274
team-centered approach in, 1491
work rehabilitation in, 1501

5619
Functional somatic syndromes, 525, 528t
Functional status, 14
Funding source, effects on study, 130
Fundoplication, laparoscopic, 1054–1055
Funicular pain, 662
Furunculosis, 553–554
Future of pain medicine, 1793–1794
F-wave study, 245, 246f

G
G protein-coupled receptor, 1333
GABA. See Gamma-aminobutyric acid
Gabapentin
for abdominal pain, 1069–1070
for acute pain, 830–831
for bone pain in cancer, 745
for burn pain, 902
for cancer pain, 745, 757
for central pain, 400, 401t, 402, 402f
for chemotherapy-induced peripheral neuropathy, 686
for children, 812, 812t, 916, 917, 918
for chronic pelvic pain, female, 1086
for complex regional pain syndrome, 352
for elderly patients, 933
for erythromelalgia, 559
for Fabry’s disease, 560
for failed back surgery, 1295
for fibromyalgia, 530, 537, 537t
for herpes zoster, 378, 379t
for HIV pain, 994t, 996–997
in intensive care unit, 1787
intrathecal, 1627
for male pelvic pain, 1105
for migraine, 990t
for neuropathic pain, 400, 402, 686t, 1362, 1363t
for painful neuropathies, 336–337

5620
 for phantom pain, 365, 795
for postherpetic neuralgia, 383–386, 384t, 388, 1118
for postherpetic neuralgia prevention, 390
for sensory mononeuropathies, 559
side effects of, 402
for spinal cord injury pain, 590, 591
for trigeminal neuralgia, 1114–1115
for vulvodynia, 1092
Gabapentinoids. See also Gabapentin; Pregabalin
for spinal cord injury pain, 590, 591
GAD. See Generalized anxiety disorder
Gain control mechanisms, 52, 53
Galanin, 45, 46t, 49, 827
Galcanezumab, for migraine prevention, 1023
Galen, 1, 2–3, 1492, 1492t, 1497
Gallagher, Rollin M., 1751
Gallbladder
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Gallium nitrate, for bone pain in cancer, 777–778
Gallstones, in sickle cell disease, 966
Gamma knife surgery
for thalamotomy, 1703–1704
for trigeminal neuralgia, 1116, 1695–1696
Gamma-aminobutyric acid (GABA), 46t, 47, 48, 49
in acute pain, 827
in cancer pain, 733
in fibromyalgia, 530
in muscle physiology, 1353
in muscle relaxant effects, 1354, 1355
in nociceptive modulation, 55t, 60
in spinal cord stimulation, 1571–1572, 1572f
Gamma-aminobutyric acid agonists. See also Baclofen
intrathecal, 1627
Gamma-aminobutyric acid receptors, 32–33

5621
Gamma-hydroxybutyrate, for fibromyalgia, 530, 537, 537t
Ganciclovir, for oral mucositis prophylaxis, 738
Ganglia, of ANS, 110–114, 110f, 111f. See also specific ganglia
Gangliolysis, for trigeminal neuralgia, 1115–1116
Ganglion of impar (Walther) block, 720–721, 720f, 759
Ganglionectomy, 1668, 1678–1682
basic considerations in, 1678–1679
clinical considerations in, 1679–1680
indications and outcomes, 1680–1682
operative technique of, 1680
preoperative evaluation for, 1679–1680
Gangrene, 569–570
Gardner’s syndrome, 556
Gas chromatography/mass spectroscopy (GC/MS), 1015, 1016, 1509
Gas entrapment syndromes, 1201t
Gastric pain, in cancer, 652
Gastrin-releasing peptide, 48
Gastroduodenal artery aneurysm, 1246
Gastroesophageal reflux disease (GERD)
ambulatory 24-hour esophageal pH monitoring in, 1037, 1038, 1043
barium esophagram in, 1042
epidemiology of, 1034
noncardiac chest pain in, 1034, 1195t
diagnosis of, 1042–1045
esophageal hypersensitivity in, 1037, 1037f, 1039–1040, 1040f
management of, 1038
pathophysiology of, 1036–1038
treatment of, 1051, 1054–1055
ultrasound studies of, 1037–1038
proton pump inhibitor test in, 1043–1044
upper endoscopy in, 1042–1043, 1042t
wireless pH system in, 1043
Gastrointestinal cancer, chemotherapy for, 781
Gastrointestinal pain, in HIV/AIDS, 986
Gate control model, 6, 18, 52, 52f, 60, 83, 1492, 1492t

5622
 anatomic and physiologic focus of, 85
impact of, 83
molecular gaze and, 143–144
in peripheral nerve stimulation, 1558–1559
somatic and psychogenic factors in, 83
in spinal cord stimulation, 1299, 1570
supraspinal systems in, 54, 54f
GCH1 gene, 96–97
G-CSF. See Granulocyte colony-stimulating factor
GDNF. See Glial cell line-derived neurotrophic factor
Gender bias, in pain treatment, 93
Gender differences, in pain, 91–94, 140–141
in acute pain management, 841–843
biopsychosocial mechanisms of, 94
clinical, 91–92, 841–842, 842t
experimental, 92–93, 842–843
in fibromyalgia, 91–92, 526–527
functional imaging of, 841
in HIV/AIDS, 985
interaction with other individual differences, 97
in noncardiac chest pain, 1034, 1041
observational learning and, 428
in pharmacokinetics, 1103
postoperative, 92
treatment responses, 93–94, 140
in unexplained pain syndromes, 525
Gender roles, 94, 140
Gene therapy, for sickle cell disease, 977–978
General adaptation syndrome, 79
General physical exam, 233
Generalizability of results, 130
Generalized anxiety disorder (GAD), 227, 229, 298, 322, 441–442, 441t,
1417
Generator potential, 26, 30
Genetics and pain, 96–97

5623
 candidate gene studies of, 96–97
clinical, 96
experimental, 96–97
interaction with other individual differences, 97
twin studies of, 96
Geniculate neuralgia. See Nervus intermedius neuralgia
Genitalia, male, nerves and, 1102
Genitofemoral nerve, 868–869, 869f
anatomy of, 1205, 1206f
in pelvic pain, 1102
Genitourinary medicine (GUM) clinic, 1080, 1092
Gepants, for migraine, 1024
GERD. See Gastroesophageal reflux disease
German Pain Society, 1755
German Research Network on Neuropathic Pain, 330, 343
German Society of Anaesthesiology, 1755
Gestrinone, for endometriosis, 1086t
GEXP. See Graded exposure
GFR. See Glomerular filtration rate
Giant cell arteritis, 502, 569, 1031
Gilliatt-Sumner hand, 576, 1176
Ginger, for abdominal pain, 1072
Gingivitis, 1130
Girdle syndrome, 968
Glenohumeral joint, 1156–1158, 1158f, 1159t, 1485–1486
Glia, neurotransmitters from, 49–50
Glial cell line-derived neurotrophic factor (GDNF), 46t, 49–50, 106
Global Atlas of Palliative Care at the End of Life, 205
Global Burden of Disease Initiative, 484, 1298
Global Burden of Disease Study 2013, 1158
Global exercise, for low back pain, 1540–1543, 1543t
Global health assessment, 227, 232, 237
Global Opioid Policy Initiative (GOPI), 215, 218
Globalization, and pain, 144–146
Glomerular filtration rate (GFR)

5624
 NSAIDs and, 1327–1328
opioid dosage based on, 688
Glomus tumor, 560, 560f, 561t
Glossopharyngeal nerve, 111, 112f, 1162t
Glossopharyngeal neuralgia, 1120, 1129
cancer-related, 653
treatment of, 1120, 1122, 1129
trigeminal neuralgia v., 1112
Glucocorticoids
for acute pain, 831
for calcium pyrophosphate deposition disease, 497
for cancer pain (bone), 686
for giant cell arteritis, 502
for gout, 500
for polymyalgia rheumatica, 502
for rheumatoid arthritis, 493
Glucosamine, 1649
Glucose tolerance, impaired, 331, 335
Glutamate, 45–47, 46t, 107
in acute pain, 830
in cancer pain, 732
in spinal cord injury, 110
Glutamate receptors
in acute pain, 827
ionotropic, 45–47
metabotropic, 47, 827
Gluteal abscess, 1208
Gluteal pain, 1245–1246
Glycerol injection
for neurolytic blockade, 1653, 1654
for trigeminal neuralgia, 1115, 1653, 1654
Glycine, 46t, 48, 49
in acute pain, 827
in nociceptive modulation, 55t
GM-CSF. See Granulocyte-macrophage colony-stimulating factor

5625
Goals, in pain evaluation, 232–233, 240–241
Golden Rule, Erikson’s, 1744, 1745t
Goldscheider, Alfred, 4, 4f, 6
Golimumab, for rheumatoid arthritis, 492–493, 492t
Gonococcal arthritis, 501
Gonorrhea, pelvic inflammatory disease in, 1080
Gonzalez v Oregon, 202
Gonzalez v Raich, 202–203
Good pain (eudynia), 16
GOPI. See Global Opioid Policy Initiative
Gordon, Kathleen, 479
Gout, 484, 497–500
arthritis in, pathophysiology of, 498–499
etiology and pathophysiology of, 498, 1224
foot pain in, 1224
historical perspective on, 497
laboratory findings in, 499, 1224
neck pain with, 1233
primary, 498
radiography of, 499, 499f
secondary, 498
signs and symptoms of, 499, 499f, 1224
tophaceous, 499, 499f
treatment of, 499–500, 1224
Gowers, Sir William, 4, 525
Graded activity, 1497
Graded Chronic Pain Rating Scale, 228, 229
Graded exercise, for fibromyalgia, 536t, 538
Graded exposure (GEXP), 1529
Graded motor imagery, 350–351, 368, 1497, 1531–1532
Grading of Recommendations Assessment, Development, and Evaluation
(GRADE), 400
Grading system, for central pain, 396–397, 396f
Graft-versus-host disease, 661, 797
Granisetron, for nausea/vomiting in cancer patients, 684

5626
Granulocyte colony-stimulating factor (G-CSF), pain from, 651, 795
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
for oral mucositis prevention, 738–739
pain from, 748, 795
Granuloma, intrathecal, 715, 1638–1639, 1639f
Granulomatosis with polyangiitis, 334, 544t, 547
Graphical rating scale (GRS), 1771–1772
Gray communicating ramus, 113–114
Great auricular nerve, 1146, 1146f
Greater occipital nerve, 1145–1146, 1146f
Greater occipital nerve block, 1171, 1598f, 1605, 1607
Greater trochanteric pain syndrome, 1289–1290, 1289t
Grey matter, of spinal cord, 39–42, 41f
Grip strength, 1503
Groin, anterior nerves of, in pelvic pain, 1090, 1102
Groin pain, peripheral nerve stimulation for, 1564–1565
Groopman, Jerome, 1717
Group therapy, for chronic pain, 1439–1469
acceptance-based, 1439, 1456–1461, 1462t
advantages of, 1463–1464
behavioral v. exercise and physical therapy, 1456
CBT v. wait-list, treatment as usual, or other group treatments, 1442–
1456, 1443t–1454t
cognitive change in, importance of, 1461–1463
compliance with homework and practice skills in, 1463
education, 1439
efficiency and cost-effectiveness of, 1463–1464
evidence for efficacy of, 1439
factors affecting outcome, 1461–1463
future directions of, 1465–1466
group processes in, 1463
individual treatment v., 1439–1442, 1440t–1441t
individuals inappropriate for, 1465
interpersonal process in, 1464
length of, 1465

5627
 mindfulness-based, 1439, 1456, 1457t–1460t
number of participants, 1465
open v. closed, 1464
practical issues in, 1464–1465
search strategies for literature on, 1466
social proximity and support in, 1464
supportive/expressive, 1439
therapist skill and time in, 1463
vicarious learning and modeling of collaborative approach in, 1464
Growth factors, 46t, 48
Growth hormone, 435
GRS. See Graphical rating scale
Guide on Estimating Requirements for Substances Under International
Control (INCB and WHO), 220
Guided imagery, 1407
Guidelines for the Chronic Use of Opioid Analgesics, 181, 1313
Guillain-Barré syndrome, 329–330, 333–334
cancer-related, 657
electrodiagnostic tests in, 249, 333
in HIV/AIDS, 988–989
Gunshot Wounds and Other Injuries of Nerves (Mitchell), 9
Gynecomastia, tumor-related, 755

H
HAART. See Highly active antiretroviral therapy
Habit assessment, 231, 240
Habituation, 71
HAD. See Hospital Anxiety and Depression Questionnaire
Haemophilus influenzae
in acute splenic sequestration crisis, 968
in HIV/AIDS, 987
Hahnemann, Samuel C., 7, 1554
Hair follicles, sympathetic and nociceptive nerve supply to, 115t
Haley, Jay, 1421
Half-life, of opioid analgesics, 1340, 1340t
Hallux rigidus, 1223, 1223f

5628
Hallux valgus, 1222–1223, 1222f
Haloperidol
for burn pain, 902
for nausea/vomiting in cancer therapy, 683–684, 684t
for palliative sedation, 1739t
Halsted maneuver, 1166
Hammertoe deformity, 1225, 1225f
Hand–foot syndrome (dactylitis), 493, 494f, 968
“Hands-up” test, 577
Harborview Medical Center/University of Washington Burn Center
guidelines, 901t
Hard corn, 1225–1226
Harms, assessment of, 130–131
Harrison Act of 1914, 1519
Harvard Group Scale of Hypnotic Susceptibility, 1425
Harvey, William, 3
Hawaii, addiction-related terminology in, 183t
HCT. See Hematopoietic cell transplantation
Head and neck, sympathetic and nociceptive nerve supply to, 115t
Head and neck cancer, 732–743
chemotherapy for, 736, 780–781
chemotherapy-related pain in, 733
cognitive-behavioral therapy in, 739
combination therapy in, 736
interventional pain therapies in, 723–725
oral mucositis in, 661, 734–739
chemotherapy and, 736
epidemiology of, 734, 734t
hematopoietic cell transplantation and, 734, 735, 735f, 737, 738, 741
hyposalivation and, 738–739
management of, 736–737, 737t
pain management for, 737–740, 740t
pathogenesis of, 734–735, 734f, 735t
pediatric, 821
prevention of, 737, 737t, 738–740

5629
 radiation therapy and, 735–737, 736f
stepped protocol for, 737
pain in
assessment of, 736
mechanisms of, 732–733
orofacial, 732, 732t
radiation therapy-related, 733, 735–736, 736f
surgery-related, 733–734
tumor type and stage of disease in, 638
Headache, 1019–1033. See also Migraine; specific types
acute, 251–256, 1029
aneurysm in, 251, 252f, 255, 1029
arterial dissection in, 251, 255f
AVM in, 251, 253f, 255
CT in, 251, 252f, 253f, 254–255, 1029
CTA in, 251, 253f, 255–256, 255f
MRA in, 251, 254f, 255–256, 1029
MRI in, 254–255, 1029
“thunderclap” or “sudden worst,” 251, 1029
venous sinus thrombosis in, 251, 254f, 255, 255f
cerebrospinal fluid and, 1030–1031, 1030f
in childhood cancer, 793
in children, 910, 922–923
chronic, 256–257, 1021–1022, 1133–1135
CT in, 256–257
CTA in, 256
differential diagnosis of, 256
MRA in, 256, 256f, 257f
MRI in, 256
sinusitis and, 256–257, 257f
classification of, 1019, 1128, 1128t
common causes of, 1019t
diagnostic imaging in, 251–258, 1021
indications for, 251
yield in, 251, 251t

5630
epidemiology of, 251
functional imaging in, 1020, 1020f, 1021f
gender differences in, 91
genetics and, 96
greater occipital nerve block for, 1607
group therapy for, 1439
acceptance-based, 1462t
cognitive-behavioral, 1442, 1444t, 1446t, 1450t, 1451t, 1453t, 1454t,
1455
compliance with homework and practices skills in, 1463
individual treatment v., 1441t
mindfulness-based, 1457t, 1458t
history of, 1021
in HIV/AIDS, 989–992
migraine, 989, 990t–991t
primary, 989
secondary, 989–992
hypnosis for, 1430–1431
intracranial hypertension and, 258
intracranial hypotension and, 257–258
malpractice claims over, 1759f
neurovascular, 1019
panic disorder and, 442
peripheral nerve stimulation for, 1565–1566
postdural puncture, 715, 948, 1635
postlumbar puncture, 795
primary, 1019–1020, 1133–1134
anatomy and physiology of, 1019–1020, 1020f
disabling, 1019
secondary, 1019, 1020–1021, 1031, 1031t, 1134–1135
short-lasting, 1025–1027
differential diagnosis of, 1026, 1026t
SUNA syndrome, 1026, 1026t, 1027, 1135
SUNCT syndrome, 1026, 1026t, 1027, 1113, 1135
spinal cord injury and, 582, 584

5631
 thoracic outlet syndrome and, 576
vascular, 1019
warning signs in, 1019t
Headacheyness, 1024
Healing phase, in burn injury, 898
Healing touch (HT), 1554, 1555
Health and Retirement Study, 94, 95
Health status, 14
Health-related quality of life. See Quality of life
Healthy life expectancy, 1158
Hearing loss, NSAIDs and, 1328
Heart
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Heat, for neurolytic blockade, 1653. See also Thermal radiofrequency
neurotomy
Heat therapy, 1522–1523
for costochondritis, 1189
for dysmenorrhea, 1072, 1084
for low back pain, 1254
for manubriosternal arthritis, 1190
for myofascial pain, 1190
for prostate pain syndrome, 1104
Heberden’s nodes, 487, 488f, 499
Hedblom syndrome, 1196t
Heel pad deficiency, 1220
Helicobacter pylori, 1327
Helping relationships, 1472t
Helplessness, 84
Hematocolpos, 1081
Hematologic effects, of NSAIDs, 1327
Hematoma
epidural, 1233, 1634–1635, 1758–1760, 1760f
intrathecal drug delivery and, 1634–1635
nerve block and, 887

5632
 retroperitoneal, 1208
Hematometra, 1081
Hematopoietic cell transplantation (HCT)
bone marrow expansion after, 795
cognitive-behavioral therapy in, 739
graft-versus-host disease in, 661, 797
oral mucositis with, 734, 735, 735f, 737, 738, 741, 795
Hemi-attention, 229
Hemibody radiation, 776–777
Hemicrania, paroxysmal, 1026, 1026t, 1027, 1113
Hemicrania continua, 1027, 1029
Hemifacial spasm, 1112
Hemochromatosis, 489
Hemodialysis, and opioid therapy, 687–688, 688t
Hemoglobinopathies, 955. See also Sickle cell disease
Heparin
for antiphospholipid syndrome, 548
bleeding complications with, 1758, 1759
for livedoid vasculitis, 548
Hepatic artery infusion pain, 756
Hepatic crisis, in sickle cell disease, 967, 967f
Hepatic disease/dysfunction
comorbid with cancer, 601
and local anesthetics, 1384
and NSAID therapy, 1318
and opioid therapy, 688–689, 689t
Hepatic distention syndrome, 755
Hepatic injury, drug-induced, 986
Hepatic sequestration, in sickle cell disease, 967
Hepatic toxicity, of NSAIDs, 1328
Hepatic tuberculosis, in HIV/AIDS, 986
Hepatitis C, 331, 546
Herbal (natural) medicine, 801, 1549, 1551
Hereditary neuralgic amyotrophy, 335
Hereditary neuropathies, 332–333

5633
Hernia, chronic pelvic pain with, 1089
Heroin, urine testing for, 1509
Herpes simplex virus (HSV), 552–553, 552f
in cancer, 735, 738, 754, 797
in HIV/AIDS, 986
Herpes zoster, 335, 372–395, 552. See also Postherpetic neuralgia
analgesia for, 378, 379t, 391
antiviral therapy for, 377–378, 377t, 391
cancer treatment and, 782, 797
chest wall pain in, 1185–1186, 1197t
clinical picture and natural history of, 372–373, 373f, 1117
clinical variants of, 373
complementary and integrative health in, 379
complications associated with, 376
corticosteroids for, 378
decreased quality of life in, 376
diagnosis of, 374, 1118
distribution of, 372–373, 374f, 374t
epidemiology of, 374–375, 375t, 1118
herpes simplex v., 374
laboratory testing in, 374
motor neuropathy in, 376, 376f, 381
neural blockade for, 378–379
pain in, 372, 375–376
painful trigeminal neuropathy in, 1117–1118
pathophysiology of, 375–376, 375f
patient education in, 376–377
prevention of, 380, 1118
prodrome in, 372
rash in, 372, 372f, 374
spinal cord stimulation for, 380
treatment of, 376–380, 391, 1118, 1186
underlying disorders in, 374
Herpes zoster ophthalmicus (HZO), 373, 373f, 376, 1113
Herpes zoster oticus, 373

5634
Herpes zoster vaccination, 380, 390, 391
Herrick, James B., 955
Heshusius, Lous, 139
Hétero Evaluation Douleur Enfant (HEDEN), 790
Heterosegmental modulatory systems, 53
Heterotopic pregnancy, 1081
Hiatal hernia, paraesophageal, 1196t
Hidradenitis suppurativa (HS), 554–555, 555f
High threshold neurons, 42
High-frequency spinal cord stimulation, 1572–1573
High-impact pain, 1490, 1722
Highly active antiretroviral therapy (HAART)
liver injury with, 986
neuropathy in, 331
Hindbrain, 62
Hinton, John, 159
HIP. See Hypnotic Induction Profile
Hip disorders, and failed back surgery, 1289–1290, 1289t
Hip girdle pain, 1487–1488
Hippocampus, 62, 70
in learning and memory, 70
in pain processing, 70
subdivisions of, 70
Hippocrates, 1, 1315, 1492, 1492t, 1497
Hippocratic Oath, 1745
Hispanics
money/power and, 145
pain and pain response in, 94–95, 139–140
pain management during dying, 142
responses to pain treatment in, 95
undertreatment of pain in, 95, 139–140
Histamine
in stress, 419–420
in vascular occlusive crisis, 960
Histamine 2 receptor blockers

5635
 for anaphylaxis, 1765
for gastric protection with NSAIDs, 1327
for GERD-related chest pain, 1051
HIV/AIDS
epidemiology of, 985
headache in, 989–992
migraine, 989, 990t–991t
primary, 989
secondary, 989–992
herpes zoster in, 374, 375
money/power and access to care, 145
neuraxial techniques in, 853
neurologic manifestations of, 987–989
osteoporosis and osteopenia in, 987
pain evaluation in, 992, 992f
pain in, 985–1000
abdominal, 986
anorectal, 986–987
chest pain syndromes, 987
chest wall, 987
in children, 985
epidemiology of, 205
esophageal, 986
gastrointestinal, 986
musculoskeletal, 987
nociceptive v. neuropathic, 992–993, 992f
oropharyngeal, 986
prevalence of, 985
pulmonary/pleuritic, 987
in women, 985
pain management in, 992–997
acetaminophen in, 993
antidepressants in, 994t, 995–996
antiepileptic drugs in, 994t, 996
barriers to, 997

5636
 cannabinoids in, 996
combination pharmacotherapy in, 996–997
drug–drug interactions in, 995, 995t
international initiatives on, 220
multimodal approach in, 992
nerve growth factor in, 996
nonopioid, 993, 994t
nonpharmacologic, 997
NSAIDs in, 993
opioid, 205, 993–995, 994t
pharmacologic, 992–997
topical capsaicin in, 996
WHO analgesic ladder for, 205, 993, 993f
pain measurement/assessment tools in, 992
painful neuropathies in, 331, 987–989, 988t
palliative care in, 205
undertreatment of pain in, 997
Hodgkin lymphoma, 643, 780
Hoffman, Felix, 1315
Holistic practice, 1546. See also Complementary and integrative health
Home infusion therapy, for cancer pain, 701
Homeopathic resonance, 1552
Homeopathy, 1554
Homeostasis
autonomic regulation of, 118
definition of, 419
pain and, 79
stress and, 419
Hooking maneuver, in slipping rib syndrome, 1189
Hoover, Katherine, 194
Hoover v Agency for Health Care Administration, 194–195
Hope, 77, 162, 167
Hopkins Opioid Program, 829
Hormonal therapy
for cancer pain, 747, 782

5637
 for chronic pelvic pain, female, 1085, 1086t
for dysmenorrhea, 1083–1084
for endometriosis, 1086t, 1087
for prostate pain syndrome, 1104
Hormones
and gender differences in pain, 94, 140
and opioid analgesics, 1338
and pregnancy, 944
Horner syndrome, 653, 859, 1182
Hospice, 1732, 1733f
Hospice Quality of Life Index, 1734
Hospital Anxiety and Depression Questionnaire (HAD), 1051, 1304
Hospital Anxiety and Depression Scale (HADS), 322, 402, 630, 631t
Hostility, 81–82, 1395–1396
How Doctors Think (Groopman), 1717
How We Die (Nuland), 152
HPA. See Hypothalamic-pituitary-adrenocortical (HPA) axis
HPV. See Human papillomavirus
H-reflex studies, 245
HSV. See Herpes simplex virus
HUG trials, of hydroxyurea, 976
Hull, Clark, 1421
Human immunodeficiency virus. See HIV/AIDS
Human papillomavirus (HPV), in HIV/AIDS, 987
Humeroacromial interface, 1150
Humors, 1, 1t, 1492, 1492t
Hurd, E. P., 1109
Hurt v. harm, 1408
Hurwitz, William, 200–201
Hyaluronic acid, for osteoarthritis, 490
Hyaluronidase, 1736
Hydralazine, for noncardiac chest pain, 1052
Hydrocodone, 1334t, 1345
abuse-deterrent formulations of, 1349t
for cancer pain, 690t, 695

5638
 dose conversions of, 829t
in emergency department, 1775, 1776t
extended-release, 690t, 695
for HIV pain, 994t
renal dysfunction and, 688t
urine testing for, 1016f
Hydrocortisone, epidural injections of, 1611
Hydromorphone, 1334t, 1344
for acute pain
continuous epidural, 833t, 834
intravenous patient-controlled, 832t
single-dose neuraxial, 833t
for burn pain, 903
for cancer pain, 690t, 691–692, 698–699, 821–822
for cancer pain in children, 798
for children, 813, 814t, 821–822
consumption trends for, 208–215, 209f, 211f–214f
dose conversions of, 829t
epidural, for children, 819, 819t
extended-release, 690t
hepatic dysfunction and, 689t
for HIV pain, 994t
in intensive care unit, 1786
intrathecal, 714–715, 714t, 1375, 1625, 1625t
trial of, 1631t
metabolites of, 1347t
morphine equivalence of, 208
myoclonus with, 1737
for neuropathic pain, 1366–1367, 1366t, 1375
parenteral, 698–699
rectal, 1342t
renal dysfunction and, 688t
subcutaneous, 1736
urine testing for, 1016f, 1509t
Hydrophilic local anesthetics, 1383

5639
Hydrophilic opioids, 833, 834, 853, 931
Hydrotherapy, for childbirth pain, 945
Hydroxychloroquine
for livedoid vasculitis, 548
for psoriatic arthritis, 496
for rheumatoid arthritis, 492, 492t
5-Hydroxytryptamine. See Serotonin
Hydroxyurea, in sickle cell disease, 955, 969, 971–972, 975–977, 976t
Hydroxyzine, for anxiety, 441
Hyoid bone, 1139f, 1163
Hyoscyamine, for nausea/vomiting in cancer patients, 684t
Hyperalgesia, 13, 45–47, 58–60
central pain and, 398, 399
complex regional pain syndrome and, 343
definition of, 58
diffuse, 525, 529
dorsal horn and, 107
inhibitory systems in, 58–59
male pelvic pain and, 1102
neck pain and, 1163
neuropathy and, 330
opioid-induced, 59–60, 1339
in cancer pain management, 690–691
in chronic pain patients, 460
clinical evidence of, 458–460
ethics of opioid cessation in, 1745–1747
genetics and, 460
in healthy controls, 459–460
in intrathecal drug delivery, 1626
in maintenance programs, 458–459
mechanisms of, 457–458, 458f
in opioid use disorder, 454, 457–460
in surgical patients, 459
and tolerance, 457
withdrawal, 457

5640
 postherpetic neuralgia and, 1186
primary, 58
secondary, 58
secondary somatic, 753
sensory testing for, 235–236
sickness response and, 420
spinal cord injury and, 585
stress-induced, 59
Hyperalgesic priming, 33
Hyperbaric oxygen therapy
for complex regional pain syndrome, 355
for livedoid vasculitis, 548
Hyperesthesia, 13
Hypermobility, in children, 915
Hyperpathia, 13, 235, 397
Hypersensitive xiphoid, 1190, 1199t
Hypersensitivity, 1765
clinical, triggers of, 58–60
etiologies of, 58
inflammation-induced, 58–59
NSAIDs and, 1326–1327
Hyperstimulation (noxious-level stimulation), 1527
Hypertensive lower esophageal sphincter, 1038, 1038f
Hyperthermia, maternal, neuraxial analgesia and, 949
Hypertonic dextrose, intradiscal, 1649
Hypertrophic cardiomyopathy, 1193t
Hypertrophic pulmonary osteoarthropathy (HPO), 634
Hypnic headache, 1026, 1026t, 1028–1029, 1134
Hypnosis, 1421–1438
for abdominal pain, 1070
for burn pain, 905, 1429
for cancer pain, 800, 1431
central mechanisms of, 1423–1424
for childbirth pain, 946
for children, 800, 1429–1430

5641
 for chronic pain management, 1434–1435
cognitive-behavioral therapy v., 1425–1426, 1431
for complex regional pain syndrome, 1423–1424, 1428
current research and applications, 1425–1431, 1425t
defining, 1422–1423
for dentistry, 1429
efficacy and effectiveness of, 1426–1427, 1434
for headache, 1430–1431
high and low hypnotizability in, 1423
history of, 1421–1422
for HIV pain, 997
induction procedures in, 1432–1433
for irritable bowel syndrome, 1430
medical techniques of, 1431–1434
for noncardiac chest pain, 1055, 1055f
for osteoarthritis, 1431
pain plasticity in, 1424
perioperative and procedural uses of, 1427–1428
for phantom limb pain, 1428
principles of preparation, induction, and suggestion in, 1431–1432
suggestions and imagery for, 1433–1434
testing hypnotizability for, 1424–1425
Hypnotic analgesia, 1423–1424
Hypnotic Induction Profile (HIP), 1425
Hypnotic State Assessment Questionnaire (HSAQ), 1425
Hypnotic states, 1422–1423
Hypoalgesia, 13
Hypochondriasis (somatization), 299, 446, 447–448, 448t, 525
chest pain in, 1202t
definition of, 13
spinal surgery in patients with, 1300–1301
Hypoglossal nerve, 1162t
Hypophysectomy, for cancer pain, 760
Hyposalivation, in cancer, 738–739
Hypotension

5642
 intracranial, 257–258, 258f
neuraxial analgesia in childbirth and, 949
Hypotensive lower esophageal sphincter, 1038
Hypothalamic-pituitary-adrenocortical (HPA) axis
in abdominal pain, 1067
in acute pain, 826
dysfunction of, 79
in fibromyalgia, 531
in noxious signaling and emotion, 413–414, 416–417, 416f
in sickness response, 420
in stress, 419
in stress-induced analgesia and hyperalgesia, 59
Hypothalamus, 62, 62f, 64–65, 108
in emotion and noxious signaling, 412, 413–416, 414f, 416f
magnocellular secretory cells of, 64
in nociceptive modulation, 55, 55t, 56–57, 56f, 64–65
opioid analgesics and, 1338
in pain–ANS interaction, 114
parvocellular secretory cells of, 64
projection pathways to, 45
in stress, 419
in stress-induced analgesia and hyperalgesia, 59
Hypothyroidism, 1168
Hypotonia, 234
Hypouricemic medications, 500
Hypoxemia, childbirth pain and, 942, 942f
Hypoxia, myofascial trigger points and, 508
Hysteria, 1–2, 437
HZO. See Herpes zoster ophthalmicus

I
IAHPC. See International Association for Hospice and Palliative Care
IASP. See International Association for the Study of Pain
Iatrogenic addiction, 1002, 1002t
Iberogast, for abdominal pain, 1072
IBS. See Irritable bowel syndrome

5643
Ibufenac, 1315
Ibuprofen, 1316t, 1321
for acute pain, 829–830
for cancer pain in children, 798
central nervous system effects of, 1328
for children, 811, 812t, 922
for elderly patients, 932
in emergency department, 1775, 1776t
gender differences in response to, 94
for HIV pain, 993, 994t
injectable, 1318, 1321
for migraine, 991t, 1024, 1024t, 1133
for neuropathic pain, 1369
for osteoarthritis, 490
relative efficacy of, 829t
topical, 1319t
Ibuprofen/famotidine, 1324
ICB. See Infraclavicular block
ICD-10. See International Classification of Diseases 10th Revision
ICD-11. See International Classification of Diseases 11th Revision
ICF. See International Classification of Functioning, Disability, and Health
ICHD. See International Classification of Headache Disorders
ICPRPs. See Interdisciplinary chronic pain and rehabilitation programs
ICU. See Intensive care unit
ID-Pain questionnaire, 396
IEQ. See Injustice Experience Questionnaire
IFC. See Interferential current
Ignatius Loyola (saint), 1
IHS. See International Headache Society
IIEF. See International Index of Erectile Function
Iliohypogastric block, 856
Iliohypogastric nerve, 854, 868–869, 869f
anatomy of, 1205, 1206f
in pelvic pain, 1090, 1102
Ilioinguinal block, 856, 856f

5644
Ilioinguinal nerve
anatomy of, 854, 868–869, 869f, 1205, 1206f
in pelvic pain, 1090, 1102
Illness anxiety, 299
Illness anxiety disorder, 446, 447–448, 448t
Illness Behavior Questionnaire, 447
Illness behaviors, 80, 445–446
Illness/injury sensitivity, 77
Image-guided tumor ablation, 711t
Imagery
for burn pain, 904
for central pain, 403
for children with chronic pain, 916
for complex regional pain syndrome, 350–351, 353
graded motor, 350–351, 368, 1497, 1531–1532
guided, 1407
for hypnosis, 1432–1434
for phantom pain, 368
for sickle cell disease pain, 973
Imaging of pain. See Diagnostic imaging of pain; Functional imaging of
pain
Imipramine
in biologic tests for depression, 435
for central pain, 400
for chest pain in panic disorder, 442
for neuropathic pain, 400, 1359–1361, 1360t, 1361t
for noncardiac chest pain, 1052–1053
Immediate-release opioids, 1342
Immersive virtual reality, for phantom pain, 368
Immobilization, in complex regional pain syndrome, 345, 350
IMMPACT. See Initiative on Methods, Measurement, and Pain
Assessment in Clinical Trials
Immune reconstitution inflammatory syndrome, 989
Immune system, 419–420
Immune-mediated neuropathy, in HIV/AIDS, 988t

5645
Immunoassay drug tests, 1016
Immunotherapy, for cancer, 779
Impaired glucose tolerance, 331, 335
Impairment, 302
association with disability, 303
definition of, 13, 302, 1492
pain rehabilitation and, 1492
permanent, AMA guide to, 311
Impingement syndromes, shoulder and pectoral girdle, 1150, 1155f, 1157
Implantable peripheral nerve devices. See Peripheral nerve stimulation
Implantable pulse generator, 1559
Implantable pumps, 712–713, 712f, 1632–1634. See also Intrathecal drug
delivery
Implantable spinal devices, 1277. See also Intrathecal drug delivery;
Spinal cord stimulation
psychological screening of candidates for, 1298–1309
Implementation intentions, 1476–1477, 1477t
Implosive therapy, 444
Importance, feeling of, 479–480, 479t
Importance and confidence scales, 1729
IMRT. See Intensity-modulated radiation therapy (IMRT), for head and
neck cancer
In vitro fertilization (IVF), complications of, 1082–1083
INCB. See International Narcotics Control Board
Incentive spirometry, for acute chest syndrome, 965
Incident pain, 644
Indian medicine (Ayurveda), 1554
Individual differences in pain, 90–102
biopsychosocial model of, 90–91, 91f
challenge of studying, 90
ethnicity/race and, 94–96, 139–141
genetic contributions to, 96–97
interaction among, 97
observational learning and, 428
quantifiable and controllable stimuli for, 90

5646
 sex/gender and, 91–94, 140–141
treatment outcomes in, 90, 1312
Indomethacin, 1316t, 1320
for children, 811
for elderly patients, 932
for gout, 500
for hemicrania continua, 1029
history of, 1315
for hypnic headache, 1134
for paroxysmal hemicrania, 1027
for primary cough headache, 1028
for primary exertional headache, 1028
for primary sex headache, 1028
for primary stabbing headache, 1028
Induction, in hypnosis, 1431–1433
Inductive empirically based classifications, 21–22
Industrial Insurance Medical Advisory Committee, Washington State, 309
Ineffective treatment, patient improvement in, 123–124, 124t
Infants and neonates
analgesic pharmacology in, 810–818
cancer pain in, 788
epidural analgesia for, 818–819
increased awareness and treatment of, 809, 809t
nociception in, 809
opioid analgesic effects in, 1341
pain assessment in, 809–810
Infectious arthritis, 500–501
Infectious complications, 715, 1635, 1760–1761
Inferior cervical ganglion, 112, 113f
Inferior glenohumeral ligament, 1157, 1157f
Inferior gluteal nerve, 1205
Inferior mesenteric ganglion, 113f
Infiltration anesthesia, 1386
Inflammation
in complex regional pain syndrome, 342

5647
 in sickle cell disease, 958
of skin, 543, 554–558
Inflammation-induced hypersensitivity, 58–59
Inflammatory bowel disease, arthritis associated with, 496–497
Inflammatory demyelinating polyneuropathy, in HIV/AIDS, 988–989
Inflammatory masses, intrathecal, 715, 1638–1639, 1639f
Inflammatory mediators, in myofascial pain (trigger points), 511
Inflammatory myopathies, in HIV/AIDS, 989
Inflammatory visceral pain, 751–752
Infliximab
for Dercum disease (adiposis dolorosa), 554
for pyoderma gangrenosum, 552
for rheumatoid arthritis, 492–493, 492t
Informed consent
in end-of-life care, 160
in pain medicine, 1007
Infraclavicular block (ICB), 859–861
for children, 820
clinical effects of, 860–861
indications for, 859
landmarks for, 860, 860f
technique for, 860, 860f
Infraorbital neuralgia, 1122–1123
Infrared radiation, therapeutic, 1525
Infundibulum, 62f
Ingber, Donald E., 1552
Inglis, Brian, 1546
Ingrown toenail, 1226, 1226f
Inguinal pain, peripheral neurectomy for, 1670
Inhalational analgesia, for childbirth pain, 946
Inhibition, of neurons, 42–43
Inhibitory amino acids, 48
Inhibitory systems, in hyperalgesia, 58–59
Initial visit questionnaire, 236–240
Initiative on Methods, Measurement, and Pain Assessment in Clinical

5648
 Trials (IMMPACT), 129, 349, 467
Injury, in civil litigation, 193
Injustice Experience Questionnaire (IEQ), 230
Inmates, cancer pain in, 601–602
Inpatient pain services, 843
Insomnia. See also Sleep disorders
in cancer patients, 632–633
Insomnia Severity Index, 633, 633t
Inspection, 1483
low back, 1264
Institute of Medicine (IOM)
on complementary medicine, 1548
on noncancer pain management, 676
on opioid pain management, 173, 185
on prevalence of pain, 172
Relieving Pain in America, 153, 185, 296, 1793
Insula, 65, 66f, 67, 108
in depression–pain association, 436
in emotion and pain, 412, 417
in pain processing, 67, 68f
in pain–ANS interaction, 114
Integrated trigger point hypothesis, 504–506, 510–511
Integrative health, 1547, 1547t. See also Complementary and integrative
health
Integrative medicine, 1547t. See also Complementary and integrative
health
Intensity- and functioning-based classification, 16–17
Intensity coding, in visceral pain, 1065
Intensity of pain, 566
assessment of, 274–276, 282f, 321, 1303t, 1304, 1771–1772
in cancer, 636, 664
in central pain states, 397–398, 398t
in childhood cancer, 790, 791
evaluation of, 228–229, 228f
low back, 1250, 1262–1263

5649
 in neck and arm, 1160
in spine surgery candidates, 1303t, 1304
Intensity theory, 6
Intensity-modulated radiation therapy (IMRT), for head and neck cancer,
736, 737
Intensive care unit (ICU)
adjuvant therapy in, 1786–1787
analgesics in, 1784–1787
analgosedation in, 1782, 1788–1789
comprehensive bundled care i, 1789, 1789t
end-of-life care in, 1734, 1789, 1789t
integrated analgesia management in, 1788–1789
nonpharmacologic modalities in, 1787
nonverbal patients in, 1734, 1734t
opioids in, 1782, 1784, 1785–1786
pain evaluation and monitoring in, 1783–1784, 1784t
pain management in, 1782–1792
regional anesthetic approaches in, 1787–1788
SCCM recommendations for, 1783, 1783t
systemic and physiologic consequences of pain in, 1783, 1783t
Intention-to-treat analysis, 128
Interclavicular ligament, 1150
Intercostal nerve(s), 721, 854, 1181–1182, 1184f
Intercostal nerve block, 1607
for acute pain, 837
adverse effects of, 721
for cancer pain, 711t, 721–722, 722f
general considerations in, 721
indications for, 721
for intercostal neuralgia, 1186, 1186f
outcome studies of, 722
for postsurgical breast pain, 1190–1191
for rib fracture pain, 1188, 1189
technique of, 721, 721f, 722f
Intercostal neuralgia, 1186, 1197t

5650
Intercostal pain, peripheral neurectomy for, 1670
Intercostal spaces, 1181, 1183f
Intercostobrachial nerve, 1147, 1151f
Intercostobrachial pain, peripheral neurectomy for, 1670
Interdigital (Morton’s) neuroma, 1224–1225, 1225f, 1670–1671
Interdisciplinary approach
biopsychosocial model of, 1711
in chronic pain management, 1709–1716
cost-effectiveness of, 1710
empirical support for, 1709–1710
follow-up in, 1713–1714
future considerations for, 1715
history of, 1709
multidisciplinary approach v., 1709, 1710–1711
patient as active participant in, 1709
process of, 1713–1714
referral for, 1713
team composition and roles in, 1711–1713
theoretical basis for, 1710–1711
VA health system as model of, 1714–1715
cognitive-behavioral therapy in, 1411
multidisciplinary approach v., 1709, 1710–1711
in rehabilitation, 1493, 1494–1495, 1494f
Interdisciplinary chronic pain and rehabilitation programs (ICPRPs), 1421
Interdisciplinary (multidisciplinary) pain center, 14, 324, 1494
Interdisciplinary pain rehabilitation programs (IPRPs), 85–86
Interference. See Pain interference
Interferential current (IFC), 1527–1528
Interferon-γ, 420, 458
Interlaminar epidural steroid injections, 1611, 1613–1615
adverse events in, 1615
evidence on, 1615
nonimage-guided v. image-guided, 1615
technique of, 1613–1614, 1614f
Interleukin 1 (IL-1), 420, 485, 627, 733, 960

5651
Interleukin 1 beta (IL-1β), 49, 420, 458, 512–513, 628, 732
Interleukin 1 (IL-1) inhibitor, 497, 500
Interleukin 3 (IL-3), 1039
Interleukin 4 (IL-4), 511
Interleukin 5 (IL-5), 1039
Interleukin 6 (IL-6), 49, 342, 420, 511–513, 627, 628, 733
Interleukin 6 (IL-6) inhibitors, 492t, 493
Interleukin 8 (IL-8), 420, 512–513, 531
Interleukin 10 (IL-10), 511
Interleukin 12 (IL-12), 458
Intermediate cervical ganglion, 112
Intermittent claudication, 567–569, 567f
Intermittent intravenous bolus dosing, for children, 815
Intermittent pain, assessment of, 281, 284f, 286
Internal derangement, in TMJ disorders, 1131–1132, 1132f, 1133t
Internal disk disruption, 1644–1645, 1645f
International access, to therapeutic opioids, 205–224
adequate availability in, 206–207
barriers to, 215–221, 216t
disparities in consumption, 207–209, 208t
essential medicines and controlled substances in, 206
improving, 220–221
trends in consumption, 208–215, 209f, 211f–214f
UN recommendations on, 219–220
International Association for Hospice and Palliative Care (IAHPC), 206,
208, 218, 220
International Association for the Study of Pain (IASP), 1751
on cervicogenic headache, 1171
Classification of Chronic Pain, 1265
classification system of, 18–20, 19t, 20t, 22
coding system of, 19–20, 19t, 20t
criteria for complex regional pain syndrome, 341, 341t, 346
definition of neuropathic pain, 626
definition of pain, 410, 566
definition of pain as emotional experience, 79

5652
 definitions and terminology of, 11–15, 141
on emotion and pain, 410
founding of, 8, 9
global year against cancer pain, 676
INCB recommendations for, 219
levels of pain programs, 1494
on low back pain, 1245–1246, 1259, 1261, 1265
on neck pain, 1230
Neuropathic Pain Special Interest Group, 400, 1374
on pain reporting, 143
on pelvic pain, 1098
on psychology of pain, 138, 141
on right to pain relief, 158
International Classification of Diseases 10th Revision (ICD-10), 15
criteria for trigeminal neuralgia, 1111–1112, 1111t
International Classification of Diseases 11th Revision (ICD-11), 11, 15, 20
International Classification of Functioning, Disability, and Health (ICF),
16, 1492, 1493f
International Classification of Headache Disorders (ICHD), 20, 1019,
1108, 1133
International Continence Society, 1098
International Headache Society (IHS), 1021, 1025, 1027, 1029, 1031
criteria for cervicogenic headache, 1171, 1171t, 1236, 1236t
criteria for head, face, and neck pain disorders, 1128, 1128t
criteria for trigeminal neuralgia, 1111–1112, 1111t, 1691, 1691t
International Index of Erectile Function (IIEF), 1103
International Narcotics Control Board (INCB), 174, 206–208, 215, 216t,
219–220
International Pain Policy Fellowship (IPPF), 220–221, 221t
International Society for the Study of Vulvovaginal Disease (ISSVD),
1092
International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS), 581t,
583t
International Spinal Cord Injury Pain (ISCIP) Classification, 581–582,
581t

5653
International Standards for the Neurological Classification of SCI, 581
International treaties, on drug control and medical use, 173–175, 206–208
Internet-delivered CBT, 1442
Interneurons
connectivity of, 43
neurotransmitters from, 48–49
Interoception, 412, 412f
Interpersonally distressed patients, 18
Interpleural analgesia, for cancer pain, 759
Interprofessional pain programs, 1411. See also Interdisciplinary approach
Interscalene block (ISB), 857–858
clinical effects of, 858
indications for, 857
landmarks for, 857
nerve stimulation for, 857
ultrasound guidance for, 857–858, 857f, 858f
Interspinous ligaments, 1141, 1142f
Interstate and Foreign Commerce Committee, 178–179
Interstitial cystitis, pelvic pain in, 1088–1089
Interventional pain therapies, 1794. See also specific therapies
for cancer pain, 711–731, 711t
evidence-based, 1757–1758
training and credentialing in, 1755–1756
Intervertebral disks. See Disk(s)
Intervertebral foramina, 1141, 1143–1145, 1144f
Interviews
motivational, 462, 1512
psychological, 319–320, 320t
Intestinal obstruction, chronic, 755
Intestinal pain, adjuvant analgesics for, 686
Intoxication, 1508
Intra-articular analgesia, for acute pain, 837
Intra-articular blocks, 1600, 1605–1606, 1606f. See also specific joints
Intracerebroventricular opioids, for cancer pain, 699
Intracranial hypertension, 258

5654
Intracranial hypotension, 257–258, 258f
Intracranial lesions, neck pain with, 1233
Intractable keratosis, 1223
Intractable pain
approaches to controlling, 1668
at end of life, 1736–1739
peripheral nervous system stimulation for, 1558
Intractable pain treatment acts (IPTAs), 180, 184, 194, 1723–1724
Intradermal water injections, for childbirth pain, 945–946, 945f
Intradiscal electrothermal therapy, 1647
Intradiscal therapies, 1274, 1278, 1643–1652
ablation, 1646–1647
antibiotic, 1649
biacuplasty, 1647–1648, 1648f
biologics, 1649–1650
chemical, 1648–1649
etanercept, 1649
methylene blue, 1649
percutaneous RF thermocoagulation, 1647–1648
proliferants, 1649
stem cell, 1274, 1650
Intralesional injections, for cancer-related bone pain, 747–748
Intramuscular NSAIDs, 1318
Intramuscular opioids, 828–829
Intranasal fentanyl, 693t, 694
Intranasal NSAIDs, 1318
Intranuclear radiofrequency, 1647
Intraperitoneal chemotherapy pain, 755
Intraspinal pathways, 43
Intrathecal drug delivery, 1299, 1343, 1385, 1623–1642
for acute pain, 833, 851–852
baclofen, 714t, 715, 1624, 1625t, 1627, 1631t, 1639
complications of, 1764
for neuropathic pain, 1375
for spinal cord injury, 590

5655
basic pharmacology of, 1623, 1623f
for cancer pain, 711–716, 711t, 714t, 1639–1640
indications for, 712
outcome studies of, 713–714
pharmacology in, 714–715, 714t
risk management in, 715
catheters for, 712
for central pain, 403
for childbirth pain, 948–949
for chronic noncancer pain, 1640, 1640t
clonidine, 714t, 715, 852, 1625t, 1626–1627
for neuropathic pain, 1375
for spinal cord injury pain, 592
trial of, 1631t
withdrawal in, 1639
common diagnoses treated with, 1629, 1629t
complications of, 715, 1634–1639, 1634t, 1764
catheter-related, 715, 1634t, 1636
device-related, 715, 1634t, 1636–1637
infectious, 715, 1635
pharmacologic, 715, 1634t, 1637–1639
surgical, 1634–1636, 1634t
contraindications to, 715, 1630
cost of, 713, 713t, 1630
drug withdrawal in, 1639
for end-of-life pain, 1736
epidural v., 713, 1631, 1631t
history of, 1623
implantable pumps for, 712–713, 712f, 1632–1634
constant flow, 1632, 1632t
factors affecting, 1632, 1632t
fully programmable, 1632
implantation technique for, 1632–1634, 1633f
problems with, 1636–1637
refill-related complications of, 1634t, 1636–1637

5656
 implantable v. exteriorized, 713, 713t
inflammatory masses (granuloma) in, 715, 1638–1639, 1639f
local anesthetic, 714t, 715, 1625t, 1626
for neuropathic pain, 403, 1375
opioid, 714–715, 714t, 1343, 1624–1625, 1624f, 1625t, 1637–1640
for acute pain, 851–852
dose and concentration limitations for, 1638, 1638t
in end-of-life care, 1736
for neuropathic pain, 1375
side effects of, 1637
for spinal cord injury pain, 592
tolerance in, 1637–1638
PACC recommendations for, 1624, 1625t, 1632
patient outcomes in, 1639–1640
patient selection for, 1629–1630
patient-controlled, 714
for postherpetic neuralgia, 1118
psychological screening for, 1298–1299
selection of agents for, 1624
for spinal cord injury pain, 592–593
trialing techniques for, 1630–1632, 1631t
unintended, 1763
Intrathecal drug delivery system (IDDS), 1623
Intrauterine contraceptive device, and PID, 1080
Intravenous drug delivery
in end-of-life pain, 1736
of NSAIDs, 1318
of opioids, 1736
for acute pain, 828–829
for burn pain, 901–902
for cancer pain, 698–699
Intravenous immunoglobulin
for bullous pemphigoid, 558
for calcinosis cutis, 549
for epidermolysis bullosa, 558

5657
 for leukocytoclastic vasculitis, 546
for livedoid vasculitis, 548
for Stevens-Johnson/TEN syndrome, 557
Intravenous patient-controlled analgesia (IVPCA). See also Patient-
controlled analgesia
for acute pain, 832–833, 832t
for childbirth pain, 946
Intravenous regional anesthesia (IVRA), 354, 1386
Intravenous regional block (IRB), 1683–1684
Intraventricular administration, 1343
Intravesical chemotherapy, 755–756
Intrinsic cardiac nervous system, 1576
Inventory of Negative Thoughts in Response to Pain (INTRP), 1305
Investigational new drug (IND), 1313
Investigations, history of, 232
Ionotropic receptor/channels, 45–47
Iontophoresis, 1528–1529
Iowa Pain Thermometer, 930
IPPF. See International Pain Policy Fellowship
IPRPs. See Interdisciplinary pain rehabilitation programs
IPTAs. See Intractable pain treatment acts
IRB. See Intravenous regional block
Ireland
pain medicine in, 1755
topical NSAIDs in, 1319t
Iritis, in ankylosing spondylitis, 494
Ironic processes theory of mental control, 1396–1397, 1396t
Irons, Ernest E., 955
Irritable bowel syndrome (IBS)
adverse life events/stress and, 1067
antidepressants for, 1070
biomarkers of, 1068
blocking afferent pathways in, 1070–1071
in children, 911, 923
complementary and integrative health in, 1072

5658
 esophageal sensory testing in, 1050
in fibromyalgia, 525, 526, 527, 534
functional chest pain with, 1034
genetic factors in, 1066–1067
group therapy for, 1447t, 1449t, 1463
hypnosis for, 1430
lifestyle modifications for, 1068–1069
microbial colonization in, 1067–1068, 1071
microbiome alteration for, 1071
neuromodulators for, 1069–1070
nonopioid analgesics for, 1069
opioid analgesics for, 1069
patient–provider relationship in, 1069
pelvic pain in, 1088
placebo response in, 1069
psychological factors in, 442, 1067, 1067f
psychological interventions for, 1070
sensitization and hypersensitivity in, 1066
sleep patterns in, 1068
smooth muscle relaxants for, 1071
susceptibility factors in, 1066–1068
treatment of, 1068–1072
IRT. See Item response theory
ISB. See Interscalene block
Ischemic necrosis. See Avascular necrosis
Ischemic pain
spinal cord stimulation for, 1575–1576, 1575f, 1578
visceral, 751–752
Ischemic (arterial) ulcers, 550, 569–570
ISCIPBDS. See International Spinal Cord Injury Pain Basic Data Set
Islet cells, 41
Isometric exercise, 1497–1498, 1498t
Isoniazid, and pyridoxine deficiency, 331–332
Isotonic exercise, 1498t
Israel, topical NSAIDs in, 1319t

5659
ISSVD. See International Society for the Study of Vulvovaginal Disease
Itching. See Pruritus
Item response theory (IRT), 227, 287
IVF complications, 1082–1083
IVPCA. See Intravenous patient-controlled analgesia
IVR. See Immersive virtual reality
IVRA. See Intravenous regional anesthesia

J
Jackson’s compression test, 1166
Jacobson, Edmund, 1407
Jamar hand dynamometer, 1503
James, Henry, 196
Janet, Pierre, 1421
Jannetta, Peter, 1110
Janus kinase (JAK) inhibitor, for rheumatoid arthritis, 492t, 493
Japan, patient pain in, 142
John Hopkins Center for Health Disparities Solutions, 172
Johrei therapy, 1055
Joint(s)
anatomy of, 484–485, 484f
chest wall, 1181
nerve and blood supply of, 485
testing of, 233
Joint (synovial) fluid, 484, 484f, 486–487, 486t
Joint pain. See also Arthritis; specific joints
in children, 909–910
clinical approach to, 485–487
fibromyalgia-type, 485
history of, 485
inflammatory, 485
mechanical, 485–486
number of joints affected in, 485–486, 486t
pattern recognition in, 486
physical examination in, 486
synovial fluid examination in, 486–487, 486t

5660
Joint replacement, 490, 493, 495
Joint United Nations Programme on HIV/AIDS (UNAIDS), 205
Joints of Luschka, 489, 1138, 1140t, 1141f, 1144f
Jugular foramen syndrome, 653
Jurjani, 1109
Justice, 151, 1744
Juvenile rheumatoid arthritis, 811, 909, 917

K
Kabat-Zinn, Jon, 1407
Kainate antagonists, for cancer pain, 757–758
Kainate (KA) receptors, 45–47, 46t
Kaltenborn, F., 1497, 1497t
Kansas, criminal litigation over pain management in, 198–199, 201
κ-Opioid receptor (KOR), 48, 1333
Karnofsky performance status (KPS), in cancer-related bone pain, 648–
649, 650t, 769–770, 769f
Keen, William W., Jr., 9
Kentucky, oxycodone litigation in, 199
Kepivance, for oral mucositis prevention, 740
Keratinocyte growth factor, for oral mucositis prevention, 741, 796
Keratosis, intractable, 1223
Kerr, T. N., 1110
Ketamine
for acute pain, 830
for bone pain in cancer, 747
for burn pain, 902–903
for cancer pain, 685, 757, 822
for cancer pain in children, 794
for central pain, 403
for children, 811–812, 812t, 822
for complex regional pain syndrome, 353
in emergency department, 1778
for end-of-life pain, 1737–1738
epidural, for acute pain, 834
for erythromelalgia, 559

5661
 in intensive care unit, 1786–1787
intranasal, 1776–1777
intrathecal, 714t, 715, 1627
for neuropathic pain, 403, 1367, 1368t
in opioid-sparing strategy, 1340
for patients with substance use disorder, 463
for phantom pain, 366, 795
for postherpetic neuralgia, 388
for spinal cord injury pain, 591–592
topical
as adjuvant analgesic, 685
for neuropathic pain, 1369, 1370t
Ketoprofen, 685, 1316t, 1319t, 1321
Ketorolac, 1316t, 1320–1321
for acute pain, 830
for children, 811, 812t
for elderly patients, 932
in emergency department, 1775, 1776–1777, 1776t
injectable, 1318, 1320–1321
in intensive care unit, 1787
intranasal, 1318, 1776–1777
intrathecal, 715, 1629
oral, 1320
relative efficacy of, 829t
Ki, 1552, 1555
Kidney(s)
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Kidney cancer, 637, 642
Kidney disease
chronic
NSAIDs and, 1327–1328
stages of, 1328t
comorbid with cancer, 601
Kidney failure. See Renal failure

5662
Kinesophobia, 226, 227, 229, 230
Kinetic chain
closed, 1498t
open, 1498t
Kinetic chain theory, 1480–1481
Klein, Gerald, 199
Kleinman, Arthur, 155
Klüver-Bucy syndrome, 70
Koller, Carl, 8, 1382
Kölliker-Fuse nucleus, 56
KOR. See κ-opioid receptor
KPS. See Karnofsky performance status
Krause, Elliott A., 144
Kyphoplasty, 725–727, 726f, 748

L
Labat approach, to sciatic nerve, 878, 878f
Labeled line theory, 543, 1698
Labeling, drug, 175
Labor
nonobstetric drug therapy during, 951–952
pain during (See Obstetric pain)
Labor support, 945
Lacosamide, for neuropathic pain, 1363t, 1366
Lacrimal gland
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Lactation
analgesic drugs during, 952
drug classifications during, 951–952
drug therapy during, 951–952, 951t
Laminae. See Spinal laminae
Lamotrigine
for acute pain, 830–831
for central pain, 401t, 402
for HIV pain, 994t, 996

5663
 for neuropathic pain, 402, 1363t–1364t, 1365
for painful neuropathies, 337
for spinal cord injury pain, 590, 591
and Stevens-Johnson/TEN syndrome, 556
for trigeminal neuralgia, 1114–1115, 1691
for vulvodynia, 1092
Langley, J. N., 110
Lansoprazole, for proton pump inhibitor test, 1044
LANSS. See Leeds Assessment of Neuropathic Symptoms and Signs
Laparoscopic fundoplication, 1054–1055
Laparoscopy, diagnostic, in female pelvic pain, 1085
Large arteries
innervation of, 566
pain in, 569
Larynx, sympathetic and nociceptive nerve supply to, 115t
LASBs. See Local anesthetic sympathetic ganglion blocks
Lasègue’s sign or test, 653, 1217
Laser therapy, 1524–1525, 1553
classification of lasers for, 1524
for myofascial pain, 518, 1524–1525
for oral mucositis prevention and treatment, 737, 741, 796
Laser-evoked potential (LEP) test, 71
Lasmiditan, for migraine, 1024
Latency, in nerve conduction studies, 244
Lateral atlantoaxial joint block, 1605–1606, 1606f
Lateral cord, of brachial plexus, 1147
Lateral corticospinal tract, 40f
Lateral femoral cutaneous nerve (LFCN), 868–869, 869f
anatomy of, 876, 1205, 1206f, 1208, 1209f
in implantation of peripheral nerve device, 1562f, 1563
in pelvic pain, 1102
Lateral femoral cutaneous nerve block, 876, 1211
clinical effects of, 876
indications for, 876
landmark technique for, 876

5664
 ultrasound guidance for, 876, 876f, 877f
Lateral femoral cutaneous nerve entrapment, 1208–1211, 1677
diagnosis of, 1210
epidemiology of, 1208–1210
etiology of, 1210
pelvic compression test in, 1210, 1210f
signs and symptoms of, 1210
treatment of, 1210–1211, 1670
Lateral pain system, 65
Lateral parvocellular zone, 63
Lateral reticular nucleus (LRN), 55, 56
Lateral reticulospinal tract, 40f
Lateral syndrome, 1170t
Lateral tegmentospinal tract, 40f
Laudanum, 8
Law and policies, affecting pain management, 172–192, 1313
additional U.S., considering, 185–186
balance principle in, 174, 181, 184, 187–188, 207, 207t, 1001
barriers to safe and effective opioid use, 172–173, 215–221, 216t
diversion considerations in, 186–187
future of pain medicine and, 1793–1794
international access to opioids, 205–224
international treaties, 173–175, 206–208
policies governing opioid use, 173
UN recommendations on, 219–220
unrelieved pain as public health problem, 172
U.S. federal law, 175–180
U.S. state laws, 180–185
Law of Specific Nerve Energies, 5, 6
Lawsuits. See Litigation, over pain management
Laxatives, for opioid-induced bowel dysfunction, 683, 1341
“Layer cake,” of pain dimensions, 226, 226f
L’DISQ, 1647
Leach, Ruth, 198–199
Learned helplessness, 415, 791

5665
 in burn patients, 905
Learned pain, 1202t
Learning, 425–429
classical conditioning, 425, 425f (See also Classical conditioning)
hippocampus in, 70
integrating principles in pain treatment, 428–429
major principles of, 425–426
observational (social), 83, 426, 428
operant conditioning, 425–426 (See also Operant conditioning)
Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), 278,
285, 396
Leflunomide
for psoriatic arthritis, 496
for rheumatoid arthritis, 492, 492t
Leg pain, in failed back surgery, 1293–1294
Leg ulcers, in sickle cell disease, 971–972, 971f, 971t, 972t
Legionella, in HIV/AIDS, 987
Legitimate medical purpose, 178
Leiomyoma, 560, 560f, 561t, 1082
Leksell, Lars, 1116
Lenalidomide, for complex regional pain syndrome, 352
Leptomeningeal carcinomatosis, 645t, 776
Leptomeningeal metastases, 654, 654t
Leriche, René, 9
Leriche syndrome, 567f
Leroux, Henri, 8
Lesser occipital nerve, 1146, 1146f
Lesser occipital nerve block, 1171
Lethal dose, in physician-assisted death, 169
Letrozole, 782, 1087
Leukemia, 622f, 643, 793
Leukocytoclastic vasculitis, 544t, 546, 546f
Leuprolide, for priapism, 969
Levamisole-contaminated cocaine, 549, 549f
Levator ani, in male pelvic pain, 1101

5666
Levetiracetam
for central pain, 401t
for migraine, 990t
for neuropathic pain, 1364t
for spinal cord injury pain, 591
for trigeminal neuralgia, 1114–1115
Levin, Stephen M., 1552
Levobupivacaine
for childbirth pain, 948
for trigger point injections, 516
Levofloxacin, for prostate pain syndrome, 1103
Levonorgestrel-releasing intrauterine system, 1084, 1086t, 1087
Levorphanol, 1334t, 1344–1345
for cancer pain, 692–693
dose conversions of, 692, 692t, 829t
metabolites of, 1347t
for neuropathic pain, 1366–1367, 1366t
Leyden jar, 1570
LFCN. See Lateral femoral cutaneous nerve
Lhermitte’s phenomenon, 398
Lhermitte’s sign, 1166
Libertarianism, and physician-assisted death, 169
Lidocaine, 1386t
for abdominal pain, 1070
for central pain, 403
for children, 817
for complex regional pain syndrome, 353
dosing in nerve blocks, 888t
injections
for myofascial pain, 516
for vagal neuralgia, 1122
intrarectal, for IBS, 1070
intrathecal, 715
intravenous, 1387–1388
for acute postoperative pain, 1387

5667
 for burn pain, 902, 903
for Dercum disease (adiposis dolorosa), 554
for end-of-life pain, 1737
for neuropathic pain, 1367, 1387–1388
for spinal cord injury pain, 591
molecular structure of, 1382, 1382f
for oral mucositis, 737
for painful neuropathies, 338
patch
for herpes zoster, 378
for neuropathic pain, 686t
for phantom pain, 365–366, 795
for residual limb pain, 368
systemic toxicity of, 1761–1763, 1763f
topical
as adjuvant analgesic, 685
for burn pain, 903
for cancer pain in children, 794
for manubriosternal arthritis, 1190
for myofascial pain, 1190
for neuropathic pain, 1367, 1369, 1370t
for postherpetic neuralgia, 384t, 387–388, 1118
for rib fracture pain, 1189
for trigeminal neuralgia, 1114–1115
Life story, in psychiatric illness, 431–432
Lifeworld, 139
Lifting protocols, 1502, 1503t
Ligamentous injuries, medical evaluation of, 315
Ligamentous stretch, in pregnancy, 1082
Ligamentum flavum, 1141, 1142, 1142f, 1144f
Ligamentum nuchae, 1141
Light therapy, 1524–1525
Light touch, 235
Likert scales, 736
Limb(s). See also Lower extremities; Upper extremities

5668
 sympathetic and nociceptive nerve supply to, 117t
Limb pain. See also Lower extremity pain; Upper extremity pain
diagnostic imaging in, 251, 262–268
peripheral nerve entrapment and, 267–268
phantom (See Phantom limb pain)
piriformis syndrome and, 267
thoracic outlet syndrome and, 267
Limbic system, 55–57, 62, 65, 67–70
in anger, 1394
in depression–pain association, 436, 436f
in neuroanatomy of emotion, 412, 412f, 414
Lipid emulsion, for local anesthetic toxicity, 888, 1388, 1388f
Lipid solubility
of local anesthetics, 1383
of opioid analgesics, 833, 834, 853, 931
Lipophilic local anesthetics, 1383
Lipophilic opioids, 833, 834, 853, 931
Liposomal local anesthetics, 1389
Liposomal morphine, 833
LIPUS. See Low-intensity pulsed ultrasound
Liquid chromatography/tandem mass spectroscopy (LC/MS-MS), 1015,
1016, 1017, 1509
Lisfranc joint instability, 1221
Lisinopril, for migraine prevention, 1023t
Lissauer’s tract, 39, 41, 107
Liston, Robert, 2
Lithium
for cluster headache, 1134
for hypnic headache, 1028, 1134
Litigation, over pain management, 193–204
administrative proceedings, 193–195
civil, 193, 195–198
constitutional cases, 201–202
criminal, 198–201
federal, 199–201

5669
 state and local, 198–199
fear of, as professional barrier to pain relief, 154, 216, 676, 1725–1726
lessons from, 203
Livedoid vasculitis, 545t, 548, 548f
Liver
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Liver cancer
epidemiology of, 622f
tumor encapsulation in, 637
visceral pain in, 653, 755
Liver disease/dysfunction
comorbid with cancer, 601
and local anesthetics, 1384
and NSAID therapy, 1318
and opioid therapy, 688–689, 689t
Liver injury, drug-induced, 986
Livingston, William K., 6
LLLT. See Low-level laser therapy
Local anesthetic(s), 1382–1391. See also Nerve blocks; specific
anesthetics
for abdominal pain, 1070
and acid–base balance, 1383
adverse effects of, 1388–1389
allergies to, 1388–1389, 1596
for burn pain, 902, 903
for childbirth pain, epidural, 947–948, 947t
for children, 817
chirality of, 1382–1383
dosing guidelines for nerve blocks, 888t
for epidural steroid injections, 1611
historical perspective on, 1382
intrathecal, 714t, 715, 1625t, 1626
lipid solubility of, 1383
mixtures of, 1387

5670
 molecular structure of, 1382, 1382f
pH adjustment of, 1386–1387
pharmacodynamics of, 1383, 1383f
pharmacokinetics of, 1383–1384
absorption, 1384, 1384f
biotransformation and excretion, 1384
disease states affecting, 1384
distribution, 1384
pharmacology of, 1383–1384
potency, onset, and duration of, 1386, 1386t
for pregnant patients, 1387
prolonged-duration, 1389
regional administration of, 1384–1387
differential blockade in, 1384–1385
systemic administration of, 1387–1388
toxicity of, 887–888, 1388, 1388f, 1761–1763, 1763f
for trigeminal neuralgia, 1115
unintended destinations following administration, 1763
vasoconstrictor effect of, 1387
Local anesthetic sympathetic ganglion blocks (LASBs), 1683, 1684
Location of pain, 316–317, 316f
in cancer, 663–664
Locke, John, 1109
Locus coeruleus
in acute pain, 827
in descending modulation of pain, 55, 55t, 56, 56f
in emotion, 414, 414f
in hyperalgesia, 58–59
in neuropathic pain, 59
in stress, 419
in vigilance network, 70
Loeser, John D.
on consciousness and pain, 144
general model of pain, 85
on interdisciplinary management, 1709

5671
 on pain medicine as new discipline, 137
on rehabilitation, 1490
training under, 1751
Logicoscientific knowledge, narrative v., 143
Loin pain, 1245–1246
Long, Crawford, 8
Long bone metastases, 645t
Long thoracic nerve, 1148f, 1153t
Long-acting local anesthetics, 1389
Long-acting (LA) opioids, 175–176, 689–690, 696, 1342
Longfellow, Fanny, 940
Longissimus capitis, 1141, 1143f
Longissimus cervicis, 1141, 1143f
Long-term memory, 1422
Long-term potentiation, 53
Longus colli tendonitis, 1233
Loperamide, 737, 1069
Lorazepam, 447, 1737, 1739t
Louisiana
addiction-related terminology in, 183t
administrative proceedings over pain management in, 194
Low back pain
acute, 1245–1258, 1539
activity/activation in, 1254–1255
aggravating factors in, 1250
alarming terminology in, 1253
ancillary investigations in, 1252–1253, 1252t
associated features in, 1251
causes of, 1246–1247
concern in, 1247, 1248f
distribution of, 1250
duration of illness, 1250
eight C’s in explaining, 1254, 1254t
extrinsic disorders and, 1246–1247
fear in, 1251, 1255–1256

5672
formulation of assessment in, 1253
imperatives for practitioners, 1245
initial management of, 1253–1256
inspection in, 1251
intensity of, 1250
intrinsic disorders and, 1247
management algorithm for, 1247, 1248f
management of, 1247, 1248f, 1253–1256
medical history in, 1248–1249, 1249t
medications for, 1254
mode of onset, 1250
movement testing in, 1251–1252
muscle relaxants for, 1352, 1355–1356
neurologic findings with, 1251, 1252
pain management in, 1253–1256
palpation in, 1251
patient demeanor in, 1252
patient education in, 1253–1254, 1254t
periodicity of, 1250
physical examination in, 1251–1252
physical therapy for, 1254
precipitating factors in, 1250
psychological and social history in, 1251
quality of, 1250
red flags in, 1247–1249, 1249f, 1251, 1253, 1256
reinforcement in, 1247, 1256
relieving factors in, 1250–1251
review (follow-up) in, 1256
site of, 1249–1250
superficial heat for, 1254
supplemental measures in, 1247
time of onset, 1250
triage in, 1247–1253, 1248f
unusual inquiries in, 1248
vigilance in, 1247, 1248f, 1256

5673
 work and, 1255
yellow flags in, 1256
alternative medicine for, 145–146
biomechanical considerations in, 1486–1487
body awareness therapy for, 1551
breath pattern retraining for, 1551
chronic, 1259–1282
accepted causes of, 1261
aggravating factors in, 1263
ancillary investigations in, 1265–1269
assessment of, 1261–1265
associated features of, 1263
biopsychosocial model of, 1261
causes of, 1260
circumstances of onset, 1263–1264
clearance in, 1265, 1278
definition of, 1259
disk stimulation in, 1267–1268, 1267f
distribution of, 1262
drug therapy for, 1271, 1278
duration of, 1262
functional restoration in, 1274
intensity of, 1262–1263
invasive treatments for, 1277–1278
lumbar medial branch blocks in, 1268, 1269f, 1278
magnetic resonance imaging in, 1265, 1266–1267, 1266f, 1267f,
1278
medical history in, 1261–1264
mode of onset, 1263
multidisciplinary pain management for, 1273, 1278
muscle relaxants for, 1356
periodicity of, 1263
physical examination in, 1264
physical modalities for, 1271–1272, 1278
practitioner imperatives in, 1259

5674
 precipitating factors in, 1263
prevalence of, 1260–1261
provisional diagnosis in, 1265
psychological interventions for, 1272–1273
psychosocial history in, 1264
quality of, 1262
red flags in, 1259, 1262, 1265
referred, 1259–1260
refuted causes of, 1261
relieving factors in, 1263
review of previous investigations, 1264–1265
sacral lateral branch blocks in, 1268–1269
sacroiliac joint blocks in, 1268, 1270f
simple needle treatments for, 1272
sinuvertebral nerve block in, 1268
site of pain, 1262
sources of, 1260
specific, targeted treatments in, 1274
studies not indicated in, 1265–1266
time of onset, 1263
treatment of, 1269–1278
untested causes of, 1261
core stability and, 1486–1487
culture and, 142
definition of, 1245–1246, 1245f
depression and, 80–81
epidemiology of, 1537
exercise therapy for, 1254–1255, 1456, 1537–1545
directional preference, 1540, 1542
elements of, 1538, 1538t
evaluation for, 1537, 1538f
evidence supporting, 1541–1543, 1543t
global, 1540–1543, 1543t
goal of, 1537
individualized program for, 1537, 1538–1541, 1543t

5675
 matching program to patient, 1542
musculoskeletal examination for, 1538
quota programs for, 1539
recommendations based on clinical course, 1539
relapse management in, 1540
spinal stabilization, 1540, 1541–1542
failed back surgery and, 1292–1294 (See also Failed back surgery)
gender differences in, 91
genetics and, 96
group therapy for
behavioral v. exercise and physical therapy, 1456
cognitive-behavioral, 1442, 1443t, 1445t, 1446t, 1449t–1452t, 1454t,
1461
individual treatment v., 1439–1442, 1440t–1441t
mindfulness-based, 1457t, 1459t, 1460t
herbal preparations for, 1551
intradiscal therapies for, 1274, 1278, 1643–1652
ablation, 1646–1647
antibiotic, 1649
biacuplasty, 1647–1648, 1648f
biologics, 1649–1650
chemical, 1648–1649
etanercept, 1649
methylene blue, 1649
percutaneous RF thermocoagulation, 1647–1648
proliferants, 1649
stem cell, 1274, 1650
laser therapy for, 1524–1525
manipulation for, 1254, 1550
massage for, 1254, 1551
Modic lesions and, 1645, 1646f, 1647t, 1648–1649
ovarian cancer and, 639
pathology of, 1643–1645, 1645f, 1646f
patient improvement in ineffective treatment, 124, 124f, 124t
peripheral nerve stimulation for, 1564

5676
 persistent, 1539
plasticity in, 72, 72f
prolotherapy for, 1551–1552
psychological interventions for, 1541
radicular, 1246, 1246f
recurrent, 1539
referred, 1245, 1246, 1246f, 1250, 1259–1260
spinal stenosis and, 1291–1292
subacute, 1539
surgery for, 1283–1287
advent of evidence-based medicine, 1284–1285, 1285f
classification of procedures, 1283, 1283f
effectiveness of, 1283–1286, 1284t, 1285f
before evidence-based medicine, 1283–1284
post evidence-based medicine, 1285–1286
rationale for, 1283
Low cerebrospinal fluid volume headache, 1030, 1030f
Low threshold neurons, 42
Low threshold nociceptors, 24
Low-energy lasers (LLLT), for oral mucositis prevention and treatment,
737, 741, 796
Lower esophageal sphincter
hypertensive, 1038, 1038f
hypotensive, 1038
Lower extremities
neural tension test in, 1481–1482, 1481f
sympathetic and nociceptive nerve supply to, 117t
Lower extremity nerve blocks, 868–884
adductor canal, 872–875, 873f, 874f
ankle, 882–883, 883f
fascia iliaca, 875–876, 875f
lateral femoral cutaneous, 876, 876f, 877f, 1211
local anesthetic dosing in, 888t
lumbar plexus, 868–871, 869f, 870f
obturator nerve, 876–877, 877f

5677
 sacral plexus-sciatic nerve, 877–882, 878f, 879f, 880f, 881f
Lower extremity nerve entrapment, 1677–1678
Lower extremity pain, 1205–1227
foot, 1219–1226
lumbosacral plexopathy and, 1205–1208
nerve entrapment syndromes and, 1208–1219
Lower motor neuron dysfunction, 234t
Lower trunk, of brachial plexus, 1147
Low-FODMAP diet, 1068
Low-intensity pulsed ultrasound (LIPUS), 1526
Low-level laser therapy (LLLT), 1524–1525, 1553
LRN. See Lateral reticular nucleus
Lubiprostone, for opioid-induced bowel dysfunction, 1333–1336, 1341
Lumbar disk stimulation, 1267–1268, 1267f
Lumbar epidural steroid injections. See Epidural steroid injections
Lumbar intervertebral disks, 1260
Lumbar medial branch blocks (LMBBs), 1268, 1269f, 1278, 1603–1605,
1603f, 1604f, 1605t
Lumbar medial branch neurotomy, 1275–1276, 1275f, 1278–1279, 1657–
1660
background of, 1657–1658
effectiveness of, 1659–1660
technique of, 1658–1659, 1659f
Lumbar pain. See Low back pain
Lumbar plexus, anatomy of, 868–869, 869f
Lumbar plexus block, 868–871
clinical effects of, 871
complications of, 870–871
indications for, 868–869
landmarks for, 868–870, 869f
ultrasound guidance for, 870, 870f
Lumbar plexus stimulation, 1564
Lumbar puncture
in childhood cancer, 794–795
in CSF-associated headache, 1030

5678
 in subarachnoid hemorrhage, 254
Lumbar spinal nerve block, 1600
Lumbar spinal pain, 1245–1246, 1245f. See also Low back pain
Lumbar spinal pain of unknown or uncertain origin, 1265
Lumbar spine, cervical spine v., 1140t, 1141f
Lumbar spine fusion, 1283–1287
effectiveness of, 1283–1286, 1284t, 1285f
rationale for, 1283
Lumbar supports, 1272
Lumbar sympathetic block, 1600, 1601f
for childbirth pain, 940, 941, 951
Lumbar zygapophysial joint pain, 1260, 1274–1276, 1603–1605, 1603f,
1604f, 1605t
Lumbosacral compression, neurogenic claudication with, 568
Lumbosacral neurolysis, 716–717
Lumbosacral plexopathy, 1205–1208
abscesses causing, 1208
aneurysms causing, 1208
cancer-related, 655–656, 655t, 659
diabetic and nondiabetic, 1207–1208
diagnosis of, 1205
etiology of, 1205
neoplasms causing, 1205–1207
obstetric-related, 1208, 1209f
radiation-induced, 659, 1207
retroperitoneal hematoma and, 1208
trauma causing, 1208
treatment of, 1205
Lumbosacral plexus
anatomy of, 1205, 1206f, 1207f
imaging of, 262, 1205
Lumbosacral radiculoplexus, 1207–1208
Lung(s)
chest pain from diseases of, 1194t
sympathetic and nociceptive nerve supply to, 115t

5679
Lung abscess, 1194t
Lung cancer, 641–642
brachial plexopathy in, 654
chemotherapy for, 781
comorbidities in, 601
depression in, 630
epidemiology of, 621, 622f
fatigue in, 631–632
pain in, 642
adrenal syndrome of, 756
bone metastases and, 634, 744, 744t
chest wall, 642, 1182–1184
low back, 1251
tumor type and stage of disease in, 638
visceral, 754
palliative radiation therapy for, 766
spinal cord compression in, 661, 776
superior vena cava syndrome in, 1183–1184
Lupus. See Systemic lupus erythematosus
Luschka, joints of, 489, 1138, 1140t, 1141f, 1144f
Lyme disease, neuropathy in, 331
Lymphatic diseases, pain associated with, 570–571
Lymphatic drainage, manual, 1530
Lymphedema praecox, 570–571
Lymphoma, 643
chemotherapy for, 780
epidemiology of, 622f
lumbosacral plexopathy with, 1206–1207
superior vena cava syndrome in, 1184

M
MacDonald, Neil, 763
MacIntyre, Alasdair, 143
MacLagan, Thomas J., 8
Macrosystems, 1495

5680
Magendie, François, 3–4, 4f
Magnesium
for headache prevention, 922–923, 1133
for migraine, 990t
Magnesium sulfate, for neuropathic pain, 1367, 1368t
Magnet therapy, 802
Magnetic hands, 1432
Magnetic resonance angiography (MRA)
in acute headache, 1029
black-blood, 256, 257f
in chronic headache, 256, 256f, 257f
of subarachnoid hemorrhage, 251, 254f, 255–256
of thoracic outlet syndrome, 267, 1176
in trigeminal neuralgia, 1112
of vasculitis, 256, 256f
of venous sinus thrombosis, 254f
Magnetic resonance imaging (MRI)
in adenomyosis, 1087
in bone cancer, 745
in central pain states, 396, 398
in central system sensitization, 318
in cervical spondylotic myelopathy, 1170
in chronic pain evaluation, 317
in cingulotomy, 1701–1702
in deep brain stimulation, 1588–1589, 1588f, 1589f
of epidural abscess, 1761, 1762f
in failed back surgery, 1290–1292, 1294
in headache, 1021, 1029
in interdigital neuroma, 1224, 1225f
in intracranial hypotension, 257–258, 258f
of intrathecal inflammatory mass, 1638, 1639f
in ligamentous injuries, 315
in Lisfranc joint instability, 1221
in low back pain, 1252–1253, 1252t, 1265, 1266–1267, 1266f, 1267f,
1278

5681
 in low volume CSF headache, 1030, 1030f
in lumbosacral plexopathy, 1205
in metastatic spinal cord compression, 772, 773f, 776
in metatarsalgia, 1222
in myofascial pain (trigger points), 515
in neck and arm pain, 1168
in nerve entrapment, 267, 268f, 1673, 1675f
in neurologic injuries, 315
in paroxysmal hemicrania, 1027
in pes cavus, 1219
in pes planus, 1219
in plantar fasciitis, 1220
in posterior tibial tendon insufficiency, 1221
in posttraumatic syringomyelia, 586–587
in raised CSF pressure headache, 1030
in sesamoiditis, 1223
of spinal epidural hematoma, 1760, 1760f
of spine (spinal pain), 258–261, 260f
benign v. malignant findings in, 259–261
claw sign in, 261, 261f, 262f
compression fracture, 259–261
infection/inflammation in, 261, 261f, 262f
in spine surgery evaluation, 1289
of subarachnoid hemorrhage, 254–255
in tarsal tunnel syndrome, 1221
in temporomandibular joint disorders, 1132
in thalamotomy, 1703
in thoracic outlet syndrome, 267, 578, 1176
of thoracic spine, in chest wall pain, 1185, 1185f
in trigeminal neuralgia, 258, 259f, 1112
of uterine retroversion, 1082, 1082f
of vertebral fracture, 1187, 1187f
Magnetic resonance neurography (MRN), 251, 262–267
indications for, 262
magnetic field strength in, 264

5682
 muscle denervation in, 262, 265f–266f, 266–267
neuropathic findings in, 262–264, 265f–266f
optimal, 266
pathologic findings in, 262, 265f
peripheral nerve abnormalities in, 266, 266f
of peripheral nerve entrapment, 267–268
in peripheral nerve stimulation workup, 1563
primary purpose of, 262
small field of view in, 264
of thoracic outlet syndrome, 267
Magnetic resonance spectroscopy (MRS), in fibromyalgia, 530
Magnetic therapy, 1553
Magnetoencephalography (MEG), 62–63
in anterior cingulate cortex, 67
in attention studies, 71
in complex regional pain syndrome, 343, 345
in primary somatosensory cortex, 66
in secondary somatosensory cortex, 67
Magnocellular secretory cells, 64
MAI. See Multidimensional Anger Inventory
Maintenance, in cognitive-behavioral therapy, 1406, 1409–1410
Maitland, G. D., 1497, 1497t
Major depression, 433, 433t
in cancer patients, 629–631
Malabsorption, neuromuscular manifestations of, 332
Maldynia, 16
Malignant psoas syndrome, 1205
Malingering, 13, 299
Mallory-Weiss syndrome, 1195t
Malpractice, 193, 195–198, 676
ASA Closed Claims Project, 1758, 1758t, 1759f
Mana, 1552
Management of Pain (Bonica), 9
Manipulation, 1550
for elderly patients, 934, 935

5683
 for failed back surgery, 1294
for low back pain, 1254, 1550
trigger point, 1552–1555
Manual lymphatic drainage, 1530
Manual muscle testing (MMT), 1483–1484
Manual therapy, 1497, 1497t
for low back pain, 1271
Manubriosternal arthritis, 1189–1190
Manubrium, 1181, 1181f
MAPP. See Multidisciplinary Approach to the Study of Chronic Pelvic
Pain
Maprotiline, for neuropathic pain, 1359–1361, 1360t, 1361t
Marfan syndrome, 569, 921
Marginal zone, 41, 107
Marijuana, 202–203
for cancer pain, 687
for cancer pain in children, 801–802
for neuropathic pain, 1369–1370, 1371t
recreational, 202–203
as Schedule I drug, 203, 687
urine testing for, 1016, 1509, 1509t
Marlowe-Crowne Social Desirability Scale, 1425
Maryland, addiction-related terminology in, 183t
Mas1-related G protein-coupled receptor D (MrgprD), 25, 26
Masked depression, 81, 437
Massage therapy, 145, 1551
for abdominal pain, 1072
for cancer patients, 701, 801
for elderly patients, 934, 935
for low back pain, 1254, 1271, 1551
for myofascial pain, 517
for sickle cell disease pain, 973
for spinal cord injury pain, 593
MAST. See Michigan Alcoholism Screening Test
Mastalgia (breast pain), 1190, 1200t

5684
Mastectomy, pain after, 657, 1190–1191, 1200t
Mastodynia, 1199t
Matching controls, 125–126, 125t, 128t
Maternal hyperthermia, neuraxial analgesia and, 949
Maximum medical improvement, 13
MBCT. See Mindfulness-based cognitive therapy
MBIs. See Mindfulness-based interventions
MBSR. See Mindfulness-based stress reduction
McBurney’s point, 1062
MCC. See Midcingulate cortex
McGill Pain Questionnaire (MPQ), 276–280, 285
for cancer pain, 736
for childbirth pain, 940, 941f
in chronic pain, 320
for GERD-related chest pain, 1051
McGill Pain Questionnaire Short Form, 228–229, 276–280, 277f, 285,
290, 321, 992
McGill Quality of Life Questionnaire, 1734
MCIC. See Minimal clinically important change
MCID. See Minimum clinically important difference
McIver, Ronald, 201
McKenzie, Robin, 1487, 1497, 1497t
McKenzie method, in low back pain, 1252, 1271, 1272, 1487, 1540, 1542
MCPPs. See Multiple-copy prescription programs
MCS. See Motor cortex stimulation
M.D. Anderson Symptom Inventory, 1734
MDQ. See Mood Disorder Questionnaire
Meade, Margaret, 1421
Meaning, pain and narrative in, 143
Meanings of Pain (van Rysewyk, ed.), 142
Measurement of anger, 1398–1399, 1398t
Measurement of pain, 272–294
affect of pain, 276–278, 290
behavior observation in, 289
in busy clinical setting, 289

5685
 in cancer, 736
in childbirth, 940, 941f
in children, 288–289, 809–810, 914–915
diary data for, 274–276, 286
domains in, 274
in elderly, 288–289, 930–931
electronic, 1305
at end of life, 1733–1735
face scale for, 288, 288f
in HIV/AIDS, 992
ideal assessment in, 289
in infants and children, 809–810
intensity of pain, 274–276, 282f, 321, 1303t, 1304, 1771–1772
in low back pain, 1250
in multidisciplinary assessment, 320–321
multiple ratings using diaries, 274–276
need for v. burden of, 289
number or pain problems in, 273–274
in primary care visit, 1727
quality of pain, 278–285, 290, 321
recall ratings v. summary scores in, 274–276
reliability in, 273
selecting best for measure for patient or population, 288–289
simplified measures in, 288–289
spatial characteristics, 285–286, 289–290
in special populations, 288–289, 290
in spine surgery candidates, 1303–1305
temporal characteristics, 286, 290
treatment outcomes of, 290
utility of, 273
validity in, 272–273
Mechanical arm pain, 1138, 1160
Mechanical diagnosis and therapy, 1487
Mechanical joint pain, 485–486
Mechanical neck pain, 1138, 1160

5686
Mechanical sensitivity, of nociceptors, 24
Mechanical ventilation, for acute chest syndrome, 965
Mechanical visceral pain, 751–752
Mechanically insensitive nociceptors, 24
Mechanism-based classification, 17, 17t
Mechanistic views of pain, 2–6
Mechanotransduction, 29–30
Meckel’s cave tumor, 1117
Meclofenamate, 1316t
MEDD. See Morphine equivalent daily dose
Medial branch blocks
cervical, 1234, 1235f, 1602–1603, 1602f, 1603t
lumbar, 1268, 1269f, 1278, 1603–1605, 1603f, 1604f, 1605t
Medial branch neurotomy, 1657–1663
cervical, 1171, 1238–1239, 1239f, 1660–1662
background of, 1660–1661
efficacy of, 1662
technique of, 1661, 1661f
lumbar, 1657–1660
background of, 1657–1658
effectiveness of, 1659–1660
technique of, 1658–1659, 1659f
Medial cord, of brachial plexus, 1147
Medial longitudinal fasciculus, 40f
Medial magnocellular zone, 63
Medial pain system, 436, 1300
Medial prefrontal cortex, motivation and, 1470
Medial reticulospinal tract, 40f
Medial syndrome, 1170t
Median nerve
anatomy of, 1147, 1148f, 1149f, 1151f, 1154t
entrapment of, 249, 1673–1676 (See also Carpal tunnel syndrome)
evaluation of, 1482, 1482f
nerve conduction studies of, 244, 244f, 249
Median nerve block, 863–866, 864f, 865f

5687
Median zone, of brainstem, 63
Mediastinal diseases, chest pain in, 1196t
Mediastinitis, 1196t
Medical director, 1711
Medical factors
ancillary studies of, 317–318
assessment of, 314–318, 314f
evaluation procedures for, 317–318
location of pain, 316–317, 316f
pain history in, 317
physical examination for, 317
red flags in, 314–317
risk factors for delayed recovery, 317
Medical history, 229–231, 239
in cancer pain assessment, 665, 666t
“Medical limbo,” 76
Medical marijuana. See also Marijuana
U.S. Supreme Court decision on, 201, 202–203
Medical model, of cancer pain, 615, 616f
Medical Outcomes Study Short Form-36, 129, 1051, 1304–1305, 1313
Medical Outcomes Study Sleep Scale, 323
Medical practice, in pain management, 177–178
Medicalization of pain, 138–139
Medically unexplained symptoms, 525
Medicare Hospice Benefit, 1732
Medicare Part A, 1732
Medication history, 232, 238–239
Medication overuse, in migraine, 1024–1025
Medication overuse headache (MOH), 989, 1025, 1134
Medieval view of pain, 1
Meditation
for cancer pain, 701
for chronic pain, 1407–1408
group, for chronic pain, 1456
for prostate pain syndrome, 1104

5688
 for rehabilitation, 1500
Medulla oblongata, 62f
in descending modulation of pain, 54–56, 55t, 56f
in pain–ANS interaction, 114
Mefenamic acid, 1316t
MEG. See Magnetoencephalography
Meissner’s (submucous) plexus, 118, 120f
Melanoma
epidemiology of, 622f
spinal cord compression in, 772
Melatonin
for chemotherapy-induced neurotoxicity, 733
for headache prevention, 923
MELD. See Model for End-Stage Liver Disease
Meloxicam, 1316t, 1322
for HIV pain, 994t
intravenous, 1322
Melzack, R., 6, 7f
gate control model of, 6, 18, 52, 60, 83, 1492 (See also Gate control
model)
neuromatrix approach of, 144, 1492, 1492t
Memantine
for neuropathic pain, 1367, 1368t
for phantom pain, 366
for postherpetic neuralgia, 388
Memorial Symptom Assessment Scale, 667, 1734
Memory, fibromyalgia and, 533–534
Men. See also Gender differences, in pain
pelvic pain in, 1096–1107
Meninges
of brain, sympathetic and nociceptive nerve supply to, 115t
of spinal cord, 39, 1142, 1145
Meningioma, painful trigeminal neuropathy with, 1117
Meningitis
diagnostic imaging in, 251

5689
 intrathecal drug delivery and, 715, 1635
NSAIDs and, 1328
pain interventions and, 1760–1761
varicella-zoster, 376
Menstrual cycle, and pain, 94
Menstrual pain. See Dysmenorrhea
Mental control, ironic processes theory of, 1396–1397, 1396t
Mental health screening, 467–468
Mental status, 233
Mentgen, Janet, 1555
Meperidine (pethidine), 1334t, 1345
for acute pain, intravenous patient-controlled, 832t
avoidance in cancer pain, 696
for children, 814t, 815
consumption trends for, 208–209, 208–215, 209f, 211f–214f
hepatic dysfunction and, 689t
in intensive care unit, 1787
intrathecal, 714–715
metabolites of, 1347t
morphine equivalence of, 208
renal dysfunction and, 688t
for sickle cell disease pain, 973
Mephenesin, 1354
Mepivacaine, 1386t
dosing in nerve blocks, 888t
for trigger point injections, 516
Mepolizumab, 547
MEPP. See Miniature endplate potential
Meprobamate, 685
Meralgia paresthetica, 1208, 1670, 1677. See also Lateral femoral
cutaneous nerve entrapment
Merskey, Harold, 2, 7, 11
Mesalamine, for chronic proctitis, 687
Mesencephalic tractotomy, 1704–1705
Mesencephalon

5690
 in descending modulation of pain, 54–56
in nociceptive modulation, 55t
Mesenteric vein thrombosis, acute, 756
Mesmer, Franz Anton, 2, 1421
Mesmerism, 2, 1421
Mesolimbic dopamine system, 64, 1002–1003, 1003f, 1336–1337
Mesosystems, 1495
MET. See Motivation enhancement therapy
Meta-analyses, 133
Metabolism, end-of-life organ dysfunction and, 1736
Metabolites, opioid, 1347t–1348t
Metabotropic GABA receptors, 48
Metabotropic glutamate receptors, 47
Metaphor techniques, 1435
Metastatic spinal cord compression (MSCC), 645t, 661–663, 772–776
bone scan in, 772, 774f
clinical management of, 776
as emergency, 773
imaging of, 772, 773f, 774f, 776
investigations in, 663
mechanism of, 662
neurosurgical intervention for, 773–774
pattern of pain in, 662
presentation and physical findings in, 662–663, 662t
prognosis of, 663
radiation therapy for, 773–776, 775f
radiation tolerance in, 774–776
Metatarsalgia, 1222
Metaxalone, 685, 1352t, 1354
Methadone, 1334t, 1344
for acute pain
continuous epidural, 833t
intravenous patient-controlled, 832t
single-dose neuraxial, 833t
for addiction treatment, 454, 1001, 1008–1009

5691
 androgen deficiency with, 1338
for burn pain, 903
for cancer pain, 689, 692, 698–699, 821–822
for cancer pain in children, 798
cardiovascular effects of, 1341, 1344
for children, 813–814, 814t, 821–822
dose conversions of, 829t
for fibromyalgia, 538
hepatic dysfunction and, 688–689, 689t
for HIV pain, 995
in intensive care unit, 1787
interaction with antiretroviral therapy, 995, 995t
intrathecal, 714–715
metabolites of, 1347t
for neuropathic pain, 1366–1367, 1366t
parenteral, 698–699
for postherpetic neuralgia, 385t
rectal, 1342t
renal dysfunction and, 688t
safety of, 1344
for sickle cell disease pain, 973
subcutaneous, 1736
urine testing for, 1016, 1509, 1509t
Methadone maintenance (MMT) programs, 178, 1001, 1008–1009, 1511–
1512, 1513, 1515
and hyperalgesia, 458–459
Methemoglobinemia, 1389
Methicillin-resistant Staphylococcus aureus (MRSA), 553
Methocarbamol, 685, 1254, 1352t, 1354
Methohexital, in emergency department, 1778
Methotrexate
for ANCA vasculitis, 547
for Dercum disease (adiposis dolorosa), 554
for IBD-associated arthritis, 497
for leukocytoclastic vasculitis, 546

5692
 for polyarteritis nodosa, 547
for psoriatic arthritis, 496
for reactive arthritis, 495
for relapsing polychondritis, 558
for rheumatoid arthritis, 492–493, 492t
Methylene blue, 1649
Methylnaltrexone, 683, 817, 1333, 1341
Methylphenidate, DEA quota for, 177
Methylprednisolone
for cancer pain, 685
epidural injections of, 1611
intralesional injections, for bone pain, 747–748
intrathecal, for postherpetic neuralgia, 1118
for sensory mononeuropathies, 559
Metoclopramide
for migraine, 991t, 1024t
for nausea/vomiting in cancer therapy, 683–684, 684t
for opioid withdrawal, 1764
for opioid-induced bowel dysfunction, 682
Metoprolol, for migraine, 990t
Mexiletine
for central pain, 401t
for neuropathic pain, 1367, 1368t, 1388
for postherpetic neuralgia, 388
for spinal cord injury pain, 591
Mianserin, for tension-type headache, 1133
Michigan Alcoholism Screening Test (MAST), 1509
Michigan Body Map, 532, 533f
Microbial colonization, in abdominal pain, 1067–1068, 1071
Microbiome alteration, 1071
Microcurrent stimulation, 1553
Microneurography, 25b
Microscopic polyangiitis (MPA), 545t, 547
Microsporidium, in HIV/AIDS, 986
Microsystems, 1495

5693
Microvascular decompression (MVD)
for glossopharyngeal neuralgia, 1122
for nervus intermedius neuralgia, 1119–1120
for trigeminal neuralgia, 1110, 1115–1116, 1691–1694, 1693f, 1694f
for vagal neuralgia, 1122
MIDAS. See Migraine Disability Assessment Scale
Midazolam
for baclofen withdrawal, 1764
for central pain, 403
for dying patients, 1737, 1739–1740, 1739t
in emergency department, 1778
intrathecal, 715
Midbrain, 62f
Midbrain reticular formation, in descending modulation of pain, 55
Midcingulate cortex (MCC), 66f, 67
Middle cervical ganglion, 112, 113f
Middle glenohumeral ligament, 1157
Middle trunk, of brachial plexus, 1147
Middle-fossa syndrome, 653
Midline retroperitoneal syndrome, 754
Migraine, 1021–1025, 1133
acute attack therapies for, 1023–1024, 1024t
new advances in, 1024
nonspecific, 1024, 1024t
specific, 1024, 1024t
strategies for, 1024
amygdala in, 70
in children, 910, 922–923
clinical features of, 1021
diagnostic criteria for, 1021, 1021t, 1133
diagnostic imaging in, 251, 251t, 1022
frequent or chronic, 1021–1022
functional imaging of, 1020, 1020f
gender differences in, 91
genetics of, 1019–1020

5694
 health care costs of, 1021
in HIV/AIDS, 989, 990t–991t
hypnosis for, 1430–1431
management principles for, 1022
medication overuse in, 1024–1025
neurostimulation for, 1023, 1023t, 1024
nonpharmacologic management of, 1022, 1133
ophthalmoplegic, 1113
pathophysiology of, 1019–1020, 1020f
peripheral nerve stimulation for, 1565–1566
pharmacologic management of, 990t–991t, 1022–1025, 1133
preventive treatments for, 1022–1023, 1023t, 1133
stepped care for, 1024
stratified care for, 1024, 1024t
Migraine Disability Assessment Scale (MIDAS), 1022, 1022f
Migraine hangover, 1133
Military position, 577
exaggerated, 1166
Milk of magnesia
for opioid-induced constipation, 799
for oral mucositis, 737
Milnacipran
for depression, 438–439
for fibromyalgia, 536t, 537
for postherpetic neuralgia, 386
Milton H. Erickson Foundation, 1434
Mind–body issues, 410–411
Mind–body therapies, 145–146
Mindfulness, 1405
Mindfulness meditation, 1407–1408, 1500
Mindfulness-based cognitive therapy (MBCT), 1410, 1439, 1456
Mindfulness-based interventions (MBIs), group, for chronic pain, 1439,
1456, 1457t–1460t
Mindfulness-based stress reduction (MBSR)
for failed back surgery, 1295

5695
 group, for chronic pain, 1439, 1456
Mineral oil, 799
Mineralizing oral solution, for mucositis, 740
Miniature endplate potential (MEPP), 507
Minimal clinically important change (MCIC), in low back pain, 1286
Minimal sedation, 900t, 1777
Minimization, in studies, 127
Minimum clinically important difference (MCID), 13–14
Minnesota Multiphasic Personality Inventory (MMPI), 16, 444–445, 1304,
1393
Minnesota Multiphasic Personality Inventory-2-Restructured Form, 1398t,
1399
MIRE. See Monochromatic infrared energy
Mirogabalin, for neuropathic pain, 1374
Mirror therapy, 795, 1497, 1531–1532
Mirtazapine, 365, 1133
Miscarriage
pelvic pain in, 1081–1082
surgical management of, 1081
types of, 1082t
Mismatch (wrong surgery), and failed back surgery, 1288
Misoprostol
for erythromelalgia, 559
for gastric protection with NSAIDs, 1327
Misuse. See also Opioid abuse or misuse; Substance abuse
definition of, 1002t
Mitchell, Silas Weir, 8–9, 9f, 363, 1668
Mitral valve prolapse, 1193t
Mittelschmerz, 1084
Mixed agonist-antagonist opioids, 1334t, 1338
MMPI. See Minnesota Multiphasic Personality Inventory
MMT. See Manual muscle testing; Methadone maintenance (MMT)
programs
Model for End-Stage Liver Disease (MELD), 688
Model Guidelines for the Use of Controlled Substances for the Treatment

5696
 of Pain, 181
Model List of Essential Medicines (WHO), 206, 208
Model Policy on the Use of Opioid Analgesics for the Treatment of
Chronic Pain, 181, 184
Moderate sedation, 900, 912t, 1777
Modic lesions, 1645, 1646f, 1647t, 1648–1649
Modified STarT Back tool, 230
Modifiers of pain, 321
Modulatory mechanisms, 52–61
biologic significance of, 64
CNS sites involved in, 54–55, 55t
neurotransmitters in, 55, 55t, 57, 60
ON, OFF, and NEUTRAL neurons in, 57–58
spinal cord-based, 52–53
acute segmental, 52, 52f
central sensitization, 53
C-fiber wind-up, 53, 53f
heterosegmental, 53
propriospinal, 53
supraspinal, 53–58, 56f
cortical structures in, 55, 55t, 57
in neonates, 809
periaqueductal gray in, 54–56, 55t, 56f, 63–64
substrates mediating descending modulation, 54–57, 56f, 108–109
tonic descending, 53–54, 54f
triggers of clinical hypersensitivity in, 58–60
MOH. See Medication overuse headache
Moldofsky, H., concept of fibromyalgia, 525–526
Molecular gaze, 143–144
“Molecular vision of life,” 137
Mondor disease, 1190, 1200t
Monitoring, of prescriptions, 181–182, 184, 187, 231–232, 297–298
Monoamine oxidase inhibitors (MAOIs), 438, 442, 444
Monoamines, 49. See also Norepinephrine; Serotonin
Monoarthritis, 485, 486t

5697
Monochromatic infrared energy (MIRE), 1525
Monoclonal gammopathy, 333
Mononeuritis multiplex, 657, 989
Mononeuropathy(ies)
sensory, 559
tumor-related, 653
Mononeuropathy multiplex syndromes, painful, 334–335
Monopolar electromyography, 247
Monson, Diane, 202
Montana, physician-assisted death in, 202
Mood, 79–80. See also Depression
assessment of, 227, 229–230
and doctor–patient relationship, 476–477
opioid analgesics and, 1337
and spine surgery, 1303t, 1304
Mood Disorder Questionnaire (MDQ), 229
Mood states. See also Depression
assessment of, 322
Moore, Daniel, 1751
Moore, James, 8
MOR. See μ-Opioid receptor
Moral order, in dying, 159
Morals, and ethics, 1745
Morehouse, George R., 9
Morphine, 1334t, 1344
abuse-deterrent formulations of, 1349t
for acute pain
continuous epidural, 833t, 834
in elderly, 839
intra-articular, 837
intravenous patient-controlled, 832, 832t
single-dose neuraxial, 833, 833t
subarachnoid, 851–852
in war trauma, 838
allergy to, 1344

5698
for burn pain, 903
for cancer pain, 689, 690t, 691, 698–699, 746–747, 821–822
for cancer pain in children, 798
cardiovascular effects of, 1341
for central pain, 402–403
for childbirth pain, 947t, 948
for children, 813, 814t, 821–822
consumption trends for, 208–215, 209f, 211f–214f
desirable and undesirable properties of, 1336, 1336t
dose conversions of, 829t
for elderly patients, 933
in emergency department, 1775, 1776, 1776t
as essential medicine, 206
extended-release, 690t
hepatic dysfunction and, 689t
for HIV pain, 994t, 996
hypothalamic effects of, 1338
in intensive care unit, 1786
interaction with antiretroviral therapy, 995t
intracerebroventricular, 699
intrathecal, 714–715, 714t, 1623, 1624–1625, 1624f, 1625t
for acute pain, 851–852
for neuropathic pain, 1375
side effects of, 1637
for spinal cord injury pain, 592
trial of, 1631–1632, 1631t
liposomal, 833
metabolites of, 1347t
myoclonus with, 1737
for neuropathic pain, 402–403, 1366–1367, 1366t, 1375
as opioid agonist, 1336
parenteral, 698–699
for phantom pain, 365–366
for postherpetic neuralgia, 385t, 387, 388
rectal, 1342t, 1343

5699
 renal dysfunction and, 688t
for sickle cell disease pain, 973
for spinal cord injury pain, 592
subcutaneous, 1736
topical, 737, 1736
urine testing for, 1016, 1016f, 1509, 1509t
Morphine equivalence, 208
milligram, 993–995, 1002
parenteral, 829
Morphine equivalent daily dose, 186, 310
Morphine Manifesto, 218
Morris, David, 151
Morton, William T. G., 8
Morton’s neuroma, 1224–1225, 1225f, 1670–1671
Motivation
for behavioral change, 1470–1479, 1728–1730
agreement with twist in, 1475
amplified reflection in, 1475
dealing with setbacks and resistance, 1474–1475, 1475t
decisional balance in, 1471–1473, 1473t
double-sided reflection in, 1475
personal choice and control in, 1475
problem and goal recognition in, 1473–1474
self-motivational statements for, 1474
shifting focus in, 1476
simple reflection in, 1475
transtheoretical model of, 1471–1472
volitional approach in, 1476–1477
neural mechanisms of, 1470–1471
Motivation enhancement therapy (MET), 1472–1476, 1472t
research outcomes in, 1476
traps to avoid in, 1474
Motivational interviewing, for substance use disorder, 462, 1512
Motivational-affective system, 65, 83
Motor cortex, in nociceptive modulation, 57

5700
Motor cortex stimulation (MCS), 1587, 1589–1591
for anesthesia dolorosa, 1123
basic considerations in, 1589–1590
for central pain, 403–404
efficacy of, 1590
indications for, 1589
for spinal cord injury, 593
surgical technique for, 1590–1591, 1590f, 1591f
Motor endplate, 507–508, 507f
Motor exam, in neck pain, 1163, 1163t
Motor function tests, 234, 234t, 1483–1484
Motor nerve conduction studies (MNCS), 244–245, 245f
F-wave, 245, 246f
H-reflex, 245
repetitive, 245, 246f
Motor neuron dysfunction, 234t
Motor neuropathy, in herpes zoster, 376, 376f, 381
Motor skills, opioid effects on, 697–698
Motor system syndrome, 1170t
Motor unit potentials (MUPs), 248, 248f, 248t
Motor-level stimulation, 1526–1527
Motor/movement disorders, in complex regional pain syndrome, 345
Movement, fear of, 78, 80, 226, 227, 230
Movement testing, in low back pain, 1251–1252, 1264
MPI. See Multidimensional Pain Inventory
MPQ. See McGill Pain Questionnaire
MPS. See Myofascial pain syndrome
MRA. See Magnetic resonance angiography
MRN. See Magnetic resonance neurography
MRS. See Magnetic resonance spectroscopy
MRSA (methicillin-resistant Staphylococcus aureus), 553
MS. See Multiple sclerosis
Mucositis. See Oral mucositis
Mulder’s sign, 1224
Müller, Johannes, 4, 4f, 6

5701
Multiaxial classifications, 18
MultiCare Tacoma General Hospital, 1709
Multicenter Study of Hydroxyurea (MSH), 963, 976
Multichannel intraluminal impedance, in noncardiac chest pain, 1045
Multidimensional Anger Inventory (MAI), 1398t, 1399
Multidimensional Fatigue Inventory, 632t
Multidimensional Pain Inventory (MPI), 18, 320, 397, 1304
Multidimensional Pain Inventory (MPI) Interference Scale, 323
Multidimensions, of pain, 225–226, 226f
Multidisciplinary approach, 7–8, 9, 1490, 1717. See also Interdisciplinary
approach
in chronic pain, 1709
cognitive-behavioral therapy in, 429
interdisciplinary management v., 1709, 1710–1711
in occupational therapy, 1501
Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP),
1088
Multidisciplinary assessment, 313–327
conceptual model for, 313–314
conundrums in, 313
of functional impact, 323
of medical factors, 314–318, 314f
ancillary studies of, 317–318
evaluation procedures for, 317–318
location of pain, 316–317, 316f
pain history in, 317
physical examination for, 317
red flags in, 314–317
risk factors for delayed recovery, 317
organization of, 324
of physical capacity, 323–324
of psychological factors, 318–323
brief (ACT-UP), 319, 319t
as cause v. consequence, 318–319
as concomitants v. precursors, 319

5702
 elements of evaluation, 319–321
interviews for, 319–320, 320t
problem areas to assess, 321–323
self-report inventories in, 320–321
of social factors, 324
Multidisciplinary (interdisciplinary) pain center, 14, 324, 1494
Multifocal motor neuropathy (MMN), 329–330
Multimodal analgesia, 850
Multiorgan failure, acute, in sickle cell disease, 969
Multiple myeloma, 643, 1188f
Multiple ratings, of pain, 274–276
Multiple sclerosis (MS)
central pain in, 398–405
mechanisms of, 399–400
neuromodulation for, 403–404
neurosurgical management of, 403–404
pharmacotherapy for, 400–403, 401t
psychological and physiotherapy treatment for, 403
neuraxial analgesia in, 853
painful trigeminal neuropathy in, 1117
trigeminal neuralgia in, 398, 1112
Multiple-copy prescription programs (MCPPs), 174, 182
μ-Opioid receptor (MOR), 48, 1333–1336, 1335f
MUPs. See Motor unit potentials
Muscarinic receptors, 118
Muscle denervation, magnetic resonance neurography of, 262, 265f–266f,
266–267
Muscle nociceptors
activation of, 508–509
in cancer pain, 627–628
Muscle pain, 504. See also Myofascial pain; Myofascial pain syndrome
controversy over, 504
historical overview of, 504
medical evaluation of, 315–316
referral patterns of, 504, 505f

5703
Muscle physiology, 506–508
Muscle relaxants
skeletal muscle, 685, 1352–1356, 1352t
for ankylosing spondylitis, 1188
for failed back surgery, 1295
indications for, 1352, 1353t
for low back pain, 1254, 1271, 1352, 1355–1356
mechanism of action, 1352–1354, 1353f, 1354t
for migraine, 991t
for noncardiac chest pain, 1051–1052
for prostate pain syndrome, 1104
sedative-hypnotic, 1352t, 1354
tricyclic antidepressant-like, 1352t, 1354–1355
smooth muscle, for abdominal pain, 1071
Muscle strength, 1497–1498, 1502–1503
Muscle testing, 233, 1163, 1163t
Muscle tone, 233, 234
Muscular endurance, 1497–1498
Musculocutaneous nerves, 1147, 1148f, 1151f, 1154t
Musculoskeletal injuries, medical evaluation of, 315
Musculoskeletal pain
adjuvant analgesics for, 685
chest wall, 1180, 1180t, 1197t–1198t
in children, 909–910, 920–921
diffuse or widespread, 921
in HIV/AIDS, 987
mindfulness-based group therapy for, 1458t, 1460t
after spinal cord injury, 582–584, 585f, 587f
back, 583–584
elbow and wrist, 583
nonpharmacologic treatment of, 588
pharmacologic treatment of, 588–590
shoulder, 582–583
spasticity-related, 584, 589–590
surgical treatment of, 589

5704
Musculoskeletal rehabilitation
adverse neural tension in, 1481–1482, 1481f–1483f
basic considerations in, 1480–1481
biomechanics of, 1480–1489
definition of, 1480
kinetic chain theory in, 1480–1481
neuromuscular control in, 1482–1483
Music therapy, 701, 800–801
Mutuality, 1745, 1748–1749
MVD. See Microvascular decompression
Myalgia, epidemic, 1190
Mycobacterium avium complex (MAC), 986
Mycobacterium tuberculosis, in HIV/AIDS, 986
Mycophenolate mofetil
for bullous pemphigoid, 558
for epidermolysis bullosa, 558
for leukocytoclastic vasculitis, 546
for pemphigus vulgaris, 557
for polyarteritis nodosa, 547
Mycoplasma genitalium, 1080
Myelin neuropathy, 330
Myelitis, varicella-zoster, 376
Myelopathy
cancer-related, 654
cervical, 1138, 1162–1163
cervical spondylotic, 1169–1170, 1170t
chest pain in, 1196t–1197t
radiation, 658–659
Myelotomy
for cancer pain, 728–729, 760
complications of, 729
dorsal, 760
indications for, 728
open limited, 728–729
outcomes of, 729

5705
 percutaneous RF lesioning, 728, 729f
technique of, 728
Myenteric plexus, 118, 120f
Myocardial infarction, 1193t
NSAIDs and, 1324–1326
Myoclonus
at end of life, 1737
opioid-induced, 1737
Myofascial pain, 1233
arm and neck, 1160
cancer-related, 613, 627–628
chest wall, 1190, 1199t
laser therapy for, 518, 1524–1525
medical evaluation of, 315–316
temporomandibular joint, 1131–1132, 1132t
trigger point manipulation for, 1552
ultrasound therapy for, 518, 1526
Myofascial pain syndrome (MPS), 504–524, 627, 627t
basic concepts of, 504–506
biochemical milieu of, 511–513
catecholamines and ANS in, 511–512
central sensitization and, 509–511
Cinderella hypothesis of, 508
clinical management of, 513–518
cytokines in, 512–513
diagnosis of, 513–514
energy crisis hypothesis of, 504
historical perspective on, 504
integrated trigger point hypothesis of, 504–506, 510–511
interdisciplinary meanings of, 513
introduction of term, 504
magnetic resonance imaging of, 515
motor endplates and, 507–508
muscle nociceptor activation and, 508–509
muscle physiology and, 506–508

5706
 needling therapies for, 515–517
neuropeptides and inflammatory mediators in, 511, 512f
patient education on, 515
peripheral sensitization and, 508–509
pH and, 511
physical examination in, 513–514
referred pain patterns in, 505f, 514
shockwave emitters for, 515
treatment of, 515–518
invasive, 515–517
noninvasive, 517–518
ultrasound of, 515
Myofascial release therapy, 539
Myofibrils, 506
Myopalladin, 506, 507f
Myopathy, in HIV/AIDS, 989
Myosin, 506–507, 507f
Myotomal pain, 602, 613, 1160
Myotomes, 1145, 1150f
The Mystery of Pain (Dickinson poem), 172
Myths, as barrier to pain relief, 1725

N
Nabilone
for cancer pain, 687
for cancer pain in children, 801
for fibromyalgia, 537, 537t
for neuropathic pain, 1371t
Nabiximols, for cancer pain, 687, 801
Nabumetone, 994t, 1316t
Nadolol, for migraine, 990t
Nafe, John Paul, 6
Nalbuphine, 1334t, 1346
for acute pain, intravenous patient-controlled, 832t
avoidance in cancer pain, 696
for burn pain, 902

5707
 in emergency department, 1776
metabolites of, 1348t
for opioid-induced pruritus, 1341
respiratory depression with, 1338
Naloxegol, 683, 1333, 1341
Naloxone
for fentanyl reversal, 815
as opioid antagonist, 1336
for opioid side effects, 817, 1338
Naltrexone
for fibromyalgia, 537t, 538
long-acting injectable, 1514
for substance use disorder, 454, 1513, 1514–1515
Naprosyn, for HIV pain, 994t
Naproxen, 1316t, 1321–1322
for acute pain, 829–830
cardiovascular effects of, 1325
central nervous system effects of, 1328
for children, 812t, 922
for elderly patients, 932
for gout, 500
for low back pain, 1254
for migraine, 991t, 1024, 1024t, 1025, 1133
for neuropathic pain, 1369
Naproxen plus esomeprazole, 1323–1324
Naramore, L. Stanley, 198–199, 201
Naratriptan, 990t–991t, 1024t
Narcotic. See also Opioid(s)
definition of, 174, 206, 1333
Narcotic bowel syndrome, 1069
Narcotics Anonymous, 1511, 1513
Narrative, Pain, and Suffering (Carr, Loeser, Morris, eds.), 143
Narrative medicine, 143–144, 1749
NAS. See Novaco Anger Scale
Nasal fentanyl, 1735

5708
Nasociliary neuralgia, 1122–1123
NASPER. See National All Schedules Prescription Electronic Reporting
Act of 2005
National Academies of Sciences, Engineering, and Medicine, 176
National Academy of Medicine, 1794
National All Schedules Prescription Electronic Reporting Act of 2005
(NASPER), 182
National Ambulatory Medical Care Survey, 95
National Cancer Institute, 173
National Cancer Institute Common Terminology Criteria for Adverse
Events, 635, 635t
National Center for Complementary and Alternative Medicine (NCCAM),
145, 1547
National Center for Complementary and Integrative Health (NCCIH),
1547–1548, 1549
National Health and Nutrition Examination Survey (NHANES), 94
National Health Interview Study (NHIS), 91, 94
National Institutes of Health (NIH)
on acupuncture for pain, 701–702
on chronic overlapping pain conditions, 525
on pain management, 173, 185
pain medicine in, 1793
PROMIS initiative of, 227, 1313
on prostatitis, 1099, 1103–1104
on sickle cell disease, 958–959
National Institutes of Health Pain Consortium, 129
National Institutes of Health Task Force on Research Standards for
Chronic Low Back Pain, 129
National Pain Care Policy Act of 2008 and 2009, 1793
National Pain Strategy (NPS), 185, 1490, 1793–1794
Native Americans, pain and pain response in, 139–140
Natural medicine, 1549, 1551
Naturalistic approaches, 1434–1435
Nausea
abdominal pain and, 1064

5709
 in cancer patients, 617
antiemetics for, 683–684, 684t
chemotherapy-induced, 683, 684, 701
opioid-induced, 683–684, 684f
radiation therapy–induced, 683
neuraxial administration and, 835–836
opioid-induced, 1337
in children, 816–817, 817t
tolerance to, 1338–1339
NCA. See Nurse-controlled analgesia
NCCAM. See National Center for Complementary and Alternative
Medicine
NCCIH. See National Center for Complementary and Integrative Health
NCCP. See Noncardiac chest pain
NCLFUS. See Noncontrast low-frequency ultrasound
NCPB. See Neurolytic blockade, celiac plexus
NCS. See Nerve conduction studies
NDA. See New drug application
NDPH. See New daily persistent headache
Near-infrared spectroscopy (NIRS), 62–63
Nebraska, addiction-related terminology in, 183t
Nebulin, 506–507, 507f
Nebulized opioids, 1343
Neck
anatomy of, 1138–1158
biomechanics of, 1138
musculature of, 1141, 1143f
nerve supply to muscles of, 1152t
Neck Disability Index, 232
Neck dissection, for cancer, 658, 733–734
Neck pain, 1138–1179, 1230–1244
acute, 1231–1233
definition of, 1231
inflammatory causes of, 1233
rare conditions causing, 1233

5710
 serious conditions causing, 1232–1233
spurious conditions causing, 1233
synopsis of causes, 1232t
age and psychosocial history in, 1161
anatomy in, 1138–1158
brachial plexus, 1146–1150, 1147f, 1148f, 1148t
cervical nerves, 1143–1146, 1145f, 1146f
cervical plexus, 1146, 1146f, 1147f
cervical spine, 1138–1141, 1139f, 1144f
dermatomes, 1145, 1147f
musculature, 1141, 1143f
pectoral girdle and shoulder, 1150–1158, 1155f, 1156f, 1157f
vertebral arteries, 1142–1143, 1145f
vertebral canal, 1142, 1144f
associated symptoms in, 1160–1161
axial v. radicular, 1138
biomechanical considerations in, 1484–1485
cervical disk stimulation in, 1234, 1234f
chronic, 1233–1235
definition of, 1233
peripheral nerve stimulation for, 1565
prevalence of, 1234–1235
clinical pathway for managing, 1240, 1241f
coexisting conditions with, 1161t
common causes of, 1138, 1168–1176
conservative therapy for, 1238
definition of, 1230, 1230f
diagnosis in, pursuing, 1231–1238
differential diagnosis of, 1150, 1159
dorsal rhizotomy or ganglionectomy for, 1680
electrodiagnostic studies in, 1168
epidemiology of, 1158–1159
family history in, 1161
general observations in, 1162
history of, 1159–1161, 1231

5711
 idiopathic, 1233
inspection and palpation in, 1163–1164
interventional pain medicine for, 1238–1239
laboratory examination in, 1166–1168
laser therapy for, 1524–1525
location/radiation of, 1160
mechanical, 1138, 1160
medial branch blocks in, 1234, 1235f
medial branch neurotomy in, 1238–1239, 1239f
modifying factors and drug history in, 1160
motor exam in, 1163, 1163t
myofascial, 1160
neurologic exam in, 1162–1163
neuropathic, 1160, 1163
nonmechanical, 1160
onset of, 1159, 1160
past medical history and systems review in, 1161
patient evaluation in, 1159–1168
physical examination in, 1162–1167
quality of, 1160
radiographic studies in, 1168–1169, 1167t, 1168f
red flags in, 1161t
referred, 1160, 1164, 1164f–1165f
reflex testing in, 1163, 1164t
sensory exam in, 1163
skeletal, 1160
special tests in, 1165–1166
surgical history in, 1161
trauma and, 1231
treatment of, 1238–1239
whiplash and, 1235–1236, 1235f, 1236f
widespread, 1233
Necrotizing fasciitis, 552
Necrotizing soft tissue infection, 552
Necrotizing vasculitis, 329

5712
Needle electromyography. See Electromyography
Needle through needle technique, of combined spinal-epidural analgesia,
852
Needle treatments, for low back pain, 1272
Needling therapies, for myofascial pain (trigger points), 515–517
Nefazodone, 439
Negative affectivity, 77
Negative cognitive triad, 437
Negative sexual encounters, and pelvic pain, 1084, 1099, 1100
Neisseria gonorrhoea, 1080
Nemec, Hans, 1527
NEO Personality Inventory, 444
Neoadjuvant chemotherapy, 778
Neoplasms. See also Cancer; Tumor(s)
chest wall pain with, 1182–1184
skin, painful, 560, 560f, 561t
Neospinothalamic tract (nSTT), 43, 108f
Neostigmine, intrathecal, 715, 1628
Nerve blocks, 856–857, 1385, 1595–1610. See also specific blocks
for abdominal pain, 1070–1071
for acute pain, 836–837, 1607
blind techniques for, 1597
for burn pain, 903
for childbirth pain, 940, 950–951
for children, 819–821
for chronic pain, 1607
for chronic pain evaluation, 317–318
common principles of, 1595–1599
for complex regional pain syndrome, 354
complications of, 886–888, 1596–1597
inflammatory, 887
neurologic, 886–887, 887t
nonneurologic, 887
contraindications to, 1596
diagnostic, 1600–1605

5713
 applications of, 1602–1605
controls for, 1601
criteria for positive response in, 1601–1602
principles of, 1601–1602
rationale for, 1600
for herpes zoster, 378–379, 390, 1186
image-guided, 268, 1597–1599, 1598f
for intercostal neuralgia, 1186, 1186f
local anesthetic toxicity in, 887–888
lower extremity, 868–884
adductor canal, 872–875, 873f, 874f
ankle, 882–883, 883f
fascia iliaca, 875–876, 875f
femoral nerve, 871–872, 871f, 872f
lateral femoral cutaneous, 876, 876f, 877f, 1211
local anesthetic dosing in, 888t
lumbar plexus, 868–871, 869f, 870f
obturator, 876–877, 877f
sacral plexus-sciatic nerve, 877–882, 878f, 879f, 880f, 881f
lumbar plexus, 868–871
for male pelvic pain, 1104
mechanism of action, 1595
nerve damage in, 1597
for nervus intermedius neuralgia, 1120
nonneural structure damage in, 1597
for nummular headache, 1123
paravertebral, 866–868, 888t
patient factors in, 1595
for phantom pain, 364, 366
physician factors in, 1595
physiologic effects of, 1596–1597
placebo effects v., 1600, 1601–1602, 1605, 1607–1608
for postherpetic neuralgia, 389, 1118, 1186
for postsurgical breast pain, 1190–1191
preparation for, 1595–1596

5714
 procedure for, 1597–1599
prognostic, 1599–1600, 1599t
quadratus lumborum, 883–885, 884f
for rib fracture pain, 1188, 1189
systemic effects of, 1596
test, 1599
therapeutic, 1607–1608
thoracic wall, 885–886
training and credentialing for, 1756–1757
for trigeminal neuralgia, 1115
upper extremity
axillary, 861–862, 862f, 864f
brachial plexus terminal branch, 863–866
infraclavicular, 820, 859–861, 860f, 861f
interscalene, 857–858, 857f, 858f
local anesthetic dosing in, 888t
supraclavicular, 820, 858–859, 859f
suprascapular, 862–863, 863f, 1607
Nerve conduction studies (NCS), 243–246, 1673
applications of, 249–250
cranial nerve, 246
in femoral nerve entrapment, 1212
in fibular nerve entrapment, 1218
in lateral femoral cutaneous nerve entrapment, 1210
in lumbosacral plexopathy, 1205
motor, 244–245, 245f
F-wave, 245, 246f
H-reflex, 245
repetitive, 245, 246f
in neck and arm pain, 1168
in neuropathy, 250, 330
in obturator nerve entrapment, 1215
parameters recorded during, 244
in pes cavus, 1219
sacral nerve, 246

5715
 in saphenous nerve entrapment, 1214
in sciatic nerve entrapment, 1217
sensory, 244, 244f, 245f
stimulator probe for, 243–244, 244f
in tarsal tunnel syndrome, 1221
in thoracic outlet syndrome, 578
Nerve conduction velocity, 244
Nerve energies, law of specific, 4, 6
Nerve entrapment, 267–268. See also specific nerves and syndromes
clinical findings in, 1672–1673
electrodiagnostic studies in, 249, 1673
electrodiagnostic tests in, 249
in failed back surgery, 1289–1290, 1289t
imaging studies in, 1673, 1674f, 1675f
pathophysiology of pain in, 1672
and systemic disease, 1672
upper extremity, 1138, 1173–1174, 1174t
Nerve entrapment release, 1668, 1672–1678
clinical considerations in, 1672–1673
lower extremity, 1677–1678
median nerve, 1673–1676
radial nerve, 1676–1677
suprascapular nerve, 1677
thoracic outlet, 579, 1677
ulnar nerve, 1676
Nerve growth factor (NGF), 32, 106
in cancer pain, 627, 732, 745
for HIV pain, 996
in pelvic pain, male, 1100
Nerve injury
catastrophic, 1765–1767, 1767f
malpractice claims over, 1758, 1759f
peripheral nerve blocks and, 886–887, 887t
upper extremity, 1163t
Nerve ischemia, 1672

5716
Nerve root avulsion, magnetic resonance neurography of, 265f
Nerve root sensory areas, 234t
Nerve root testing, 234t
Nerve root tethering, 587
Nervi nervorum, 1668–1669
Nervous tension, 1025
Nervus intermedius neuralgia, 1112, 1118–1120, 1119f, 1129
Neural mobilization, 1481
Neural plasticity, 14
Neural tension, adverse, 1481–1482, 1481f–1483f
Neuralgia. See also specific neuralgias
cranial, 1108–1127
definition of, 14
postsympathectomy, 573
Neuralgia of the fifth. See Trigeminal neuralgia (classical)
Neuralgic amyotrophy, 330, 334–335
Neuraxial analgesia, 1343, 1385. See also Epidural analgesia;
Subarachnoid analgesia
for acute pain, 833–836
continuous epidural, 833–836
dosage recommendations for, 833t
outcome studies of, 835–836
patient-controlled, 835, 836t
side effects of, 834–835
single-dose opioid, 833, 833t
for central and peripheral analgesia, 853–854
for childbirth pain, 940, 946–950
advantages and disadvantages of specific techniques, 947t
complications of, 949
contraindications to, 946
side effects of, 949
complications of, 852–853
contraindications to, 853
in intensive care unit, 1787–1788
neural injuries in, 1765–1767, 1767f

5717
 safety guidelines for, 1766–1767
Neurilemmoma (schwannoma), 265f, 560, 561t
Neuritis, 14
Neuroablation, for central pain, 404
Neuro-algodystrophy. See Complex regional pain syndrome
Neuroaugmentive techniques, for postherpetic neuralgia, 389
Neuroaxial blocks
for herpes zoster, 378–379
for postherpetic neuralgia, 390
Neurocirculatory asthenia, 1191, 1201t
Neurodynamics, 1481–1482, 1481f–1483f
Neurofibromas, lower extremity, 1206
Neurogenic claudication, 568, 1290
Neurogenic edema, 233
Neurogenic inflammation, 342
Neurogenic pain, 264
definition of, 14
peripheral, 14
Neurogenic thoracic outlet syndrome, 267, 576–577, 576t, 1176. See also
Thoracic outlet syndrome
Neurokinin A, 420
Neurokinin-1, in cancer pain, 744, 758
Neurolinguistic programming (NLP), 1434
Neurologic exam, 233–235
in low back pain, 1264
in neck pain, 1162–1163
in neuropathy, 330
Neurologic injury, in intrathecal drug delivery, 1635–1636
Neurological injuries, medical evaluation of, 315
Neurolymphoma, 626–627
Neurolysis, definition of, 1653
Neurolytic blockade, 1653–1667
celiac plexus, 711, 711t, 717–719, 718f
chemical, 711t, 716–717, 716f, 1653, 1654
cryoneurotomy, 1653, 1654–1655

5718
 ganglion of impar, 720–721, 720f, 759
history and trends in, 1653
limitations of, 1653–1654
physical modalities for, 1653
principles of, 1653
spinal, 711t, 716–717
adverse effects of, 717
contraindications to, 717
technique of, 716, 716f
superior hypogastric plexus, 711t, 719–720, 719f, 720f
thermal radiofrequency, 1653, 1655–1664
for ankylosing spondylitis, 1188
applications of, 1656–1664
for brainstem procedures, 1657
for central ablative procedures, 1656–1657
cervical medial branch, 1172, 1238–1239, 1239f, 1660–1662, 1661f
for cordotomy, 1657
for discogenic pain, 1295
for dorsal root entry zone lesions, 1657
efficacy of, 1555t
for intercostal neuralgia, 1186
lumbar medial branch, 1275–1276, 1275f, 1278–1279, 1657–1660,
1659f
occipital, 1239–1240, 1240f
pathology of, 1656
physics of, 1654–1655, 1654f, 1656f
physiology of, 1656
for sacral lateral branch, 1663–1664
for third occipital nerve, 1662–1663, 1663f
for thoracic facet syndrome, 1188
for trigeminal neuralgia, 1115–1116, 1656
for trigeminal neuralgia, 1115, 1653
Neuroma, 1668
interdigital (Morton’s), 1224–1225, 1225f, 1670–1671
Neuroma relocation surgery, 1669–1672

5719
Neuromatrix, 79, 144, 147, 1492, 1492t
imaging of, 268, 268f
in phantom pain, 364
Neuromodulation. See specific stimulation modalities and
neuromodulating drugs
Neuromuscular control, 1482–1483
Neuromuscular junction, 507–508, 507f
Neuromuscular training, 1498
Neuron(s)
characterization of, methods, 38–39
Class 1, 42
Class 2, 42–43
Class 3, 42–43
inhibition of, 42–43
intraspinal pathways of, 43
neurochemistry of, 45–50
nociceptive, functional characterization of, 42–43
ON, OFF, and NEUTRAL, 57–58
parasympathetic, 111, 112f
postganglionic, 110–111, 111f
parasympathetic, 111, 113f
sympathetic, 113–114, 113f
postsynaptic dorsal column, 45
preganglionic, 110, 111f, 1148–1150, 1155f
parasympathetic, 111, 113f
sympathetic, 112–113, 113f
second-order, 26, 38–39 (See also Second-order neurons)
site of projection, classification according to, 43
spinal laminae, 39–42, 107
spinomesencephalic, features of, 45
spinoreticular, features of, 44–45
spinothalamic tract
functional characterization of, 44, 107
laminar distribution of, 43–44, 107
wide-dynamic range, 42–43, 107

5720
Neuropathic pain, 59, 329, 566, 1359
afferent contributions to, 34b
arm and neck, 1160, 1163
assessment of, 278–285, 290, 330
burn injury and, 900
cancer-related, 603, 625–626, 628, 653–661
chemotherapy and, 635, 635t, 659–660, 660t, 685–686, 689, 751
in children, 796, 799
diagnosis of, 613–614, 615t, 623–625
etiology of, 626, 626t
in head and neck cancer, 733
imaging findings in, 625, 626f
management of, 685–686, 689
postsurgical, 657–658
presenting complaint in, 609
progression of, 608
referred, 602
secondary to cranial nerve pathology, 653–657
secondary to therapeutic interventions, 657–661
causes of (examples), 1359, 1359t
central, 396–409 (See also Central pain)
chest wall, 1180, 1180t, 1184–1186, 1185t, 1196t–1197t
classification of, 16
definition of, 14, 626
dorsal rhizotomy or ganglionectomy for, 1679
DREZ lesioning for, 1698–1700
electrodiagnostic tests in, 250, 330
epidemiology of, 1359
in failed back surgery, 1290, 1290t, 1291t, 1292, 1295
history of, 228–229
in HIV/AIDS, 992–993, 992f
nerve entrapment releases for, 1668, 1672–1678
neurostimulation for, 1668
nonpharmacologic strategies for, 1375
pain diagram in, 228–229, 229f

5721
pathophysiology of, 1668–1669
pelvic, 1089–1090
peripheral neurectomy for, 1670–1671
pharmacotherapy for, 336–338, 400–403, 1359–1381
acetaminophen, 1367
adjuvant analgesics, 685–686
α2δ ligands, 336–337, 1374
antidepressants, 336, 337, 400–402, 686t, 1359–1362, 1360t, 1361t
antiepileptic drugs, 336–337, 1362–1366, 1363t–1365t
cannabinoids, 337, 1369–1370, 1371t
capsaicin, 337–338, 686t, 1369, 1370t
drug combinations, 1370–1374, 1372t–1373t
drug recommendations (strong or weak), 686t
evidence-based recommendations for, 1374–1375
future drugs, 1374
general principles of, 336
intrathecal, 1375
intravenous lidocaine, 1367, 1387–1388
NMDA receptor antagonists, 1367, 1368t
NSAIDs, 1369
opioid analgesics, 336, 337, 592, 686t, 689, 1366–1367, 1366t
principles of, 338
selective serotonin reuptake inhibitors, 1359, 1360t, 1361t, 1362
serotonin and norepinephrine reuptake inhibitors, 336–337, 400–402,
686t, 1359, 1360t, 1361–1362, 1361t
sodium channel blockers, 1367, 1368t, 1374
tapentadol, 336, 337, 1366t, 1367
topical agents, 337–338, 1369, 1370t
tramadol, 336, 337, 1366t, 1367
plasticity in, 72
quality or description of, 1359
quantitative sensory testing in, 235–236, 330, 1359
in sickle cell disease, 959, 960t, 972
after spinal cord injury, 110, 398, 581, 581t, 585–587, 585f
algorithm for assessing, 587f

5722
 antidepressants for, 591
antiepileptic drugs for, 590–591
at- and below-level spinal cord, 585–587, 585f, 586f
cannabinoids for, 592
combined drug therapy for, 592
group therapy for, 1444t
local anesthetics for, 591
management of, 590–593
NMDA receptor antagonists for, 591–592
opioids for, 592
spinal drug administration for, 592–593
worsening, scenarios of, 585–586, 586f, 586t
spinal cord stimulation for, 404, 1295, 1578
treatment principles in, 336
visceral, 751–752
Neuropathic Pain Diagnostic Questionnaire (DN4), 278–279, 290, 396
Neuropathic Pain Questionnaire (NPQ), 396, 397
Neuropathic Pain Research Consortium (NPRC), 330
Neuropathic Pain Scale (NPS), 279, 281, 285
Neuropathic Pain Special Interest Group (NeuPSIG), 400, 1374
Neuropathic Pain Symptom Inventory (NPSI), 279, 280–281, 285, 397
Neuropathy(ies). See also specific types
chemotherapy-induced, 659–660, 660t
classification of, 329–330
definition of, 14
distribution of symptoms and signs in, 329
electrodiagnostic tests in, 249, 330
evaluation and diagnosis of, 329–330
hereditary, 332–333
history, examination, and diagnostic studies in, 330
in HIV/AIDS, 987–988
infectious causes of, 331, 988t
locus of pathology in, 329, 330
magnetic resonance neurography of, 262–264, 265f–266f
metabolic causes of, 331

5723
 modalities affected in, 329–330
nutritional, 331–332
pain as symptom in, 329, 330
painful, 329–340 (See also Neuropathic pain)
in HIV/AIDS, 987–989, 988t
treatment of, 336–338
unresolved questions in, 338
paraneoplastic, 656–657
postsurgical inflammatory, 887
small fiber, 329, 330, 531
time course of, 329
NeuroPEN, 235–236
Neuropeptide Y, 419
Neuropeptides
in acute pain, 827
in autonomic nervous system, 118
in cutaneous sensation, 543
in myofascial pain (trigger points), 511
in opioid-induced hyperalgesia, 457–458
in spinal nociceptive processing, 47t, 48, 49
Neurosclerosis, for residual limb pain, 368
Neurostimulation. See also specific modalities
for cluster headache, 1027
for fibromyalgia, 536t, 538
for migraine, 1023, 1023t, 1024
for neuropathic pain, 1668
for paroxysmal hemicrania, 1027
for spinal cord injury, 593
Neurotensin, 47t, 49
Neurotic reactions, 318
Neurotransmitters, 45–50, 46t–47t
in acute pain, 827
in autonomic nervous system, 118
colocalization of, 48
in descending systems, 49, 55, 57

5724
 in emotion, 414, 414f
in fibromyalgia, 530, 530t
from glia or unknown sources, 49–50
from interneurons, 48–49
in nociceptive modulation, 55, 55t, 57, 60
from primary afferents, 45–48
release of, 29f, 31–32
in spinal cord stimulation, 1571–1572, 1572f
in stress-induced analgesia and hyperalgesia, 59
from supraspinal sources, 49
Neurovascular disease, cutaneous, 559–560
erythromelalgia, 559
Fabry’s disease, 559–560
sensory mononeuropathies, 559
Neurovascular headache, 1019
Neutral (NEUTRAL) neurons, 57–58
Nevada, addiction-related terminology in, 183t
Nevirapine, and Stevens-Johnson/TEN syndrome, 556
New clinical techniques, training in, 1755–1756, 1757t
New daily persistent headache (NDPH), 1028, 1029–1031
clinical presentation of, 1029
CSF-associated, 1030–1031
differential diagnosis of, 1029t
posttraumatic, 1031
primary, 1029–1030, 1029t
secondary, 1029t, 1030
New drug application (NDA), 175, 1313, 1314
New York, physician-assisted death in, 201–202
New Zealand
pain medicine in, 1754, 1755
topical NSAIDs in, 1319t
NEXUS criteria, for radiologic evaluation of neck, 1168, 1168t
NGC. See Nucleus gigantocellularis
NGCα. See Nucleus reticularis gigantocellularis pars alpha
NGF. See Nerve growth factor

5725
NHANES. See National Health and Nutrition Examination Survey
NHIS. See National Health Interview Study
Nicotinamide, for bullous pemphigoid, 558
Nicotine, 297
Niemann, Albert, 8
Nifedipine, 353, 1052, 1071
NIH. See National Institutes of Health
Nikolsky sign, 556, 557
Nimodipine, for noncardiac chest pain, 1052
NIRS. See Near-infrared spectroscopy
Nisoldipine, for noncardiac chest pain, 1052
Nitrates, for noncardiac chest pain, 1052
Nitric oxide, 47t
for acute chest syndrome, 966
in cancer pain, 732–733
intrathecal, 1628–1629
in stress, 419–420
Nitroglycerin, for noncardiac chest pain, 1052
Nitrous oxide
for burn pain, 902
for cancer pain in children, 794
NLP. See Neurolinguistic programming
NMDA receptor(s), 45–47, 46t, 107
in acute pain, 827, 830
in cancer pain, 732–733
in central sensitization, 53
in C-fiber wind-up, 53
in hyperalgesia, 58
in opioid-induced hyperalgesia, 59, 457, 458f
in pelvic pain, male, 1100
in phantom pain, 364
in spinal cord injury, 110
NMDA receptor antagonists. See also Ketamine; Methadone
for acute pain, 830
for bone pain in cancer, 747

5726
 for cancer pain, 757
for complex regional pain syndrome, 352–353
for elderly patients, 934
for fibromyalgia, 538
intrathecal, 1627
for neuropathic pain, 1367, 1368t
for phantom pain, 366
for postherpetic neuralgia, 388
for spinal cord injury pain, 591–592
NNT. See Number needed to treat
Nocardia asteroides, in HIV/AIDS, 987
Nocebo, 14, 144, 1257
Nociceptin, 46t, 48–49
Nociceptin/orphanin FQ (N/OFQ) peptide receptor, 48–49
Nociception, 5–6
definition of, 14
in Loeser’s model of pain, 85
in neonates, 809
spinal processing in (See Spinal nociceptive processing)
supraspinal mechanisms of, 62–75
visceral, 1065–1066
Nociceptive flexion reflex, 1423
Nociceptive pain, 16, 103, 566
analgesic adjuvants for, 853
cancer-related, 613–614, 615t, 625–626, 636
dorsal rhizotomy or ganglionectomy for, 1679
in HIV/AIDS, 992–993, 992f
peripheral neurectomy for, 1671–1672
in sickle cell disease, 959, 960t
spinal cord injury and, 581, 581t, 582–584
algorithm for assessing, 585f
management of, 588–590
musculoskeletal, 582–584, 585f, 587f, 588–590
Nociceptive system
central (CNS), 106–110

5727
 functional neuroanatomy of, 103–122
nerve supply to body structures, 115t–117t
peripheral
cutaneous fields in, 103, 105f
dermatomes in, 103, 104f
organization of, 103–106
somatic v. visceral pain in, 103–106, 106t
structures of pain sensation in, 106
Nociceptive-specific neurons, 42
Nociceptors, 6, 566
action potential generation in, 26, 30–31
anatomy of, 26
characteristics of, 26–32
chemical sensitivity of, 24
clinical implications of function, 33–34
definition of, 14, 24
distribution in body, 24
electrophysiologic properties of, 30
functional characterization of, 24
generator potential in, 26, 30
low threshold, 24
mechanical sensitivity of, 24
mechanically insensitive, 24
methods of characterizing, 38–39
microneurography of, 25b
muscle, activation of, 508–509
polymodal, 24
putative, identification of, 25–26
sensitization of, 32–33
Sherrington’s study of, 24
signal transduction in, 26–30, 27f–29f
silent or sleeping, 24
thermal sensitivity of, 24
Noel, Walter Clement, 955
Nonadherence, 157, 236, 1724

5728
Nonanatomic pain, medical evaluation of, 316–317
Nonbeneficial treatment
checklist on, 168, 168t
clinical context of conflict over, 166
differential diagnosis of conflict over, 166–167, 167t
ethical basis of conflict over, 166
information about, 167, 167f
intractable conflicts over, 167, 167t
resolvable conflicts over, 167, 167t
responding to demands for, 166–168
Noncardiac chest pain (NCCP), 525, 534, 1034–1061
autonomic activity in, altered, 1041
cardiologist v. primary care management of, 1034, 1036f
definition of, 1034
diagnosis of, 1041–1046
ambulatory 24-hour esophageal pH monitoring in, 1037, 1038, 1043
barium esophagram in, 1042
cardiology evaluation in, 1041–1042
esophageal manometry in, 1038, 1038f, 1045–1046
multichannel intraluminal impedance in, 1045
proton pump inhibitor test in, 1043–1044
provocative testing in, 1046
upper endoscopy in, 1042–1043, 1042t
wireless pH system in, 1043
differential diagnosis of, 1193t–1202t
epidemiology of, 1034–1035
esophageal dysmotility in, 1038–1039, 1038f, 1045
esophageal hypersensitivity in, 1037, 1039–1040
esophageal origin of, 1034, 1035t, 1195t–1196t
esophageal sensory testing in, 1046–1050
acid perfusion (Bernstein) test in, 1047–1048
balloon distention protocol in, 1039–1040, 1039f, 1046–1050
brain imaging in, 1050
electrical stimulation in, 1048
evoked potentials in, 1050

5729
 intraluminal ultrasonography in, 1037–1038, 1048
pitfalls in study design, 1050
etiologies of, 1034, 1035f, 1035t
gender differences in, 1034, 1041
GERD, 1034, 1036–1038, 1042–1045, 1051, 1054–1055, 1195t
group therapy for, 1448t
health care costs of, 1035
linked angina with, 1038
management algorithm for, 1056f
natural history of, 1035–1036
non-GERD, 1034, 1051–1052
pain thresholds in, 1037, 1037f, 1039–1040, 1039f, 1040f
pathophysiology of, 1036–1041
psychological comorbidity in, 1041, 1047
psychological evaluation in, 1050
psychological interventions for, 1055
referrals for, 1034–1035
Rome IV Committee criteria for, 1034, 1035t
sustained esophageal contractions in, 1039, 1047
treatment of, 1051–1056
antidepressants for, 1052–1053, 1052t
botulinum toxin for, 1054, 1055f
endoscopic and surgical, 1054–1055
future research and therapies in, 1055–1056
general plan for, 1052t
GERD-related, 1051, 1052t, 1054–1055
hypnotherapy in, 1055, 1055f
Johrei therapy in, 1055
muscle relaxants for, 1051–1052
non-GERD-related, 1051–1052, 1052t
pain modulators for, 1051–1053
Non-communicating Children’s Pain Checklist, 822
Noncontrast low-frequency ultrasound (NCLFUS), 1526
Nongonococcal bacterial arthritis, 500–501
Non-Hodgkin lymphoma, 643

5730
 chemotherapy for, 780
epidemiology of, 622f
superior vena cava syndrome in, 1184
Noninferiority trials, 132
Nonmaleficence, 151
Nonresponder neurons, 42
Nonsteroidal anti-inflammatory drugs (NSAIDs), 1315–1332. See also
specific drugs
for abdominal pain, 1069, 1071
for acute chest syndrome, 966
for acute pain, 829–830
in ambulatory surgical patients, 839
in opioid-tolerant patients, 840
in war trauma, 838
agents withdrawn from market, 1315
AHA discouragement of use, 1314
allergy and hypersensitivity, 1326–1327
for ankylosing spondylitis, 494
for bone pain, 686
for breast pain, 1190
for burn pain, 902
for calcium pyrophosphate deposition disease, 497
for cancer pain, 681, 686
for cancer pain in children, 793, 797–798
cardiovascular effects of, 1324–1326, 1325f, 1325t, 1326f
central nervous system effects of, 1328
for children, 811, 812t, 916, 917
for headache, 922
combination medications, 1323–1324
commercially available in U.S., 1315, 1316t
for complex regional pain syndrome, 352
contraindicated in pregnancy, 1081
for costochondritis, 1189
for costovertebral arthritis, 1188
for diffuse idiopathic skeletal hyperostosis, 1188

5731
for dysmenorrhea, 1069, 1071, 1083
for elderly patients, 931–932
in emergency department, 1775, 1776t
for endometriosis, 1086–1087
for erythema nodosum, 554
for erythromelalgia, 559
for failed back surgery, 1295
FDA warning on, 1324–1325, 1325t
for fibromyalgia, 537t, 538
gastric protection with, 931, 1327
gastrointestinal toxicity of, 1327, 1328f
for gout, 500, 1224
hematologic effects of, 1327
hepatic toxicity of, 1328
for herpes zoster, 378, 379t
for hidradenitis suppurativa, 555
history of, 1315
for HIV pain, 993
for IBD-associated arthritis, 496
injectable, 1318
in intensive care unit, 1783
intranasal, 1318
for leukocytoclastic vasculitis, 546
for low back pain, 1254, 1271, 1278, 1355
for male pelvic pain, 1104
mechanism of action, 1315–1317
central sites of, 1315
COX-1 and COX-2 selectivity, 1315–1317, 1317f, 1324f
peripheral sites of, 1315
for migraine, 991t, 1023–1024, 1024t, 1025
for myofascial pain, 1190
for neuropathic pain, 1369
opioid analgesics concurrent with, 1311–1313
oral, 1317–1318
for oral mucositis, 738

5732
 for osteoarthritis, 490
for patients with substance use disorder, 463
pharmacokinetics of, 1317–1318
absorption, 1317–1318
distribution, 1318
elimination, 1318
pathophysiologic conditions affecting, 1318
for polyarteritis nodosa, 547
for prostate pain syndrome, 1104
for psoriatic arthritis, 496
for reactive arthritis, 495
for relapsing polychondritis, 558
renal toxicity of, 1327–1328
for rheumatoid arthritis, 491
for rib fracture pain, 1188, 1189
for sickle cell disease pain, 973
side effects of, 1324–1329
for spinal cord injury pain, 589
for sternoclavicular joint arthritis, 1189
surgical complications with, 1329
for tension-type headache, 1025, 1133
for thoracic facet syndrome, 1188
topical, 1318, 1319t, 1356–1357
for xiphoidalgia, 1190
Nonulcer dyspepsia, 525
Nonverbal Pain Scale (NVPS), 1784
Nonverbal patients, pain assessment in, 1734, 1734t
Noradrenaline. See Norepinephrine
Noradrenergic stress response hypothesis, 415
Norepinephrine, 46t, 49
in anger (negative emotions), 1394
in autonomic nervous system, 118
in brainstem, 63
in cancer pain, 732–733
in childbirth, 942

5733
 in depression, 436
in descending modulation of pain, 54, 55, 55t, 56, 57, 60
in emotion and noxious signaling, 412–417, 414, 414f
in myofascial pain (trigger points), 511–512
in stress, 419
in stress-induced analgesia and hyperalgesia, 59
in vigilance network, 70
North American Spine Society, 1290
North Carolina
addiction-related terminology in, 183t
civil litigation over pain management in, 196
Nortriptyline
for abdominal pain, 1070
for central pain, 400
for children, 917
for depression, 439
for fibromyalgia, 535, 536t,
for herpes zoster, 378
for HIV pain, 994t, 996–997
for migraine, 990t
for migraine prevention, 1023t
for neuropathic pain, 400, 1359–1361, 1360t, 1361t
for noncardiac chest pain, 1053
for postherpetic neuralgia, 384t, 386, 388
Not Dead Yet, 155
Notalgia paresthetica, 559
Novaco Anger Scale (NAS), 1398t, 1399
Novaco Anger Scale and Provocation Inventory (NAS-PI), 1398t, 1399
Noxious signaling, 413–417, 414f
HPA axis in, 413–414, 416–417, 416f
locus coeruleus and dorsal noradrenergic bundle in, 414–415, 414f
ventral noradrenergic bundle in, 414, 414f, 416–417, 416f
Noxious stimuli, 5–6, 14, 24, 566
in depression–pain association, 435–436
Noxious-level stimulation, 1526–1527

5734
NpGC. See Nucleus paragigantocellularis
NPQ. See Neuropathic Pain Questionnaire
NPRC. See Neuropathic Pain Research Consortium
NPS. See National Pain Strategy
NPSI. See Neuropathic Pain Symptom Inventory
NRM. See Nucleus raphe magnus
NRS. See Numerical Rating Scale
NS1209, for cancer pain, 758
NSAIDs. See Nonsteroidal anti-inflammatory drugs
nSTT. See Neospinothalamic tract
NTS. See Nucleus tractus solitarius
N-type calcium channels, 50
Nucleoside analogues, for herpes zoster, 377–378, 377t
Nucleus accumbens, 64, 1002–1003, 1003f
motivation and, 1470–1471
opioid analgesics and, 1337
Nucleus caudalis ablation, 1704–1705
Nucleus gigantocellularis (NGC), 54–56, 55t
Nucleus paragigantocellularis (NpGC), 54–55, 55t
Nucleus proprius, 41
Nucleus pulposus, 1138–1139
Nucleus raphe magnus (NRM), 54–56, 55t, 109
Nucleus reticularis gigantocellularis pars alpha (NGCα), 54–56, 55t
Nucleus tractus solitarius (NTS), 64
in descending modulation of pain, 55–56, 55t
in pain–ANS interaction, 114
in somatic v. visceral pain, 106
Nuland, Sherwin, 152, 1751
Null hypothesis, 132
Number needed to treat (NNT), 336, 400
Numerical Rating Scale (NRS), 228, 229, 276, 276f, 288, 289, 321
for cancer pain, 636
for central pain states, 397
for chronic pain in children, 914
for dying patients, 1733

5735
 for emergency department assessment, 1771–1772
for HIV pain, 992
for low back pain, 1250
Nummular headache, 1122–1123
NUPRIN Pain Report, 91
Nuremberg Code, 154
Nurse-controlled analgesia (NCA), for children, 816
Nurses, 1712
advanced practice, 1711
Nutcracker esophagus, 1038, 1038f, 1040, 1052
Nutrition
complex regional pain syndrome and, 344–345
myofascial pain and, 514–515
Nutritional neuropathies, 331–332
NVPS. See Nonverbal Pain Scale

O
OA. See Osteoarthritis
Obesity
acute pain management in, 841
definition of, 841
nerve entrapment in, 1210
surgery for, neuromuscular manifestations after, 332
Observation
in cancer pain, pediatric, 790
in neck and arm pain, 1162
in pain assessment, 289, 321–322
in physical examination, 233
in psychology evaluation, 298
Observational (social) learning, 83, 426, 428
Obsessive-compulsive disorder, 440
Obstetric pain, 940–954
analgesia effects of labor progress, 951
combined spinal-epidural analgesia for, 946, 948–949
advantages and disadvantages of, 947t, 948
complications of, 949

5736
 drugs for initiating, 948–949, 948t
needle-through-needle technique for, 948
side effects of, 949
continuous spinal analgesia for, 947t, 949
epidural analgesia for, 940, 946–948
advantages and disadvantages of, 947t
caudal, 947t, 949–950
complications of, 949
drugs for initiating, 947–948, 947t
dural puncture, 949
maintenance of, 949, 949t
onset of, 947
patient-controlled, 949
side effects of, 949
historical perspective on, 940
lumbar sympathetic block for, 940, 941, 951
maternal and fetal effects of, 942, 942f
measurement of, 940, 941f
mechanisms and pathways of, 940–941, 941f
neuraxial analgesia for, 940, 946–950
advantages and disadvantages of specific techniques, 947t
complications of, 949
contraindications to, 946
side effects of, 949
nonpharmacologic methods for, 945–946
paracervical block for, 950
perineal infiltration for, 951
physical factors in, 941–942
physiologic changes of pregnancy and, 942–945
anesthetic implications of, 943t, 944
cardiovascular, 943–944, 943f, 943t, 944f
central nervous system, 943t, 944
pharmacokinetics, 943t, 945
respiratory, 943, 943t
transfer of drugs across placenta, 945

5737
 psychological factors in, 941, 942
pudendal block for, 940, 951
regional analgesia for, 940
single-shot spinal analgesia for, 947t, 949
systemic analgesia for, 946
Obstetric-related lumbosacral plexopathy, 1208, 1209f
Obstructive sleep apnea, acute pain management in patients with, 841
Obturator nerve, 868–869, 869f
anatomy of, 1205, 1206f, 1214, 1214f
in pelvic pain, 1101, 1102
Obturator nerve block, 876–877
complications of, 877
indications for, 876–877
landmarks for, 876–877
ultrasound guidance for, 877, 877f
Obturator nerve entrapment, 1214–1215
diagnosis of, 1215
etiology of, 1214
symptoms and signs of, 1214–1215
treatment of, 1215
Occipital condyle syndrome, 653
Occipital lobe, 62f
Occipital nerve block, 1134, 1598f, 1605, 1607
Occipital nerve stimulation, 1027, 1565–1566
Occipital neuralgia, 1485
diagnostic nerve block in, 1598f, 1605
dorsal rhizotomy or ganglionectomy for, 1680
inspection and palpation in, 1164
peripheral nerve stimulation for, 1565
Occipital thermal radiofrequency neurotomy, 1239–1240, 1240f, 1662–
1663, 1663f
Occupational therapist, 1712
Occupational therapy, 1498–1499
for complex regional pain syndrome, 350–351
ergonomics in, 1498, 1499t

5738
 functional capacity evaluations in, 1498, 1501–1503
pacing in, 1500, 1500t
in spine clinics, 1719
work rehabilitation in, 1501, 1501t
Ochronosis, 489
O’Connor, Sandra Day, 201
Octreotide, 1054, 1628
Oculomotor nerve, 111, 112f, 1162t
Odic force, 1552
Odontogenic pain, 1130–1131
diagnosis of, 1130, 1131t
trigeminal neuralgia v., 1113
Odontoid process, 1138, 1139f, 1140f, 1142f
OFF neurons, 57–58
Office of National Drug Control Policy (ONDCP), 187
Off-label uses, 1313
OIH. See Opioid-induced hyperalgesia
Oklahoma, addiction-related terminology in, 183t
Olanzapine, for nausea/vomiting in cancer therapy, 684
OLBPQ. See Oswestry Low Back Pain Disability Questionnaire
Older person. See Elderly
Olfactory nerve, 1162t
Oligoanalgesia, in emergency department, 1772, 1772t
Olivospinal tract, 40f
Omeprazole
for gastric protection with NSAIDs, 1327
for GERD-related chest pain, 1051
for proton pump inhibitor test, 1044
OMPFC. See Orbitofrontal and medial prefrontal cortex
On (ON) neurons, 57–58
Oncology. See also Cancer; Cancer pain
integrative, 701–702
substance abuse in, 699–700, 700t
Ondansetron
for migraine, 1024

5739
 for nausea/vomiting in cancer therapy, 684, 684t
ONDCP. See Office of National Drug Control Policy
Onset of pain (O), 228, 228f
in cancer, 608, 608t, 663
in neck and arm, 1159, 1160
Onychocryptosis, 1226, 1226f
Open kinetic chain, 1498t
Open therapy groups, 1464
Open-ended questions, 1472, 1473t
Operant conditioning, 82–83, 425–426
for burn pain, 904–905
and chronic pain, 427
in depression, 437
for low back pain, 1541
and pain, 426–427
in pain treatment outcome, 445
for rehabilitation, 1497
for substance use disorder, 1513
Operant pain, 1202t
Ophthalmoplegia, painful, 1113
Ophthalmoplegic migraine, 1113
Opiate, definition of, 1333
Opioid(s)
definition of, 1333
endogenous, 48–49, 1336, 1571
in acute pain, 827
in anger, 1394–1395, 1397–1398
in descending modulation of pain, 55, 55t, 60
in stress-induced analgesia and hyperalgesia, 59
Opioid abuse or misuse, 173, 187, 297–298. See also Substance abuse;
Substance use disorder
aberrant behavior in, 1002t, 1004–1005, 1012, 1013–1014, 1517, 1517t
addiction in, 1338, 1340–1341
continuum approach to, 1004, 1004f
science of, 1002–1003, 1003f

5740
 assessment for, 227, 231–232, 297–298, 1006–1007, 1006t
in cancer, 601, 610, 610t, 617–618, 699–700, 700t
definitions in, 1772–1773
dependence in, 231–232, 1001, 1338, 1340, 1772
in emergency department, 1772–1775
ethnic differences in, 95
fear of, as barrier to use, 216, 1725–1726
fentanyl, 694–695
formulations for deterring, 1346, 1349t
gender differences in, 93
historical perspective on, 1516–1518
in HIV patients, 997
neonatal effects of, 1341
pain medicine perspective on, 1516–1519
risk factors for, 700, 700t
in spine surgery candidates, 1302
terminating opioid therapy in, 1005–1006, 1017
Opioid agonists, 1334t–1335t, 1336. See also Opioid analgesics
Opioid agreements (contracts), 156–157, 617, 1007, 1008t
Opioid analgesics, 1333–1351. See also specific analgesics
for abdominal pain, 1069
abuse-deterrent formulations of, 1346, 1349t
for acute pain, 828–829
in ambulatory surgical patients, 839
continuous epidural, 833–836, 833t
in elderly, 839
intra-articular, 837
intravenous patient-controlled, 832–833, 832t
in opioid-tolerant patients, 840–841
patient-controlled epidural, 835, 836t
side effects in neuraxial administration, 834–835
single-dose neuraxial, 833, 833t
subarachnoid, 851–852
in war trauma, 838
adequate availability of, 206–207

5741
adjuvant, 853–854
administration of, 828–829, 1341–1343 (See also specific routes)
alternative noninvasive routes of, 1342
end-of-life, 1735–1736
epidural, 1343, 1343f, 1736
intracerebroventricular, 699
intramuscular, 828–829
intrathecal, 1343
intravenous, 698–699, 828–829, 901–902, 1736
intraventricular, 1343
oral, 828–829, 901–902, 1341–1342
parenteral, 698–699, 828–829, 1342, 1736
pediatric, 815–816
rectal, 1342–1343, 1342t, 1735
subcutaneous, 698–699, 1342, 1736
sublingual, 1342–1343, 1735
topical, 1736
transdermal, 1342, 1736
transmucosal, 901–902, 1342
affordability of, 218–219
aggressive, in dying, 168–169
alternatives to, 1311, 1311t
analgesia from, 1336–1337
antiretroviral therapy and, 995, 995t
antitussive effect of, 1338
barriers to safe and effective, 172–173, 215–221, 216t
benzodiazepine interaction with, 439, 441, 1337–1338
biased ligands, 1350
for burn pain, 901–902, 903
for cancer pain, 205, 676–677, 682–684, 687–700
active treatment v. chronic pain, 689
bone, 747
buprenorphine, 690t, 695
in children, 795–796, 798–799, 821–822
codeine, 695–696

5742
 diversion of, 619
drugs not recommended, 696
in elderly patients, 689
extended-release, 690, 690t
fentanyl, 689, 690, 690t, 693–695, 698–699
history of abuse and, 617–618
hydrocodone, 690t, 695
hydromorphone, 690t, 691–692, 698–699, 821–822
intracerebroventricular, 699
levorphanol, 692–693
methadone, 689, 692, 698–699, 821–822
misuse or abuse of, 699–700, 700t
morphine, 689, 690t, 691, 698–699, 821–822
mucositis-related, 738, 795–796
newer derivatives, 758–759
oxycodone, 689, 690t, 691
oxymorphone, 691
parenteral, 698–699
pediatric, 821–822
risk evaluation and monitoring for, 665, 667t, 700, 700t
rotation of, 698, 698t, 799
selection of therapy, 687–690
short- v. long-acting, 689–690, 696
side effects of, 617, 682–683, 696–697, 697t
tapentadol, 690t, 696
tolerance and hyperalgesia with, 690–691
tramadol, 696
transdermal, 690, 690t
central nervous system effects of, 1336–1341
depressive, 1336–1338
excitatory, 1338
for central pain, 401t, 402f, 403
for childbirth pain
combined spinal-epidural, 948–949, 948t
epidural, 947t, 948

5743
 parenteral, 946
patient-controlled intravenous, 946
for children, 812–817, 916, 917
administration of, 815–816
for cancer pain, 795–796, 798–799, 821–822
codeine, 812–813, 814t
continuous infusions of, 815
dosing guidelines for, 814t
fentanyl, 814–815, 814t
hydromorphone, 813, 814t, 821–822
intermittent intravenous bolus dosing of, 815
meperidine, 814t, 815
methadone, 813–814, 814t, 821–822
morphine, 813, 814t, 821–822
ontogeny of action, 812–813
oxycodone, 813, 814t, 821–822
side effects of, 798–799, 816–817, 817t
tramadol, 813
classification of
based on opioid agonist or antagonist activity, 1336
based on receptor interactions, 1333–1336
cognitive and motor effects of, 697–698
commonly used, 1334t–1335t
for complex regional pain syndrome, 352
consumption of
disparities in, 207–209, 208t
trends in, 208–215, 209f, 211f–214f
distribution system for, 217–218, 218f
and doctor–patient relationship, 477
dose conversion and calculators, 829, 829t
dose increases for, 1312
driving ability affected by, 697–698, 698t
for elderly patients, 931, 932–933
potential safety concerns with, 932–933
product selection and use, 933

5744
in emergency department, 1775–1776
emergency department use of, 1771
as essential medicines, 206
ethnic differences in, 95
for failed back surgery, 1295
for fibromyalgia, 537–538, 537t
future of, 1346–1350
gender differences in, 93, 140, 842–843
half-life of, 1340, 1340t
for herpes zoster, 378, 379t
for HIV pain, 205, 993–995, 994t
hypothalamic effects of, 1338
increased requests for, 458, 459f
individual differences in response, 90, 1312
in intensive care unit, 1782, 1784, 1785–1786
intrathecal, 714–715, 714t, 1343, 1624–1625, 1624f, 1625t, 1637–1640
for acute pain, 851–852
dose and concentration limitations for, 1638, 1638t
in end-of-life care, 1736
for neuropathic pain, 1375
side effects of, 1637
for spinal cord injury pain, 592
tolerance in, 1637–1638
law and policy on
additional U.S., considering, 185–186
balance principle in, 174, 181, 184, 187–188, 207, 207t, 1001
CDC guidelines, 1008, 1504, 1724, 1744, 1747, 1764
Chicago code of conduct, 199
classification schedules, 176
comprehensive systems approach in, 176
DEA discouragement of use, 1314
diversion considerations in, 186–187
future of pain medicine and, 1793–1794
guidelines for chronic use, 181, 1313, 1314t
international access, 205–224

5745
 international treaties, 173–175, 206–208
litigation over, 193–204
policies governing use, 173
UN recommendations on, 219–220
U.S. federal law, 175–180
U.S. state laws, 180–185
lipid solubility of, 833, 834, 853, 931
long-acting, 175–176, 689–690, 696, 1342
for low back pain, 1271
for male pelvic pain, 1105
functional effects of, 1103t
in prostate pain syndrome, 1104
in scrotal/testicular/epididymal pain syndromes, 1104
mood effects of, 1337
morphine equivalent daily dose of, 186, 310
multiple-copy prescription forms for, 174, 181
nausea and vomiting with, 816–817, 817t, 1337
neonatal effects of, 1341
neuraxial, 853
for neuropathic pain, 403, 1366–1367, 1366t
in cancer, 689
in painful neuropathies, 336, 337
in spinal cord injury, 592
new ethic of pain relief, 151, 156–157
NSAIDs concurrent with, 1311–1313
patient and family perceptions about, 172
perineural, 853–854
peripheral effects of, 1341
for phantom pain, 365–366
pharmacodynamics of, 1336
pharmacokinetics of
hepatic dysfunction and, 688–689, 689t
renal dysfunction and, 687–688, 688t
for postherpetic neuralgia, 385t, 386–387, 1118, 1186
for pregnant patients, 1081, 1341

5746
primary care providers and, 1724
professional barriers to use, 154, 215–216, 676
pruritus with, 816–817, 817t, 1341
pupil constriction with, 1338
rehabilitation and management of, 1503–1504, 1504t
respiratory depression with, 1337–1338
for rib fracture pain, 1188
risk mitigation strategies for, 465, 465t
rotation of, 698, 698t, 799, 1312, 1339–1340, 1349, 1737
sedation with, 1337
selection of agent, 1346
short-acting, 689–690, 696
for sickle cell disease pain, 973
in acute chest syndrome, 966
in avascular necrosis, 970
in priapism, 969
side effects of, 1337–1343
in cancer pain, 682–683, 696–697, 697t
in children, 798–799, 816–817, 817t
concerns, as barrier to use, 216
in intrathecal delivery, 1637
in neuraxial administration, 834–835
symptom control v., 1312
smooth muscle and cardiovascular effects of, 1341, 1344
for spinal cord injury pain, 589, 592
stopping
case vignettes and analysis, 1745–1749
empathy and, 1749
Erikson’s Golden Rule and, 1744, 1745t
ethics in, 1744–1750
guideline changes and, 1747
monitoring issues and, 1747–1748
mutuality and, 1745, 1748–1749
narrative medicine and, 1749
trust and, 1744–1745, 1748–1749

5747
 synergism and potentiation of, 1312–1313
tapering of, 469, 1005, 1017, 1340
trial of, 1007–1008, 1013
urine testing for, 1016, 1016f, 1509, 1509t, 1518
Opioid antagonists, 1334t, 1336. See also Opioid analgesics
Opioid deficit hypothesis, 1397–1398
Opioid dependence, 1001, 1338, 1340. See also Substance use disorder
assessment for, 231–232
neonatal, 1341
in rehabilitation, managing, 1503–1504, 1504t
spectrum of, 231
Opioid epidemic, 1517
Opioid maintenance treatment, 178, 1001, 1008–1009, 1511–1516
and hyperalgesia, 458–459
Opioid metabolites, 1347t–1348t
Opioid receptors, 48, 55, 1333–1336
in acute pain, 827
in cancer pain, 758
delta (δ), 48, 1333
in depression–pain association, 436
in fibromyalgia, 530
in gastrointestinal function/pain, 1069
in intrathecal drug delivery, 1624
kappa (κ), 48, 1333
mu (μ), 48, 1333–1336, 1335f
in neuraxial analgesia, 853
OPRM1 gene and, 96
in substance use disorder, 455–456
Opioid Risk Tool (ORT), 231, 298, 610, 1006, 1006t
Opioid tolerance, 690–691, 1338–1340, 1772–1773
acute pain management in, 840–841
to analgesia, 1338
associative, 1339
in burn injury, 899
in children, 799

5748
 clinically observable, 1338–1339
to CNS-depressing effects and nausea, 1338–1339
hyperalgesia and, 457
in intrathecal drug delivery, 1637–1638
in opioid use disorder, 456, 1510, 1510t
to opioid-induced constipation, 1338–1339
opioid-sparing strategies to reduce, 1339–1340
pharmacologic, 1339
presurgical prehabilitation program in, 841
proposed mechanisms of, 1339–1340
Opioid treatment program (OTP), 178–179. See also Opioid maintenance
treatment
Opioid use disorder, 1338, 1340–1341. See also Substance use disorder
DSM-5 criteria for, 1510, 1510t
effect on pain, 455–456
genetics of pain and, 456
historical perspective on, 1516–1518
hyperalgesia in, 457–460
pain management in patient with, 453–475
pain medicine perspective on, 1516–1519
pain responses in, 459, 459t
tolerance in, 456
treatment and/or referral for, 1511–1516
Opioid withdrawal, 456–457, 1017, 1340, 1764
in diagnostic criteria, 1510, 1510t
hyperalgesia in, 457
in intrathecal drug delivery, 1639
medically supervised, 1511
Opioid-induced androgen deficiency, 1338
Opioid-induced bowel dysfunction, 682–683, 697t, 1341
in cancer patients, 617
in children, 816–817, 817t
in elderly patients, 933
tolerance to, 1338–1339
treatment of, 683, 1341

5749
 μ-opioid receptors in, 1333–1336
Opioid-induced hyperalgesia (OIH), 59–60, 1339
in cancer pain management, 690–691
in chronic pain patients, 460
clinical evidence of, 458–460
ethics of opioid cessation in, 1745–1747
genetics and, 460
in healthy controls, 459–460
in intrathecal drug delivery, 1626
in maintenance programs, 458–459
mechanisms of, 457–458, 458f
in opioid use disorder, 457–460
in surgical patients, 459
and tolerance, 457
withdrawal, 457
Opioid-induced myoclonus, 1737
Opioid-induced nausea and vomiting, 683–684, 684f
Opioid-sparing strategies, 1339–1340
Opium, 8
OPRM1 gene, 96
Optic nerve, 1162t
Optimism, 77
Oral care, during cancer treatment, 737
Oral contraceptives
for dysmenorrhea, 1083–1084
for endometriosis, 1086t
Oral mucositis, in cancer, 661, 734–739, 754
anti-infective approaches in, 738
in children, 795–796
epidemiology of, 734, 734t
hematopoietic cell transplantation and, 734, 735, 735f, 737, 738, 741,
795
hyposalivation and, 738–739
management of, 736–737, 737t
oral care and oral rinses in, 737

5750
 pain management for, 737–740, 740t
pathogenesis of, 734–735, 734f, 735t, 739, 739f
pediatric, 821
prevention of, 737, 737t, 738–740, 796
radiation therapy and, 735–737, 736f, 754, 796
stepped protocol for, 737
stomatitis v., 754
systemic analgesics for, 738
topical anesthetics and analgesics for, 737
topical antimicrobials for, 738
WHO grades of, 661, 661t, 795
Oral NSAIDs, 1317–1318
Oral opioids, 828–829, 901–902, 1341–1342
Oral rinses, for mucositis prevention, 737
Oral route, for end-of-life drug delivery, 1735
Oral transmucosal fentanyl citrate (OTFC), 1735
Orbital syndrome, 653
Orbitofrontal and medial prefrontal cortex (OMPFC), 68–70, 69f
Oregon, physician-assisted death in, 168, 169, 202
Oregon Board of Medical Examiners v Bilder, 195
Organ dysfunction
in dying
myoclonus with, 1737
pharmacokinetics in, 1736
in sickle cell disease, 969
Orgasmic cephalgia, 1028
Orgone, 1552
Oriental medicine, 1553
Orofacial pain
in cancer, 732, 732t
group therapy for, 1442
Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA),
97
Oropharyngeal pain
in head and neck cancer, 732–743

5751
 in HIV/AIDS, 986
Orphenadrine, 685, 1254, 1352t, 1354
ORT. See Opioid Risk Tool
Orthodromic SNCS, 244, 245f
Osteitis fibrosa cystica, 1251
Osteoarthritis (OA), 487–490
adjuvant analgesics for, 685
arthroscopic findings in, 487, 488f
COX-2 selective NSAIDs for, 490, 1322
epidemiology of, 484, 487
erosive, 489
fibromyalgia with, 527
first metatarsophalangeal joint, 1223, 1223f
group therapy for, 1443t, 1462t
heat therapy for, 1523
hypnosis for, 1431
laboratory findings in, 489
laser therapy for, 1524–1525
pain in
ethnic differences in, 94–95
gender differences in, 92
genetics and, 96
individual differences in, 90
pathophysiology of, 487
pattern recognition in, 486
primary, 487
primary generalized, 487
radiography of, 489, 489f
risk factors for, 487
secondary, 487, 489
symptoms and signs of, 487–489, 488f
topical agents for, 1356–1357
treatment of, 489–490
Osteomyelitis, spinal, MRI of, 261, 261f, 262f
Osteonecrosis. See Avascular necrosis

5752
Osteopathy, 1550–1554
Osteopenia
complex regional pain syndrome and, 344–345
in HIV/AIDS, 987
Osteoporosis
in HIV/AIDS, 987
vertebral fractures in, 1187
Osteoprotegerin (OPG), 745
Oswestry Disability Index, 129, 232, 1288, 1305, 1542
in low back pain, 1286
Oswestry Low Back Pain Disability Questionnaire (OLBPQ), 320, 323
OTFC. See Oral transmucosal fentanyl citrate
Otic ganglion, 111, 112f, 113f
Otilonium bromide, for abdominal pain (IBS), 1071
Ototoxicity, of NSAIDs, 1328
Oucher, 790
Outcome measures, in clinical trials, 128–129, 128t
Outpatient surgical patients, acute pain management in, 839
Ovarian cancer, 639
chemotherapy for, 781
epidemiology of, 639
pain in, 639
abdominopelvic or low back, 639
visceral, 755
Ovarian cyst accident, 1080, 1082
Ovarian hyperstimulation syndrome, 1082–1083, 1083t
Ovarian pain, in cancer, 653
Ovarian remnant syndrome, 1088
Ovarian torsion, 1080
Overdetermination, 146
Overdose, opioid
respiratory depression in, 1337–1338
sedation in, 1337
Overshunting, 257–258, 258f
Overt expressions of pain, 321–322

5753
Ovulation, pain with, 1084
Owens, Bill, 1751–1752
Oxaprozin, 1316t, 1322
Oxcarbazepine
for central pain, 402
for children, 918
for neuropathic pain, 402, 1363t, 1365, 1367
for painful neuropathies, 337
for sensory mononeuropathies, 559
for trigeminal neuralgia, 1113–1115, 1691, 1692
Oxicam derivatives, 1322
Oxycodone (OxyContin), 1334t, 1345
abuse-deterrent formulations of, 1349t
for burn pain, 903
for cancer pain, 689, 690t, 691, 821–822
for cancer pain in children, 798
for children, 813, 814t, 821–822
compliance monitoring of, 1013–1014
consumption trends for, 208
dose conversions of, 829t
for elderly patients, 933
in emergency department, 1775–1776, 1776t
extended-release, 690t
hepatic dysfunction and, 689t
for herpes zoster, 378
for HIV pain, 994t, 995, 996
in intensive care unit, 1787
interaction with antiretroviral therapy, 995, 995t
litigation over, 199
metabolites of, 1347t–1348t
morphine equivalence of, 208
for neuropathic pain, 1366–1367, 1366t
for painful neuropathies, 337
for postherpetic neuralgia, 385t, 386–387
promotion and claims, 130–131, 199, 1517

5754
 rectal, 1342t, 1343
relative efficacy of, 829t
renal dysfunction and, 688t
for sickle cell disease pain, 963
for spinal cord injury pain, 592
urine testing for, 1016, 1016f, 1509, 1509t
Oxygen therapy
for anaphylaxis, 1765
for cluster headache, 1027
Oxymorphone, 1334t, 1345
for cancer pain, 691
dose conversions of, 829t
for HIV pain, 994t
intravenous patient-controlled, 832t
urine testing for, 1016f
Oxyphenbutazone, 1315
Oxytocin, 46t, 49
in nociceptive modulation, 55t
in stress-induced analgesia and hyperalgesia, 59

P
P2X purinoceptor-3 antagonists, for cancer pain, 758
P38 kinase inhibitors, for cancer pain, 758
Pace’s maneuver, 1217
Pacing, 1499, 1499t
PACSLAC. See Pain Assessment Checklist for Seniors with Limited
Ability to Communicate
PAG. See Periaqueductal gray
Paget disease of bone, 1188, 1233
Paget-Schroetter syndrome, 267, 576
Pain. See also specific pain types and topics
biopsychomotor model of, 1490, 1490f
classical conditioning and, 427–428, 427f
construction and modulation of, 417
definition of, 11, 410, 566, 602
as emotional experience, 79, 410

5755
 ethnic differences in, 94–96
as fifth vital sign, 141, 1771–1772, 1793
functional imaging of, 62–63
gender differences in, 91–94, 841–843, 842t
genetic contributions to, 96–97
good v. bad, 16
historical perspectives on
anatomically specific treatment, 8–9
cognitive treatment, 6–8
mechanistic views, 2–6
pain as specific sense (19th century), 3–5
pain treatment, 6–9
pharmacologic treatment, 8
philosophy or worldview, 1–2
specialty of pain medicine, 9
Loeser’s general model of, 85
origin of word, 6
parameters of, 103
physical pathology of, 11, 12f
prevalence of, 172, 1722
psychological aspects of, 76–89
psychophysiology of, 410–424
somatic v. visceral, 103–106, 106t, 1062, 1064–1065
subjectivity of, 11
suffering perspective of, 103
symptom perspective of, 103
taxonomies of, 15–22
terminology of, 11–15
time dimension of, 11, 12f, 16
unrelieved, as public health problem, 172
Pain (journal), 9
Pain, Enjoyment of Life, and General Activity (PEG) scale, 129, 227, 232,
289, 930, 1313
Pain appraisal, 77–78, 84–85
Pain Assessment Checklist for Seniors with Limited Ability to

5756
 Communicate (PACSLAC), 289
Pain Assessment in Advanced Dementia, 1772
Pain asymbolia, 108
Pain behavior, 14, 82–83
in anxiety and depression, 1416
assessment of, 313–314
culture and, 141–143
in ICU patients, 1783–1784
in Loeser’s model of pain, 85
observing and quantifying, 321–322
variables underlying, classes of, 313–314
Pain Behavior Checklists, 322
Pain Behavioral Assessment Tool (PBAT), 1784
Pain Beliefs and Perceptions Inventory (PBPI), 1305
Pain Catastrophizing Scale (PCS), 227, 230, 296, 323, 914, 1305, 1405
Pain centers and clinics, 14
emergencies and complications in, 1758–1769
anaphylaxis, 1764–1765
catastrophic neural injuries, 1765–1767
infectious, 1760–1761
intrathecal drug delivery, 1764
unintended destinations of local anesthetics, 1763
vasovagal reactions, 1763–1764
establishment of, 1794
multidisciplinary (interdisciplinary), 14, 324, 1494
Pain Coping Questionnaire, 915
Pain diagram, 228–229, 228f, 229f, 240
Pain Disability Index (PDI), 323, 664, 665t, 1304
Pain disorder, 446
Pain drawing, 285
Pain evaluation. See also Measurement of pain; specific conditions and
pain types
affective component in, 225
in arm and neck, 1159–1168
autonomic activation in, 225

5757
 cancer pain, 621–675
in children, 790–792
chronic (persistent) pain, 225–242
current and past treatments in, 232
disability evaluation in, 302–312
follow-up questionnaire in, 241
follow-up visits in, 236
function assessment in, 227, 232, 323
general guidelines for, 226–227
goals in, 232–233, 240–241
habits in, 231, 240
initial visit questionnaire in, 236–240
medical and surgical history in, 229–231, 239
medication history in, 232, 238–239
multidimensional questionnaire in, 227–228
pain history in, 228–229, 317
physical examination in, 233–236, 317
vocational history and disability in, 231
cognitive component in, 225
in cognitively impaired persons, 1734, 1734t, 1772
conceptual model for, 313–314
conundrums in, 313
in emergency department, 1771–1772
at end of life, 1733–1735
five A’s in, 236
in intensive care unit, 1783–1784, 1784t
multidimensions of pain in, 225–226, 226f
multidisciplinary (See Multidisciplinary assessment)
in primary care visits, 1726–1727
sensory component in, 225
time allotted for, 227
Pain exposure physical therapy (PEPT), 351, 1529
Pain history, 228–229, 317, 1159–1161
Pain in Sickle Cell Epidemiologic Study, 963
“Pain inhibits pain,” 63

5758
Pain interference
definition of, 286
measurement of, 227, 286–288, 290, 323, 1304–1305
in spine surgery candidates, 1304–1305
Pain location, 316–317, 316f
Pain management. See also specific drugs and treatments
clinical trials in, 123–135
cognitive-behavioral perspective on, 84
culture and, 141–143
efficacy v. effectiveness in, 130
emergency department, 1770–1781
ethical issues in, 151–158
barriers to pain relief, 153–156, 676
core values of health care, 151–152
curative v. palliative paradigms, 152, 152t
duty to relieve pain and suffering, 151, 152
opioid contracts, 156–157
pain relief as human right, 158
paradigm shift (new ethic) in, 151, 156–157
undertreatment, 151, 152–156
ethnic differences in, 95
gender differences in, 93–94
harms assessment in, 130–131
intensive care unit, 1782–1792
laws and policies affecting, 172–192
additional U.S., considering, 185–186
balance principle in, 174, 181, 184, 187–188, 207, 207t, 1001
barriers to safe and effective opioid use, 172–173, 215–221, 216t
diversion considerations in, 186–187
international access to opioids, 205–224
international treaties, 173–175, 206–208
policies governing opioid use, 173
UN recommendations on, 219–220
unrelieved pain as public health problem, 172
U.S. federal law on, 175–180

5759
 U.S. state laws, 180–185
litigation over, 193–204
administrative proceedings, 193–195
civil, 193, 195–198
constitutional cases, 201–202
criminal, 198–201
fear of, as professional barrier to pain relief, 154, 216, 676, 1725–
1726
federal prosecution, 199–201
lessons from, 203
naturalistic approaches in, 1434–1435
Pain Management Examination Committee, 1752
Pain Management Inventory (PMI), 1302, 1305
Pain matrix, 268, 268f, 1698. See also Neuromatrix
Pain medicine
ACGME-accredited programs in, 1752, 1752f
board certification in, 1751–1752, 1752f, 1753f, 1793
contributions from traditional specialties, 1754, 1754t
evidence-based, 1757–1758
evolution as subspecialty, 1751–1753
forensic, 193
4 A’s of, 1008
future of, 1793–1794
growth of, 1752, 1752f
history of, 9, 1751–1753
interventional, 711–731, 711t, 1756–1758, 1757t, 1794
IOM report on, 1793
as new discipline, 137
primary care providers and, 1722–1723, 1726
as primary medical specialty, 1753–1754
range of practitioners in, 1753
training in Europe, 1755
training specialists in, 1751–1757
universal precautions in, 617–618, 1007–1008, 1007t
Pain Medicine (Carr), 173

5760
Pain plasticity, 71–72
in chronic pain, 72, 72f
functional imaging of, 72, 72f
in hypnosis, 1424
in phantom pain, 72, 364
Pain points, 4–5, 5f
Pain & Policy Studies Group/WHO Collaborating Center for Policy and
Communications in Cancer Care (PPSG/WHOCC), 208, 208t, 215,
219–221
Pain processing
models of, 38
spinal, 38–51 (See also Spinal nociceptive processing)
Pain proneness, 437
Pain Quality Assessment Scale (PQAS), 279, 281–285, 282f–284f
Pain Quality Assessment Scale-Revised (PQAS-R), 279, 281–285, 286,
290
Pain Rating Index (PRI), 277–278, 940
Pain ratings, 16, 276, 276f. See also specific rating tools
Pain rehabilitation. See also Rehabilitation
definition of, 1491
history of, 1490
Pain relief. See also specific agents, procedures, and topics
definition of, 14
total, 15
Pain Response Inventory, 915
Pain Self-Efficacy Questionnaire (PSEQ), 1305
Pain sensitivity, 14, 1301
Pain Stages of Change Questionnaire, 1471
Pain threshold, 14
ethnicity/race and, 95
gender differences in, 92, 841–842
in noncardiac chest pain, 1037, 1037f, 1039–1040, 1039f, 1040f
Pain tolerance, 14
ethnicity/race and, 95, 139
gender differences in, 92, 841–842

5761
Pain treatment centers, 1494
painDETECT, 278, 279, 286, 290, 396, 397
Painful bladder syndrome, 1088–1089
Painful neuropathies. See Neuropathy(ies), painful
Painful trigeminal neuropathy (PTN), 1108, 1117–1118, 1128–1129, 1129t
classical trigeminal neuralgia v., 1108, 1112, 1117, 1128, 1691
multiple sclerosis and, 1117
neoplasm and, 1117
pathophysiology of, 1691–1692
posttraumatic (anesthesia dolorosa), 1123
surgical management of, 1691–1697
Painful xiphoid syndrome, 1190
Pain-prone personality, 319
PainTracker, 1313
Paleospinothalamic tract, 43, 108f
Palifermin, for oral mucositis prevention, 737, 738, 796
Palliative care, 205, 1732, 1734t
in cancer, 763–765, 764f
cancer and, 205, 618
for children with cancer, 802–803
curative paradigm v., 152, 152t
definitions of, 160, 802
doctor’s role and decision in, 160
HIV/AIDS and, 205
integration of, 1732, 1733f
models of, 1732, 1733f
pain syndromes in, 1732–1733, 1734t
transition from curative care to, 160–163
WHA resolution on, 219–220
Palliative chemotherapy, 763–765, 778–782. See also Chemotherapy
Palliative model, of cancer pain, 615, 616f
Palliative radiation therapy, 765–778. See also Radiation therapy
Palliative sedation, 168–169, 1739–1740, 1739t
Palmer, D. D., 1497, 1552
Palmitoylethanolamide, for central pain, 401t

5762
Palonosetron, for nausea/vomiting in cancer therapy, 684
Palpation, 233, 234, 1483
flat technique, 513–514, 514f
low back, 1251, 1264
neck (cervical spine), 1163–1164
pincer technique, 513–514, 514f
trigger point, 506, 506f, 513–515, 514f
Pamidronate, for bone pain in cancer, 746
PAMORAs. See Peripherally acting μ-opioid receptor antagonists
Pancoast syndrome, 754, 1201t
Pancoast’s tumor, magnetic resonance neurography of, 265f
Pancreas
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Pancreatic cancer, 638–639
epidemiology of, 622f, 638
fatigue in, 631–632
pain in, 638–639
abdominal, 639
back, 639
neural invasion and, 638–639
syndromes of, 639, 639t
tumor type and stage of disease in, 638
visceral, 628, 754
palliative radiation therapy for, 766
Pancreatitis
back pain in, 1246–1247
chest pain in, 1201t
chronic, pain in, 1066
in HIV/AIDS, 986
Panic attack, 441, 441t
Panic disorder, 80, 440, 441–442, 1041
Panniculitis, 554
Para-aminophenol derivative. See Acetaminophen
Parabrachial nucleus

5763
 in descending modulation of pain, 55–57, 55t
in pain–ANS interaction, 114–118
Paracervical block, for childbirth pain, 950
Paracetamol. See Acetaminophen
Paramedian zone, of brainstem, 63
Paraneoplastic pemphigus, 557, 754
Paraneoplastic peripheral neuropathy, 656–657
Paraneoplastic sensory neuronopathy, 335
Paraneoplastic syndromes, 626, 634–635, 656–657
Paraneoplastic vasculitis, 634, 657
Paraproteinemia, neuropathy with, 333
Parasellar syndrome, 653
Parasympathetic nervous system, 110, 111
cranial, 111, 112f
emotion and, 412
nerve supply from, 111t
sacral, 111, 112f, 113f
Parathyroid hormone-related peptide (PTHrP), in bone metastases and
pain, 745
Paratonia, 234
Paraventricular nucleus (PVN)
in emotion and noxious signaling, 414f, 415, 416, 416f
in stress, 419
Paravertebral compression, 1197t
Paravertebral ganglia, 112–113
Paravertebral nerve blocks (PVBs), 866–868
for acute pain, 837, 866–868
for childbirth pain, 940
clinical effects of, 868
contraindications to, 868
for herpes zoster, 378–379, 390
indications for, 866
landmarks for, 866, 867f
local anesthetic dosing in, 888t
parasagittal approach in, 868, 868f

5764
 for sensory mononeuropathies, 559
techniques for, 866–868
transverse approach in, 866, 867f
ultrasound guidance for, 866–868, 867f, 868f
Paré, Ambroise, 8, 363, 1751
Parecoxib, 1318, 1323
Parent(s), assessment measures for, 289, 790, 792, 915
Parent-controlled analgesia, 816
Parenteral morphine equivalents (PME), 829
Parenteral opioids, 1342, 1736
for acute pain, 828–829
for cancer pain, 698–699
systemic analgesia for, 946
Parenteral route, for end-of-life drug delivery, 1736
Parents’ Postoperative Pain Measure (PPM), 289, 790
Paresthesia, 14, 397, 1175
Parietal lobe, 62f
Paris, S. B., 1497, 1497t
Parkinson’s disease, 399
Parotid gland
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Paroxetine
for depression, 439
for fibromyalgia, 535, 537t
for neuropathic pain, 1360t, 1361t, 1362
for noncardiac chest pain, 1053
for tension-type headache, 1133
Paroxysmal extreme pain disorder (PEPD), 332–333
Paroxysmal hemicrania, 1026, 1026t, 1027, 1113, 1135
Paroxysmal sensations, 285
Parsons, Talcott, 445
Partial opioid agonists, 1335t, 1336
Partial-thickness burns, 897, 898f
Participation, as coping style, 904, 904f

5765
Particulate steroids
embolism of, 1765
neural injuries from injection, 1765–1767, 1767f
Parvocellular secretory cells, 64
PASS-20. See Patient Anxiety Symptoms Scale
Patellofemoral arthritis, 488–489
Patellofemoral joint pain, 1487
Pathologic fracture, 651f
in cancer, 649–650, 770–772, 771f
Patient(s)
difficult, 476–478
expectations of, 76, 84, 476, 1406–1407, 1726
individual differences in pain, 90–102
as medical consumers, 137
pain narrative of, 143
Patient Anxiety Symptoms Scale (PASS-20), 296
Patient barriers, to pain relief, 155
“Patient dumping,” 154
Patient encounters
clinical scenarios of, 480–482
communication framework for, 479–480, 479t
difficult, 476–483
4 E’s of, 480, 480t
strategies for, 478–479
Patient global impression of change (PGIC), 14
Patient Health Questionnaire (PHQ), 298
in cancer, 630–631, 631t
in chronic pain, 227, 228, 322
in spinal cord injury, 581
in substance use disorder, 467
Patient Self-Determination Act, 163
Patient triage, 1008, 1008t
Patient-controlled analgesia (PCA)
for acute pain
epidural, 835, 836t

5766
 intravenous, 832–833, 832t
adverse events in, 832–833
for burn pain, 902
for cancer pain, 698–699, 701
for cancer pain in children, 795–796, 798
for childbirth pain, 946, 949
for children, 816, 816t
in emergency department, 1776
gender differences in, 93
home-based, 701
intrathecal, 714
money/power and access to, 145
for oral mucositis, 738
programming devices for, 832, 832t
for sickle cell disease pain, 974–975
Patient-controlled epidural analgesia (PCEA), 851, 853
Patient-focused care, 479
Patient-Reported Outcomes (PROs), 227
Patient-Reported Outcomes Measurement Information System (PROMIS),
227, 467–468, 791, 792, 914, 1313. See also specific PROMIS
measures
Pauciarthritis, 485, 486t
Pavlov, Ivan, 425, 425f, 1421
PBAT. See Pain Behavioral Assessment Tool
PBCL. See Procedure Behavior Checklist
PBN. See Parabrachial nucleus
PBPI. See Pain Beliefs and Perceptions Inventory
PCA. See Patient-controlled analgesia
PCC. See Posterior cingulate cortex
PCEA. See Patient-controlled epidural analgesia
PC-PTSD. See Primary Care-PTSD
PCS. See Pain Catastrophizing Scale
PDAPS. See Prescription Drug Abuse Policy System
PDI. See Pain Disability Index
PDMP. See Prescription monitoring program

5767
PDPH. See Postdural puncture headache
PDUQ. See Prescription Drug Use Questionnaire
“Peak” effects, 274
Pectoral blocks
PECS I and PECS II, 885–886
clinical effects of, 886
indications for, 885
injection techniques for, 885, 885f, 886f
ultrasound guidance for, 886, 886f
for postsurgical breast pain, 1191
Pectoral girdle
anatomy of, 1150–1158
common disorders of, 1150
movements of, 1156, 1156t, 1157f, 1159f
Pediatric Oncology Group of Ontario, 796
Pediatric Pain Screening Tool (PPST), 914
Pediatric Quality of Life Inventory, 914
Pediatric Regional Anesthesia Network (PRAN), 818, 819
Pedicle screws, and failed back surgery, 1289
PedIMMPACT, 916
PEG. See Pain, Enjoyment of Life, and General Activity (PEG) scale
Pegfilgrastim, pain from, 651, 795
Pegloticase, for gout, 500
Pellagra neuropathy, 332
Pellegrino, Edmund, 141
Pelvic abscess, 1208
Pelvic compression test, 1210, 1210f
Pelvic floor abnormalities, 1089
Pelvic infection, assisted conception procedures and, 1083
Pelvic inflammatory disease (PID), 1080, 1088
Pelvic metastases, 645t
Pelvic pain
cancer-related, 755
palliative radiation therapy for, 766–767
chronic, 1098t

5768
 definitions of, 1098, 1098t
peripheral nerve stimulation for, 1105, 1564–1565
peripheral neurectomy for, 1672
superior hypogastric plexus neurolysis for, 719–720
Pelvic pain, female, 1079–1095
acute, 1079–1084
adnexal pathology and, 1080
assessment of, 1079–1080, 1080f
assisted conception complications and, 1082–1083
ectopic pregnancy and, 1079, 1079t
exacerbation of chronic pain, 1081
fibroid degeneration and, 1082
gynecologic factors in, 1080–1081
hematometra/hematocolpos and, 1081
ligamentous stretch and, 1082
miscarriage and, 1081–1082
nongynecologic causes of, 1079, 1079t
ovarian cyst accident and, 1080, 1082
pelvic inflammatory disease and, 1080
pregnancy-specific complications and, 1081–1082
uterine retroversion and, 1082, 1082f
chronic, 1079, 1084–1090
acute exacerbation of, 1081
adenomyosis and, 1087
adhesions and, 1087–1088
assessment of, 1085–1086, 1085t
diagnostic laparoscopy in, 1085
empirical treatment for, 1086
endometriosis and, 1086–1087, 1086t
gastrointestinal factors in, 1088
gynecologic factors in, 1086–1088
history of, 1085
hormonal treatments for, 1085, 1086t
investigations in, 1085
musculoskeletal factors in, 1089

5769
 neurologic factors in, 1089–1090
pelvic inflammatory disease and, 1088
personality and, 1085
physical examination of, 1085
physical or sexual abuse and, 1084
psychological factors in, 1084–1085
social factors in, 1084
as symptom, 1084
therapeutic trial in, 1085
urologic factors in, 1088–1089
venous congestion and, 1088
visceral hypersensitivity in, 1086
dysmenorrhea and, 1083–1084
dyspareunia and, 1090–1091, 1091t
epidemiology of, 1079
hypnosis for, 1426–1427
mittelschmerz and, 1084
vaginismus and, 1090–1091, 1091f
vulval pain syndromes and, 1091–1092
Pelvic pain, male, 1096–1107
centrally acting analgesics for, 1105
chronic, taxonomy and phenotyping of, 1096–1100
classical pathologies of, 1096
epidemiology of, 1099
functional problems in, 1103, 1103t
incidence/prevalence of, 1099
mechanisms of, 1099–1103
central, 1100
peripheral, 1100
muscles and, 1100–1102, 1101f
negative sexual encounters and, 1099
neuromodulation for, 1105
pelvic nerves and, 1102–1103
pelvic pain syndromes v. nonpelvic pain syndromes in, 1096–1098,
1097t

5770
 precipitating factors in, 1099
psychological consequences of, 1103
psychological interventions for, 1104
sexual counseling for, 1104
surgery for, 1105
treatment of, 1103–1105
trigger point therapy for, 1104
visceral v. nonvisceral somatic, 1099, 1100t
Pelvic pain syndromes, 1096–1098, 1097t
confusable, 1096
definition of, 1098, 1098t
male-specific, 1098, 1098t
muscle, 1101–1102
peripheral nerve, 1102–1103
spinal and abdominal muscle, 1102
subclassification by organ, 1098
well-defined, 1096
Pelvic plexuses, 111, 113f
Pelvic venous congestion, 1088
Pelvic viscera, sympathetic and nociceptive nerve supply to, 117t
Pembrolizumab, 779
PEMF. See Pulsed electromagnetic field therapy
Pemphigus vulgaris, 557
Penile pain syndrome, 1098t, 1099
Pennebaker, James, 143
PENNSAID, 1318, 1319t
Pentagastrin stimulation test, 1046
Pentazocine, 1334t, 1346
avoidance in cancer pain, 696
intravenous patient-controlled, 832t
metabolites of, 1348t
respiratory depression with, 1338
Pentobarbital
in emergency department, 1778
for palliative sedation, 1739t

5771
Pentosan polysulfate, 1070
Pentoxifylline, 548, 550, 969
PEPD. See Paroxysmal extreme pain disorder
Peppermint oil, 923, 1072
PEPT. See Pain exposure physical therapy
Peptic ulcer disease, 1201t
Perceived control, 78–79, 142
Perception, altered, 229
Perceptions, culture and, 141–143
Perceptual distortions, 234
Perceptual dysfunction, 234
Percutaneous balloon compression, for trigeminal neuralgia, 1695
Percutaneous cordotomy, 1657, 1700
Percutaneous gangliolysis, for trigeminal neuralgia, 1115–1116
Percutaneous intradiscal radiofrequency thermocoagulation (PIRFT),
1647–1648
Percutaneous intrathecal catheter, 712
Percutaneous rhizotomy, for trigeminal neuralgia, 1691, 1694–1695, 1695f
Perforated ulcer, 1201t
Performance status, in cancer pain, 664, 665t
Periaqueductal gray (PAG), 63–64, 108
in acute pain, 827
in ascending modulation of pain, 109
biologic significance of modulation, 64
in construction and modulation of pain, 417
deep brain stimulation of, 64, 1587–1589
in descending modulation of pain, 54–56, 55t, 56f, 63–64, 109
in emotion-related behaviors, 63
in fight or flight, 64
in opioid-induced hyperalgesia, 59
in pain–ANS interaction, 114
regional distribution for pain in, 64
in somatic v. visceral pain, 106
in stimulus-induced analgesia, 64
in stress, 419

5772
 in stress-induced analgesia and hyperalgesia, 59
Periarticular anastomosis, 485
Pericarditis, acute, 1193t
Pericoronitis, 1130, 1131t
Perineal infiltration, for childbirth pain, 951
Perineal pain, 1088
cancer-related, 640–641, 653
corticosteroid-induced, 756
malignant, 755
peripheral neurectomy for, 1670
Perineural clonidine, 854
Perineural dexamethasone, 854
Perineural dexmedetomidine, 854
Perineural opioids, 853–854
Periodicity
of cluster headache, 1025
of low back pain, 1250, 1263
Periodontal disease, 1130–1131, 1131f
Periodontitis, 1130
Perioperative hypnosis, 1427–1428
Peripheral analgesia, adjuvants for, 853–854
Peripheral field stimulation (PFS), 1558
for axial back pain, 1564
complications of, 1566
future directions in, 1567
indications for, 1563t
mechanism of, 1559
for pelvic and groin pain, 1564–1565
technology for, 1559–1560
Peripheral nerve(s), 103. See also Neurolytic blockade
cutaneous fields of, 103, 105f
magnetic neurography of, 251, 262–267
tumor infiltration of, 637
Peripheral nerve blocks, 856–857. See also Nerve blocks
Peripheral nerve catheters, 856–857

5773
Peripheral nerve entrapment syndromes, 267–268. See also Nerve
entrapment; specific nerves
Peripheral nerve stimulation (PNS), 1558–1569
for axial back pain, 1564
complications of, 1566
future directions in, 1567
gate-control theory and, 1558–1559
for headache and facial pain, 1565–1566
implantation techniques for, 1560–1563, 1560f–1561f
open surgical, 1560
percutaneous, with fluoroscopic guidance, 1560–1561, 1562f
percutaneous, with ultrasound guidance, 1561–1563, 1561f, 1562f
indications and outcomes, 1563–1566, 1563t
pathophysiology and mechanisms of analgesia in, 1558–1559, 1558f
patient selection and preoperative workup for, 1563
for pelvic and groin pain, 1105, 1564–1565
for phantom pain, 367
technologies for, 1559–1560, 1560f
Peripheral nervous system
autonomic, 110–111, 110f, 111f (See also Autonomic nervous system)
cutaneous fields in, 103, 105f
dermatomes in, 103, 104f
emotion and, 412–414
functional neuroanatomy of, 103–106
organization of, 103–106
somatic v. visceral pain in, 103–106, 106t
structures of pain sensation in, 106
surgery, as pain treatment, 1668–1690 (See also specific surgeries)
Peripheral neurectomy, 1668–1672
basic considerations in, 1668–1669
clinical considerations in, 1669–1670
for neuropathic pain, 1670–1671
for nociceptive pain, 1671–1672
operative technique in, 1670
preoperative evaluation for, 1669–1670

5774
 for trigeminal neuralgia, 1116–1117
Peripheral neurogenic pain, 14
Peripheral neuropathy. See Neuropathy(ies)
Peripheral pain mechanisms, 24–37
action potential generation in, 26, 30–31
action potential propagation in, 26, 31
clinical implications of nociceptor function, 33–34
functional characterization of nociceptors, 24
generator potential in, 26, 30
identification of putative nociceptors, 25–26
neurotransmitter release in, 29f, 31–32
nociceptor characteristics, 26–32
signal transduction in, 26–30, 27f–29f
Peripheral sensitization, 58
in abdominal pain, 1066
in hyperalgesia, 58
in myofascial pain (trigger points), 508–509
in noncardiac chest pain, 1039
in pelvic pain
female, 1088, 1089
male, 1100
in postherpetic neuralgia, 382–383
prevention of, 827–828
Peripheral vascular disease, spinal cord stimulation for, 1575
Peripherally acting μ-opioid receptor antagonists (PAMORAs), 683
Periscapular pain, biomechanical considerations in, 1485–1486
Peritoneal carcinomatosis, 652–653, 755
Peritoneal dialysis, and opioid therapy, 687–688, 688t
Permanent disability, 311
Peroneal nerve. See Fibular (peroneal) nerve, anatomy of
Peroneal nerve entrapment, 1678
Peroral endoscopic myotomy (POEM), 1052
Persistent idiopathic facial pain, 1108, 1108t, 1113
Persistent pain. See Chronic pain
Personal choice and control, in behavioral change, 1475

5775
Personality, 444–445
and chronic pain, 318–319
and doctor–patient relationship, 476–477
and female pelvic pain, 1085
and pain, 76–77, 81
and pain treatment outcome, 445
and spine surgery, 1303t, 1304
Personality disorders, 444–445
Personalized medicine, 779
Perspective, patient, 479–480, 479t
Pes cavus, 1219, 1219f
Pes planus, 1219, 1219f
PET. See Positron emission tomography
Pethidine. See Meperidine
PEVK segment, 506
Pfannenstiel incision, neuropathy secondary to, 1090
PFC. See Prefrontal cortex
Pfizer, 199
PFS. See Peripheral field stimulation
PGIC. See Patient global impression of change
pH
and bone pain in cancer, 745
and cancer pain, 627
esophageal, monitoring of, 1037, 1038, 1043
and local anesthetics, 1386–1387
and muscle pain, 511
Phalen sign, 249, 1174
Phantom breast pain, 658, 1191
Phantom limb pain, 8, 363–371, 571
behavioral medicine interventions for, 368
cancer-related, 658
in children, 795, 911
definition of, 363
desensitization for, 368, 1529
electrodiagnostic studies of, 364

5776
 epidemiology of, 363
exteroceptive component of, 363
hypnosis for, 1428
interventional therapy for, 366–367
modulation of, 363
neuromatrix in, 364
pathophysiology of, 363–364
plasticity in, 72, 364
prevention of, 364–365
psychological factors in, 364
surgical interventions for, 367–368
telescoping in, 363
topographical remapping in, 364
treatment of, 365–368
Pharmaceutical companies
aggressive marketing by, 1312, 1517
drug approval process for, 175–176, 1313
mergers of, 144–145
studies conducted by, 1313
Pharmacist, clinical pain, 1712
Pharmacodynamic tolerance, 1339
Pharmacodynamics, 1311, 1314
of local anesthetic, 1383, 1383f
of opioid analgesics, 1336
Pharmacoeconomic analyses, 1313, 1313t
Pharmacokinetic tolerance, 1339
Pharmacokinetics, 1311, 1314. See also specific drugs
end-of-life organ dysfunction and, 1736
of intrathecal drugs, 1623, 1623f
of local anesthetics, 1383–1384
of NSAIDs, 1317–1318
Pharmacologic tolerance, 1339
Pharmacology
clinical, 1311
definition of, 1311

5777
Pharmacotherapy. See also specific drugs and conditions
definition of, 1311
for pain, 1311–1314
alternatives to, 1311, 1311t
approved drugs and drugs for nonapproved uses, 1313
as component of multimodal treatment, 1311–1312
efficacy of, 1313
historical perspective on, 8
outcome analyses for, 1313, 1313t
rational, 1314
risk-to-benefit considerations in, 1312
symptom control v. side effects in, 1312
synergism and potentiation in, 1312–1313
treating cause of pain v., 1312
underuse and overuse of, 1311
Pharmacovigilance, 156
Phenic nerve palsy, 859
Phenobarbital, for palliative sedation, 1739t
Phenol injection
for neurolytic blockade, 711t, 716–717, 716f, 1653, 1654
for trigeminal neuralgia, 1115
Phenomenal awareness, 411
Phenoxybenzamine
for complex regional pain syndrome, 353
for sympathetically maintained pain, 1684
Phentolamine
for complex regional pain syndrome, 353, 354
systemic infusions of, 1683
Phenylbutazone, 1315
Phenytoin
for Fabry’s disease, 560
for painful neuropathies, 337
for trigeminal neuralgia, 1114–1115
Philosophy, pain as part of, 1–2
Phlebitis

5778
 chemotherapy-related, 756
superficial, 570
PHN. See Postherpetic neuralgia
Phosphorus-32, for bone pain in cancer, 747, 777–778, 777t
Phosphorylation of extra cellular signal-related kinase (pERK), 38–39, 41
Photobiomodulation, in oral mucositis, 737, 740
PHQ. See Patient Health Questionnaire
Physical abuse, and pelvic pain, 1084
Physical capacity. See also Functional capacity evaluations
assessment of, 323–324
and job duty, 1501, 1503t
measuring, 1501
Physical dependence, 14, 179, 454–457, 840, 1001–1002. See also
Substance use disorder
addiction v., 1001, 1002
definition of, 1002t, 1340, 1772
opioid, 456–457, 1340
Physical examination, 233–236, 317
in abdominal pain, 1064
bedside method for sensory testing in, 235–236
biomechanics in, 1483–1484
in cancer pain, 610–613, 665, 667, 790
in chronic pediatric pain, 915
in female pelvic pain, 1085
general exam in, 233
in joint pain (arthritis), 486
in low back pain, 1251–1252
in neck and arm pain, 1162–1167
neurologic exam in, 233–235
in neuropathy, 330
in substance use disorder, 1509
Physical modalities, for neurolytic blockade, 1653
Physical pathology, of pain, 11, 12f
Physical therapist, 1712
Physical therapy

5779
 for ankylosing spondylitis, 494–495, 1188
for avascular necrosis, 970
biomechanics in, 1480–1489
for central pain, 403
for children with chronic pain, 916, 921
for chronic pain, group, behavioral approaches v., 1456
for complex regional pain syndrome, 351
for costochondritis, 1189
for costovertebral arthritis, 1188
for elderly patients, 934
evaluation for, 1537, 1538f
for failed back surgery, 1294
for femoral nerve entrapment, 1213
for low back pain, 1254, 1271, 1456, 1537–1545
for myofascial pain (trigger points), 515
pain management in
biophysical agents for, 1522–1536
cryotherapy for, 1523–1524
electroanalgesia for, 1526–1529
emerging interventions for, 1530–1532
light therapy for, 1524–1525
somatosensory desensitization for, 1529–1530
thermotherapy for, 1522–1523
ultrasound therapy for, 1525–1526
for rehabilitation, 1497
for sciatic nerve entrapment, 1217
for spinal cord injury pain, 594
in spine clinics, 1718–1719
for thoracic facet syndrome, 1188
for thoracic outlet syndrome, 579, 1176
Physician duty, 151, 152
Physician Orders for Life-Sustaining Treatment (POLST), 165
Physician-assisted death, 168–170
aggressive symptom management in, 168–169
Canadian Supreme Court decision on, 202

5780
 cessation of eating and drinking in, 169
clinical care in, 169–170
ethical considerations along clinical spectrum in, 168–169
legalization of, momentum in, 202
levels of response in, 169–170
prescription for lethal dose in, 169
sedation in, 169
social policy on, 169
steps for physicians in, 169
terminology for, 168
U.S. Supreme Court decision on, 201–202
Physician/medical director, 1711
Physician–patient relationship
in abdominal pain, 1069
adversarial, 1725
barriers to pain relief in, 153–155
in death and dying (See also Physician-assisted death)
decision-making in, 160–162
honesty v. hope in, 162
joint participation in, 160
patient attitudes and values in, 161
physician attitudes and values in, 161–162
prognosis and clinical judgment in, 161
response to demands for nonbeneficial treatment, 166–168
in pain management
clinical scenarios of, 480–482
communication in, 479–480, 479t, 480t
comorbid conditions and, 477–478
difficult, 476–483
difficult “normal” patients in, 477
difficult patients in, 476–478
health care system factors in, 476, 478
mutuality and, 1745
opioid therapy and, 477
patient interaction strategies in, 478–479

5781
 patient psychiatric and personality issues in, 476–477
patient-focused care in, 479
physician factors in, 476, 478
substance use disorders and, 478
trust and, 1744–1745
Physicians’ assistants, 1711
Physostigmine, for baclofen withdrawal, 1764
Pia, of spinal cord, 39
PID. See Pelvic inflammatory disease
Pieces of Hurt/Poker Chip Tool, 790
Pilates, 1541, 1543
Pill counts, 1004, 1012
Pill loads
avoiding excessive, 1013–1014
limits to modify behavior, 1014
PILT. See Pulsed infrared light therapy
Pimozide, for trigeminal neuralgia, 1114
Pincer palpation technique, 513–514, 514f
Pineal gland, 62f
Piriformis muscle, sciatic nerve and, 1215, 1216f
Piriformis syndrome, 267, 1101, 1216–1217, 1289–1290
Piroxicam, 685, 1316t, 1319t, 1322
Pittsburgh Sleep Quality Index (PSQI), 633
Pizotifen, 923, 1023t
Placebo, 14, 124–125, 1069
Placebo effects, 14, 123, 144
nerve blocks v., 1600, 1601–1602, 1605, 1607–1608
Plantar fasciitis, 1219–1220
Plasma exchange
for ANCA vasculitis, 547
for antiphospholipid syndrome, 548
Plasticity
neural, 14
pain, 71–72
in chronic pain, 72, 72f

5782
 functional imaging of, 72, 72f
in phantom pain, 72, 364
Platelet-derived growth factor (PDGF), in cancer pain, 627, 647
Platelet-rich plasma (PRP), intradiscal, 1650
Platelets, NSAIDs and, 1327
Pleasurable activities, 1408
Plensa, Jaume, 146, 146f
Pleural disorders, 1194t–1195t
Pleuritic pain, 987, 1194t–1195t
Pleuritis, 1195t, 1196t
Pleurodynia, epidemic, 1190, 1195t
Plyometric exercise, 1498
PME. See Parenteral morphine equivalents
PMI. See Pain Management Inventory
PMP. See Prescription monitoring program
Pneumocystis carinii, 985, 987
Pneumonia, 1194t
Pneumothorax, 1194t
malpractice claims over, 1758, 1759f
in PECS/serratus anterior plane block, 886
in supraclavicular block, 859
Podagra, 499
POEMS syndrome, 333, 657
Poetry therapy, 800–801
Policy. See Law and policies, affecting pain management
The Politics of Life Itself (Rose), 137
POLST. See Physician Orders for Life-Sustaining Treatment
Polyanalgesic Consensus Conference, 1375, 1624, 1625t, 1632
Polyarteritis nodosa (PAN), 334, 544t, 546–547
Polyarthritis, 485–486, 486t
Polyethylene glycol 3350, 798–799
Polymodal nociceptor, 24
Polymyalgia rheumatica (PMR), 501–502, 1251
Polymyositis, 989, 1199t
Polymyxin lozenges, 738

5783
Polyneuropathies, electrodiagnostic tests in, 249
Polypharmacy
in complex regional pain syndrome, 351
in neuropathy, 338
rational, 1312
POMC. See Pro-opiomelanocortin
POMS. See Profile of Mood States
Pons, 55t, 56f, 62f
Pope, Alexander, 2
Popliteal entrapment syndrome, 568–569, 568f
Popliteal fossa approach, 821, 878, 879, 880f
Population groups, 140
Portenoy, Russ, 1751
Positive sharp waves, 247, 247f
Positron emission tomography (PET), 62–63
in bone cancer, 745
in complex regional pain syndrome, 343, 344, 345
in esophageal sensory testing, 1050
in females v. males (differences in pain), 841
in fibromyalgia, 530
in headache, 1020, 1020f, 1021f
in hypnosis, 1423–1424
in insula, 67
in occipital nerve stimulation, 1565
in opioid therapy, 1336
in paroxysmal hemicrania, 1027
in prefrontal cortex, 68–70, 69f
in primary somatosensory cortex, 66
in secondary somatosensory cortex, 67
Postcardiac surgery pain, 1191
Postdural puncture headache (PDPH), 715, 948, 1635
Posterior cingulate cortex (PCC), 66f, 67
Posterior cord, of brachial plexus, 1147
Posterior interosseous nerve syndrome, 1676
Posterior longitudinal ligament, 1140t, 1141, 1142f

5784
Posterior spinocerebellar tract, 40f
Posterior sternoclavicular ligament, 1150
Posterior tibial nerve, 882
Posterior tibial tendon insufficiency, 1221
Posterior triangle nerves, damage to, 1102–1103
Postganglionic neurons, 110–111, 111f
parasympathetic, 111, 113f
sympathetic, 113–114, 113f
Postherpetic neuralgia (PHN), 335, 372–395
adjuvant analgesics for, 685
age and, 335
allodynia in, 330, 1186
antidepressants for, 384t, 386, 1118, 1186
antiepileptic drugs for, 383–386, 384t, 1118, 1186
in cancer patients, 636
cancer treatment and, 782
chest wall pain in, 1185–1186, 1197t
clinical picture of, 380–381, 1118, 1186
combination therapy for, 388
diagnosis and assessment of, 381, 1118
dorsal rhizotomy or ganglionectomy for, 1682
dorsal root ganglion stimulation for, 389, 1565
electroanalgesia for, 390
epidemiology of, 335, 381, 1118
etiology of, 1117
interventional therapies for, 388–389, 1186
laboratory testing in, 381
laser therapy for, 1524–1525
natural history of, 381
neuroaugmentive techniques for, 389
NMDA receptor antagonists for, 388
opioid analgesics for, 385t, 386–387, 1186
painful trigeminal neuropathy in, 1117–1118
pathophysiology of, 382–383, 382f
pharmacologic options for, 383–388, 384t–385t

5785
 prevention of, 390–391, 1118
psychological interventions for, 390
risk factors for, 381, 382t
surgical approaches in, 390
symptoms and signs of, 1118
topical therapies for, 385t, 387–388, 1186
treatment of, 383–390, 391, 1118, 1186
trigeminal, 1129
well-established, 380
Postlumbar puncture headache (PLPHA), 795
Postmarket promotional material, 175–176
Postmastectomy pain syndrome, 657, 1190–1191, 1200t
Postoperative delirium, in elderly, 839–840
Postoperative pain. See also Acute pain
in ambulatory surgical patients, 839
in burn injury, 898, 903
in cancer patients, 657–658
chest wall, 1190–1191, 1199t
chronic, 843
in elderly patients, 839–840
enhanced recovery programs for, 826, 837
gender differences in, 92
in head and neck cancer, 733–734
inpatient pain services for, 843
intravenous lidocaine for, 1387
measurement of, 289
monitoring and documentation of, 828, 828t
nerve blocks for, 1607
in pediatric cancer patients, 795
prevention of, 827–828
in substance-abusing patients, managing, 462t, 463–464
Postphlebitic syndrome, 570
Postsurgical inflammatory neuropathy, 887
Postsympathectomy neuralgia, 573
Postsynaptic dorsal column neurons, 45

5786
Postthoracotomy pain, 658, 1191, 1200t
Posttraumatic headache, 1031, 1135
Posttraumatic stress disorder (PTSD), 440, 442–444
assessment for, 229–230, 298–299
burn pain and, 899
in children, 914
in chronic pain, 1411
cognitive-behavioral therapy for, 1411
diagnosis of, 442
DSM criteria for, 443t
epidemiology of, 443–444
in failed back surgery, 1293, 1295
in fibromyalgia, 1415
fibromyalgia with, 531
pain association with, 435–436, 443–444
in spine surgery candidates, 1302
treatment of, 444
Posttraumatic syringomyelia (PTS), 585–586
Postural orthostatic tachycardia syndrome, 1030
Postvasectomy pain syndrome, 1098t
Potassium, in muscle physiology, 507
Potassium iodide, for erythema nodosum, 554
Potentiation, in pharmacotherapy, 1312–1313
Power, and pain, 144–146
Power & Illness (Krause), 144
PPIs. See Proton pump inhibitors
PPM. See Parents’ Postoperative Pain Measure
PPSG/WHOCC. See Pain & Policy Studies Group/WHO Collaborating
Center for Policy and Communications in Cancer Care
PPST. See Pediatric Pain Screening Tool
PQAS. See Pain Quality Assessment Scale
PQRST method, 790
Pragmatic trials, 131
Pramipexole, for fibromyalgia, 538
PRAN. See Pediatric Regional Anesthesia Network

5787
Prana, 1552, 1554
Prazosin, 444, 1684
Precordial catch syndrome, 1190
Predispositions, 76–77
Prednisone
for bullous pemphigoid, 558
for calcium pyrophosphate deposition disease, 497
for giant cell arteritis, 502
for gout, 500
for polyarteritis nodosa, 547
for polymyalgia rheumatica, 502
for psoriatic arthritis, 496
for rheumatoid arthritis, 493
Preemptive analgesia, 53
Prefrontal cortex (PFC), 65, 66f, 68–70
in addiction, 1002–1003, 1003f
in allodynia, 70
in depression–pain association, 436, 436f
in emotion and pain, 412, 417
functional imaging of pain in, 68–70, 69f
human v. nonhuman, 68
in motivation, 1470
subdivisions of, 68
Pregabalin
for abdominal pain, 1069
for acute pain, 830–831
for cancer pain, 689
for central pain, 400, 401t, 402, 402f
for chemotherapy-induced peripheral neuropathy, 686
for children, 917, 918
for chronic pelvic pain, female, 1086
for complex regional pain syndrome, 352
for elderly patients, 933
for failed back surgery, 1295
for fibromyalgia, 529–530, 537, 537t

5788
for herpes zoster, 378, 379t

5789
 for HIV pain, 994t, 996
for low back pain, 1271
for male pelvic pain, 1105
for neuropathic pain, 400, 402, 686t, 1362, 1364t
for painful neuropathies, 336–337
for phantom pain, 365, 795
for postherpetic neuralgia, 383–386, 384t, 1118
for postherpetic neuralgia prevention, 390
side effects of, 402
for spinal cord injury pain, 590, 591
for trigeminal neuralgia, 1114–1115
for vulvodynia, 1092
Preganglionic neurons, 110, 111f, 1148–1150, 1155f
parasympathetic, 111, 113f
sympathetic, 112–113, 113f
Pregnancy. See also Obstetric pain
analgesic drugs during, 952
complications of, pelvic pain in, 1081–1082
drug classification during, 951–952
ectopic, 1079, 1079t, 1081
heterotopic, 1081
ligamentous stretch in, 1082
local anesthetics in, 1387
loss of (miscarriage), 1081–1082, 1082t
lumbosacral plexopathy in, 1208, 1209f
nonobstetric drug therapy during, 951–952, 951t
opioid analgesics in, 1081, 1341
pain and pain response in, 140
physiologic changes of, 942–945
anesthetic implications of, 943t, 944
cardiovascular, 943–944, 943f, 943t, 944f
central nervous system, 943t, 944
pharmacokinetics, 943t, 945
respiratory, 943, 943t
transfer of drugs across placenta, 945

5790
 uterine retroversion in, 1082, 1082f
Pregnancy and Lactation Labeling Rule (PLLR), 951–952
Pregnancy testing, in pelvic pain, 1080
Premature ejaculation, pelvic pain and treatments causing, 1103, 1103t
Premature Ejaculation Diagnostic Tool, 1103
Premotor cortex, 108
Preschoolers, cancer pain in, 788
Prescription Drug Abuse Policy System (PDAPS), 231
Prescription Drug Abuse Prevention Plan, 187
Prescription drug monitoring program (PDMP). See Prescription
monitoring program
Prescription Drug Use Questionnaire (PDUQ), 465
Prescription drug use/misuse, 297–298. See also Substance abuse
Prescription duration, 179, 181–182, 181t, 182t
Prescription forms, multiple-copy, 174, 181
Prescription monitoring program (PMP), 181–182, 184, 231–232, 297–
298, 1012, 1518, 1747–1748
Prescription series, 179
Prescriptions, controlled substance, 177
Presenteeism, 76
Presumptive urine drug testing, 1015–1016, 1017
Pre-trigeminal neuralgia, 1112
Preventive analgesia, 827–828
Prevertebral ganglion, 111, 114
PRI. See Pain Rating Index
Priapism, in sickle cell disease, 968–969
Prilocaine, 1386t
Prilocaine-lidocaine cream (EMLA), 794, 903, 1386, 1389
Primary afferents, 106
in acute pain, 827
C-fiber, 41, 42f
neurotransmitters from, 45–48
spinal laminae, 39–42, 41f, 107, 108f
targets of axonal projections, 43–45
targets of input, 39–43

5791
Primary Care Evaluation of Mental Disorders (PRIME-MD), 467
Primary care pain management, 1722–1731
addressing barriers to care in, 1725–1726
adversarial physician–patient relationship in, 1725
assessment and evaluation in, 1726–1727
barriers to treating pain in, 1724–1726
challenges in, 1723–1724
collaboration with pain specialists in, 1726
comorbid conditions in, 1725
decision to treat or not to treat in, 1723–1724
five A’s of treatment success in, 1728, 1728t
goal setting and action plan in, 1727
goals for self-management in, 1729
lack of guidelines specific to, 1724
model of, 1726–1730
new focus in, 1726
pain medicine training in, 1723, 1726
patient expectations in, 1726
patient nonadherence in, 1724
pharmacologic, 1727–1728
referral to addiction specialist, 1728
regulatory scrutiny in, 1725–1726
specialty referrals in, 1724–1725
substance misuse screening in, 1727
time constraints in, 1724
Primary Care-PTSD (PC-PTSD), 299
Primary cortex, 65
Primary cough headache, 1028
Primary dysmenorrhea, 1083
Primary exertional headache, 1028, 1134
Primary fibromyalgia, 528
Primary generalized osteoarthritis, 487
Primary gout, 498
Primary headache, 1019–1020, 1133–1134
anatomy and physiology of, 1019–1020, 1020f

5792
 disabling, 1019
Primary osteoarthritis, 487
Primary process, 1422
Primary sex headache, 1028
Primary somatosensory cortex, 65, 66–67, 66f
in emotion and pain, 412
functional imaging of, 66–67, 66f
somatotopic organization of, 66, 66f
Primary stabbing headache, 1026, 1026t, 1027–1028
Primary thunderclap headache, 251, 1029
PRIME-MD. See Primary Care Evaluation of Mental Disorders
Probenecid, for gout, 500, 1224
Problem-solving skills training (PSST), 918, 1476
Procaine
molecular structure of, 1382, 1382f
for trigger point injections, 516
Procedural pain
in burn injury, 897–898, 902–903
pharmacologic options for, 903
preparatory information on, 904
in childhood cancer, 794–795
hypnosis for, 1427–1428
Procedural sedation and analgesia (PSA)
in emergency department, 1775, 1777–1778
for pediatric cancer patients, 794
Procedure Behavior Checklist (PBCL), 289
Procedure Behavior Scale–Revised, 289
Prochlorperazine
for nausea/vomiting in cancer therapy, 683–684, 684t
for opioid withdrawal, 1764
Proctalgia fugax, adjuvant analgesics for, 686–687
Proctitis
adjuvant analgesics for, 687
radiation, 756–757
Prodrome

5793
 in herpes zoster, 372
in migraine, 1133
in vascular occlusive crisis, 961–962, 961f, 962t
Professional barriers, to pain relief, 153–154, 215–216
in cancer, 623–625
deficiencies in physician education, 153–154, 216, 623–625, 1793
fear of scrutiny or liability, 154, 216, 676, 1725–1726
“patient dumping,” 154
primary care and, 1724–1726
Professional practice, course of, 178
Profile of Mood States (POMS), 322, 467, 631t
Progestogens, for endometriosis, 1086t
Prognosis, and end-of-life care, 161
Prognosis-based classification, 17
Prognostic blocks, 1599–1600, 1599t
Progress Report Card, on state pain policies, 182–185, 184t
Progressive multifocal leukoencephalopathy, 989
Progressive muscle relaxation, 1407
Progressive polyradiculopathy, in HIV/AIDS, 989
Progressive relaxation, in hypnosis, 1433
Proliferants, intradiscal, 1649
Prolonged exposure, 444
Prolotherapy, 1272, 1551–1552
Promethazine, for nausea/vomiting in cancer patients, 684t
PROMIS (Patient-Reported Outcomes Measurement Information System),
227, 467–468, 791, 792, 1313
PROMIS Global Health, 227, 232
PROMIS Measures of Physical Function, 227, 232
PROMIS Pain Interference, 227, 286, 287–288, 290
PROMIS Short Form Alcohol Use, 231
PROMIS Short Form Applied Cognition–Abilities, 227
PROMIS Short Form Depression, 229
PROMIS Short Form Emotional Distress–Anxiety, 227, 229, 914
PROMIS Short Form Pain Behavior, 227
PROMIS Short Form Physical Function, 232

5794
PROMIS Short Form Sleep, 227
Promoting Adequate Availability of Internationally Controlled Licit Drugs
for Medical and Scientific Purposes While Preventing Their
Diversion and Abuse (UN), 219
Pronator drift, 234
Pronator syndrome, 267, 1676
Pro-opiomelanocortin (POMC), 419
Propantheline, for oral mucositis prevention, 738
Propionic acid derivatives, 1316t, 1321–1322
Propofol
for baclofen withdrawal, 1764
for burn pain, 903
for cancer pain in children, 794
for emergency department use, 1778
for palliative sedation, 1739–1740, 1739t
Propoxyphene, 1346
Propranolol
for migraine, 990t
for migraine prevention, 1023t
for posttraumatic stress disorder, 444
for primary sex headache, 1028
Proprioceptive neuromuscular facilitation, 1482–1483
Propriospinal pathways, 43, 53
PROs. See Patient-Reported Outcomes
Prosopalgia. See Trigeminal neuralgia (classical)
Prostaglandin(s)
in cancer pain, 627, 681, 732–733
in muscle nociceptor activation, 508–509
NSAID inhibition of, 1315, 1326, 1327
Prostaglandin inhibitors, intrathecal, 1629
Prostaglandin receptors, 49
Prostanoids, 49
Prostate cancer, 640–641
chemotherapy for, 781
epidemiology of, 621, 622f, 640

5795
 Gleason grading of, 640
pain in, 640–641
bone metastases and, 634, 640, 744–747, 744t, 772–773, 776
causes of, 640, 640t
perineal, 640–641
tumor type and stage of disease in, 638
palliative radiation therapy for, 767
spinal cord compression in, 661, 772–773
Prostate gland, sympathetic and nociceptive nerve supply to, 117t
Prostate pain syndrome, 1098t, 1099, 1103–1104
Prostatic cancer, low back pain in, 1251
Prostatitis, 1099, 1103–1104
Protective factors, in pain, 77
Proteoglycan, 485
Protocol Amending the Single Convention on Narcotic Drugs (1972), 206
Proton pump inhibitor test, 1043–1045
Proton pump inhibitors (PPIs)
combined with NSAIDs, 1323–1324
for gastric protection with NSAIDs, 1327
for GERD-related chest pain, 1038, 1051, 1053
Provocation Inventory (PI), 1398t, 1399
Provocative disk injections, in failed back surgery, 1294
Provocative testing
in cancer pain, 611–613, 612t
in musculoskeletal rehabilitation, 1481–1482
in noncardiac chest pain, 1046
in thoracic outlet syndrome, 576–577
Provocative/palliative assessment (P), 228, 228f
PRP. See Platelet-rich plasma
Pruritoception, 543
Pruritus
neuraxial analgesia and, 836, 949
opioid-induced, 798, 816–817, 817t, 1341, 1637
PSA. See Procedural sedation and analgesia
PSEQ. See Pain Self-Efficacy Questionnaire

5796
Pseudoaddiction, 14, 459f, 1002t, 1004, 1518, 1773
Pseudoarthrosis, in failed back surgery, 1289, 1290t
Pseudoclaudication, 568
Pseudoephedrine, for priapism, 969
Pseudogout, 484, 497
Pseudomonas aeruginosa, in HIV/AIDS, 987
Pseudorheumatoid arthritis, 497
Pseudotolerance, 1003
Pseudotumor cerebri, 258
Psoas, in male pelvic pain, 1102
Psoas abscess, 1208
Psoas compartment block. See Lumbar plexus block
Psoriatic arthritis, 484, 496, 496f
PSQI. See Pittsburgh Sleep Quality Index
PSST. See Problem-solving skills training
pSTT. See Paleospinothalamic tract
Psychiatric functioning
and doctor–patient relationship, 476–477
evaluation of, 298–299
Psychiatric illness, 430–452. See also specific illnesses
behavior perspective on, 431
cognitive-behavioral therapy for, 1410–1411
in difficult patients, 476–477
dimension perspective on, 431
disease perspective on, 431
DSM criteria for, 430–432, 432f, 432t
framework for describing symptoms in, 432–433, 432f
life story in, 431–432
nosology and diagnostic/treatment approaches, 430–432
pain and suffering in, 448
referral to psychiatrist, 431
Psychiatry, 432
Psychodynamic theory, 437
Psychodynamic therapy, for depression, 439
Psychoeducation, chronic pain, 1406–1407

5797
Psychogenic conceptualizations, of chronic pain, 82
Psychogenic pain, 14, 16, 76, 82, 138, 430
biopsychosocial model v., 588
in cancer, 614–615
and conversion disorder, 447
Psychological aspects of pain, 76–89
in abdominal pain, 442, 1067, 1067f
anger in, 80, 81–82, 1392–1404
anxiety in, 79–80
anxiety sensitivity in, 77, 79–80
appraisal and beliefs in, 77–78, 84–85, 296
behavioral formulations of, 82–83
biopsychosocial model in, 85, 90–91, 91f
in burn injury, 899–900
in cancer, 629, 664
catastrophizing in, 13, 78
as causes v. consequences, 318–319
in chest wall pain, 1191, 1201t–1202t
in childbirth, 941, 942
in children, 912, 913–914, 914–915
cognitive factors in, 76–79
cognitive-behavioral model in, 83–85
as concomitants v. precursors, 319
consciousness in, 143–144, 147
coping in, 79
culture and, 141–143
depression in, 79–81
emotion in, 79–80
expectations in, 76, 84, 476, 1406–1407, 1726
family and family systems in, 85
fear-avoidance models in, 77, 78, 80, 225–226
IASP on, 138
illness/injury sensitivity in, 77
in low back pain, 1251
“medical limbo” and, 76

5798
 multidisciplinary assessment of, 318–323
in neck and arm pain, 1161
negative affectivity in, 77
in noncardiac chest pain, 1041, 1047, 1050
in pelvic pain
female, 1084–1085
male, 1103
perceived control and self-efficacy in, 78–79
predispositions in, 76–77
protective factors in, 77
psychogenic conceptualizations of, 82
in spinal cord injury, 588
stress and autonomic responses in, 79
in visceral pain, 752
Psychological evaluation, 295–301, 318–323
belief structures in, 296
brief (ACT-UP), 319, 319t
current functioning in, 296
early life experiences in, 295
educational history, 295–296
interviews for, 319–320, 320t
problems areas to assess, 321–323
psychiatric functioning in, 298–299
psychosocial history in, 295–296
screening for advanced interventional procedures, 299
social support in, 296
substance use in, 296–298
vocational history in, 295
Psychological flexibility, 77, 1410
Psychological interventions, 85–86. See also specific therapies
for abdominal pain, 1070
for anger, 1399–1401
for burn pain, 903–905
for central pain, 403
for chronic pain

5799
 in anxiety and depression, 1417–1418
in children, 918–919
group therapy, 1439–1469
for complex regional pain syndrome, 353–354
for failed back surgery, 1295
gender differences in, 94
for low back pain, 1272–1273, 1541
for male pelvic pain, 1104
for noncardiac chest pain, 1055
for phantom pain, 368
for postherpetic neuralgia, 390
for rehabilitation, 1499–1500
for spinal cord injury pain, 593
in spine clinics, 1718
Psychological interviews, 319–320, 320t
Psychological markers, 1425
Psychological theories, of depression, 437–438
Psychologist, 1711–1712
Psychometrics, in pain taxonomy, 22
Psychophysiology of pain, 410–424
emotion in
adaptive functions of, 411
autonomic arousal in, 413
and behavior, 411
central limbic processing in, 414, 414f
central neuroanatomy of, 412, 412f
central neurotransmitter systems in, 414, 414f
and cognition, 410, 417–418
construction and modulation of pain, 417
feedback in, 413
HPA axis in, 413–414, 416–417, 416f
locus coeruleus and dorsal noradrenergic bundle in, 414–415, 414f
noxious signaling in, 413–417, 414f, 416f
peripheral neuroanatomy of, 412–414
relationship between central and peripheral mechanisms in, 413–414,

5800
 413f
sociobiologic perspective on, 411
ventral noradrenergic bundle in, 414, 414f, 416–417
future directions in, 421
historical perspective on, 410–411
sense of self in, 418
stress in, 418–421
and chronic pain, 420–421
immune mechanisms of, 419–420
neural substrates of, 419
physiologic mechanisms of, 419–420
sickness response in, 420
Psychosocial adaptation, assessment of, 322–323
Psychosocial factors
assessment of, 230, 318–323
in chronic pain in children, 914
in neck and arm pain, 1161
in spinal cord injury, 581, 583t, 588
Psychosocial history, 295–296, 1161
Psychotherapy
for anger, 1399–1401
for depression, 439–440
Psychotropic drugs, for cancer pain, 687
PTN. See Painful trigeminal neuropathy
PTS. See Posttraumatic syringomyelia
PTSD. See Posttraumatic stress disorder
Public health, unrelieved pain as problem in, 172
Public Health Service Act, 178
Pudendal nerve
anatomy of, 1205, 1207f
in female pelvic pain, 1090, 1090f
in male pelvic pain, 1099, 1102, 1103
Pudendal nerve block, for childbirth pain, 940, 951
Pulmonary embolism, 1194t
Pulmonary hypertension, 1194t

5801
Pulmonary pain, in HIV/AIDS, 987
Pulpitis, 1131t
Pulse generator, for spinal cord stimulation, 1580–1581
Pulse oximetry, 1778
Pulsed electromagnetic field therapy (PEMF), for elderly patients, 934
Pulsed infrared light therapy (PILT), 1525
Pulsed radiofrequency
for postherpetic neuralgia, 389
for residual limb pain, 368
Punctate/pinprick, 235
Pupil constriction, opioid analgesics and, 1338
Purdue Pegboard Test, 1502
Purdue Pharma LP, 199
Putative energy therapies, 1552–1554
PVBs. See Paravertebral nerve blocks
PVN. See Paraventricular nucleus
Pyoderma gangrenosum, 551–552, 551f
Pyridoxine deficiency, isoniazid use and, 331–332

Q
Qi, 1552, 1554
QLB. See Quadratus lumborum block
QOL. See Quality of life
QSART. See Quantitative Sudomotor Axon Reflex Testing
QST. See Quantitative sensory testing
Quackery, 1546
Quadratus lumborum block (QLB), 883–885
Blanco’s optimal point of injection, 883, 884f
clinical effects of, 885
complications of, 885
indications for, 883
shamrock, 883, 884f
ultrasound techniques in, 885, 885f
Qualitative systematic review, 133
Quality of life (QOL), 14, 1313
cancer and, 623, 628–629, 664, 733–734, 763

5802
 cancer in children and, 791
chronic pain in children and, 910, 912, 914, 920
definition of, 912
end-of-life care and, 1734
headache and, 910
neuropathic pain and, 1359, 1375
noncardiac chest pain and, 1035, 1041
pain in elderly and, 929
postoperative pain and, 843
postoperative pain management and, 843
research on, 1313
Quality of Life in Reflux and Dyspepsia (QOLRAD), 1051
Quality of pain, 228, 228f, 321
in cancer, 664
in central pain states, 397–398, 398t
in cervical radiculopathy, 1173
in childhood cancer, 790, 791
description of, 278
as descriptive and outcome measure, 279–285
as diagnostic aid, 278–279
in failed back surgery, 1293
low back, 1250
measurement of, 278–285, 290
in neck and arm pain, 1160
in neuropathic pain, 1359
strengths and weaknesses as measure, 285
in vascular disorders, 566
Quality of study or review, 127, 127t, 133, 133t
Quantitative sensory testing (QST), 235, 330, 1683
in fibromyalgia, 529
gender differences in, 842
in neuropathic pain, 235–236, 330, 1359
in postherpetic neuralgia, 381, 382
in spine surgery candidates, 1301
Quantitative Sudomotor Axon Reflex Testing (QSART), 330

5803
Quantitative systematic review, 133
Quantity, of prescription, 179, 181–182, 181t, 182t
Questionnaires, pain. See also specific questionnaires
follow-up, 241
initial visit, 236–240
multidimensional, for persistent pain history, 227–228
nonproprietary, 227
outline of, 227
proprietary, 227–228
Quinine, 8
Quota programs, for exercise, 1539
Quotas, for controlled substances, 177

R
Rabeprazole, 1044, 1053
Racial differences. See Ethnic group differences, in pain
RADARS. See Researched Abuse, Diversion and Addiction-Related
Surveillance (RADARS) system
Radial nerve
anatomy of, 1147, 1148f, 1149f, 1153t–1154t
evaluation of, 1482, 1482f
Radial nerve block, 863–866, 864f, 865f, 866f
Radial nerve entrapment, 1676–1677
Radial tunnel syndrome, 1676
Radiation cystitis, 757
Radiation enteritis, 755, 756–757
Radiation myelopathy, 658–659
Radiation neuropathy, 658–659
Radiation plexopathy, 655, 658–659, 1207
Radiation proctitis, 756–757
Radiation therapy
barriers to, 765
for bone metastases, 765, 767–778, 768t, 769f, 770
diffuse, 776–778
Karnofsky performance states and survival in, 769–770, 769f
pathologic fracture in, 770–772, 771f

5804
 reirradiation in, 770
response to, 767–768, 768t
single-fraction, 768–770
spinal cord tolerance of, 774–776
vertebral (spinal cord compression), 773–776, 775f
wide-field, 776–777
and cancer pain, 635
in cancer pain management, 763–778
curative v. palliative, 766
tumor response in, 766–768
clinical applications of, 766
cost of, 765
in head and neck cancer, 733, 735–736, 736f
and oral mucositis, 661, 735–737, 736f, 754, 796
pain mechanisms due to, 635, 646t, 658–659, 733
pain mechanisms in, 733
and visceral pain, 756–757
Radiation Therapy Oncology Group (RTOG), 767–769, 777
Radiation therapy–induced nausea and vomiting (RINV), 683
Radiation-induced brachial plexopathy (RBP), 655, 656t
Radicular pain, 566, 1246, 1246f, 1259–1260
cancer-related, 653–654, 656, 662
epidural steroid injections for, 1611–1622
neck, 1138
quality of, 1250
site of, 1249–1250
Radiculopathy
cancer-related, 653–654
cervical, 1138, 1161t, 1172–1173, 1485
chest wall pain in, 1197t
coexisting conditions with, 1161t
electrodiagnostic tests in, 249
MRI findings in, 249
Radiofrequency intradiscal ablation, 1646–1647
Radiofrequency intradiscal thermocoagulation, 1647–1648

5805
Radiofrequency myelotomy, 728, 729f
Radiofrequency neurotomy, 1653, 1655–1664
for ankylosing spondylitis, 1188
applications of, 1656–1664
for brainstem procedures, 1657
for central ablative procedures, 1656–1657
cervical medial branch, 1171, 1238–1239, 1239f, 1660–1662, 1661f
for cordotomy, 1657
for discogenic pain, 1295
for dorsal root entry zone lesions, 1657
efficacy of, 1555t
for intercostal neuralgia, 1186
limitations of, 1653–1654
lumbar medial branch, 1275–1276, 1275f, 1278–1279, 1657–1660,
1659f
occipital, 1239–1240, 1240f, 1662–1663, 1663f
pathology of, 1656
physics of, 1654–1655, 1655f, 1656f
physiology of, 1656
sacral lateral branch, 1663–1664
for thoracic facet syndrome, 1188
for trigeminal neuralgia, 1115–1116, 1656
Radiofrequency rhizotomy, for trigeminal neuralgia, 1691, 1694–1695,
1695f
Radiography
of acute chest syndrome, 964, 964f
of ankylosing spondylitis, 494, 494f, 1188
in bone cancer, 745
of cervical spine, 1168–1169, 1167t, 1168f
dental, 1131, 1131f
of diffuse idiopathic skeletal hyperostosis, 1188
in failed back surgery, 1294
of gout, 499, 499f
in low back pain, 1252–1253, 1252t
of metastatic spinal cord compression, 772

5806
 of osteoarthritis, 489, 489f
of pathologic fracture, 771, 771f
of reactive arthritis, 495
of thoracic outlet syndrome, 267, 578, 578f
of vertebral fracture, 1187
Radionuclide examinations, 251
Radiopharmaceuticals, for bone pain in cancer, 747, 765, 777–778, 777t
Radiosurgery. See Stereotactic radiosurgery
Radiotracer, 62
Raich, Angel, 202
Raj, Prithvi, 1751
Raman spectroscopy, 1017
Ramsay-Hunt syndrome, 373
Ramus communicans lesions, 1646–1647
Rancho Los Amigos Hospital, 1501
Randomized trial, 126
Range of motion (ROM), 1481, 1483
RANKL. See Receptor activator of nuclear factor-κB ligand
Raphe nuclei, 63
Rash, in herpes zoster, 372, 373f, 374
Rating scales, 16, 276, 276f. See also specific rating tools
Ratings of Perceived Exertion, 1502
Rational pharmacotherapy, 1314
Rational polypharmacy, 1312
Raynaud phenomenon, 570
Raynaud syndrome, 570, 578
RBP. See Radiation-induced brachial plexopathy
rCBF. See Regional cerebral blood flow
RDC. See Research Diagnostic Criteria
RDQ. See Reflux Disease Questionnaire
Reactive arthritis, 484, 495–496, 987, 1247
Reactive depression, 434
Reactive oxygen series (ROS), in myofascial pain, 511
Reappraisal techniques, for burn pain, 904
Rebound tenderness, 1064

5807
Recall ratings, 274–276
Receptive fields, 52, 235
Receptor activator of nuclear factor-κB ligand (RANKL), in bone
metastases and pain, 647, 745, 746, 794
Recombinant nerve growth factor, for HIV pain, 996
Recovery, 77
Recreational therapist, 1712
Recreational therapy, for complex regional pain syndrome, 351
Rectal acetaminophen, 1323, 1324f
Rectal interventions, for opioid-induced bowel dysfunction, 683
Rectal lidocaine, 1070
Rectal opioids, 1342–1343, 1342t, 1735
Rectal route, for end-of-life drug delivery, 1735
Rectal spasms, adjuvant analgesics for, 686–687
Rectum, sympathetic and nociceptive nerve supply to, 116t
Rectus sheath block, 856, 856f
Recurrent pain, definition of, 11, 12
Red flags
in low back pain
acute, 1247–1249, 1249f, 1251, 1253, 1256
chronic, 1259, 1262, 1263
in multidisciplinary assessment, 314–317
in neck pain, 1161t
in spinal cord injury, 585–586, 586t
Reductionist medicine, 1546
Reed’s syndrome, 560
Referred pain, 103–104, 566, 1063, 1063f, 1066
arm and neck, 1160
cancer, 602, 662
from cervical spine, 1230–1231, 1230f, 1231f
chest wall, 1191, 1192f, 1200t–1201t
low back, 1245, 1250, 1259–1260
low back somatic, 1246, 1246f
visceral, in cancer, 652
Reflection

5808
 amplified, 1475
double-sided, 1475
simple, 1475
Reflective listening, 1728
Reflex(es), 234t, 425
Reflex neurovascular dystrophy. See Complex regional pain syndrome
Reflex paralysis, 8
Reflex sympathetic dystrophy. See Complex regional pain syndrome
Reflex testing, 1163, 1164t
Reflux Disease Questionnaire (RDQ), 1051
Regional analgesia (anesthetics), 1384–1387. See also Epidural analgesia;
Nerve blocks; specific techniques
for acute pain, 833–837, 850–896
block technique for, 850–851
combined spinal-epidural, 852
continuous epidural, 833–836, 850–851
contraindications to neuraxial techniques in, 853
dosage recommendations for, 833t
epidural medications for, 833–834
intra-articular, 837
local anesthetic–opioid combination in, 834
outcome studies of epidural analgesia, 835–836
patient-controlled epidural, 835, 836t
peripheral, 836–837
risks of epidural analgesia, 836
side effects of neuraxial drugs in, 834–836, 835–836
single-dose neuraxial opioids in, 833, 833t
subarachnoid/intrathecal, 833, 851–852
thoracic epidural, 850, 850t
in war trauma, 838
for childbirth, 940, 946–951
for children, 817
differential blockade in, 1384–1385
injection sites for, 1385
in intensive care unit, 1787–1788

5809
 intravenous, 1386
Regional cerebral blood flow (rCBF), 62–63
Region/radiation of pain (R), 228–229, 228f
Regression to the mean, 124, 124f
Regulatory barriers, in pain management, 172–173, 216–217, 217t, 1725–
1726
Rehabilitation, 1490–1507, 1491. See also Physical therapy; specific
modalities
activities in, 1496–1501
acute, 1493
assessment in, 1495
barriers to collaboration in, overcoming, 1495, 1496f
behavioral approaches in, 1497
biomechanics in, 1480–1489
biomedical model of, 1491
biopsychosocial risk factors for, 1491
case management in, 1495
for children with chronic pain, 920
cognitive-behavioral therapy in, 1411, 1494, 1496, 1497t, 1499–1500
for complex regional pain syndrome, 350–351
continuum of care in, 1493, 1494f, 1495
definition of, 14, 1490, 1491
exercise prescription in, 1498
exercise therapy for, 1497–1498, 1498t
for failed back surgery, 1294
functional capacity testing in, 1498, 1501–1503
goals of, 1493, 1493t, 1496
historical overview of, 1490–1492, 1492t
interdisciplinary approach in, 1493, 1494–1495, 1494f
manual therapy in, 1497, 1497t
models of, 1492–1495
biomedical, 1491, 1492–1493
biopsychosocial, 1490, 1492–1493, 1492f, 1493f
conceptual, 1496–1501
team, 1493, 1494f, 1495, 1496

5810
 motivation in, 1470
multidisciplinary approach in, 324, 1493–1495, 1494f
occupational therapy in, 1498–1499
opioid management in, 1503–1504, 1504t
outcomes of, 1494–1495
patient perceptions in, 1495–1496, 1496t
patient-centered approach in, 1492–1493
physical therapy in, 1497
principles of, 1495–1496
psychological interventions in, 1499–1500
stakeholders in, 1491–1492, 1495
success criteria in, 1491, 1491f
team building in, 1495
team values in, 1495
treatment approaches in, 1493–1495, 1493t
work, 1501, 1501t, 1502t, 1503t
Rehabilitation cycle, 1495, 1495f
Rehabilitation specialists, 1496–1501
building therapeutic relationship, 1496
conflicting roles of, 1491, 1492t
Rehabilitative model, of cancer pain, 615, 616f
Reiki, 1554, 1555
Reinforcement, 82–83, 426
in chronic pain, 427
in Fordyce pain studies, 426–427
in low back pain, 1247, 1256
Reinforcement management, 1472t
Reinforcement schedules, 426
Reirradiation, 770
Reiter’s syndrome. See Reactive arthritis
Relapse prevention, 1406, 1409–1410, 1512
Relapsing polychondritis, 558
Relaxation, in hypnotic analgesia, 1423, 1433
Relaxation techniques
for burn pain, 904–905

5811
 for cancer pain, 701
for chronic pain, 1406, 1407–1408
for complex regional pain syndrome, 353
group cognitive-behavioral therapy v., 1455
for herpes zoster, 379
for phantom pain, 368
for prostate pain syndrome, 1104
for rehabilitation, 1500–1501, 1500t
for sickle cell disease pain, 973
for tension-type headache, 1133
Reliability, 22, 273
Relieving Pain in America (IOM), 153, 185, 296, 1793
Religion, 143, 802
Remifentanil, 902, 903, 1786
Remodeling phase, in burn injury, 898–899
REMS. See Risk evaluation and mitigation strategy
Renal cell carcinoma, 642
Renal failure
and NSAID therapy, 1318
and opioid therapy, 687–688, 688t
Renal toxicity, of NSAIDs, 1327–1328
Reperfusion injury, in sickle cell disease, 958
Repetitive nerve stimulation studies (RNS), 245, 246f
Repetitive transcranial magnetic stimulation (rTMS), 1587, 1591–1592
basic considerations in, 1591–1592
efficacy of, 1592
for fibromyalgia, 538
for phantom pain, 367
procedure for, 1591, 1591f
Report card, on state pain policies, 182–185, 184t
Report of the International Narcotics Control Board on the Availability of
Internationally Controlled Drugs: Ensuring Adequate Access for
Medical and Scientific Purposes (INCB), 219
Reports, clinical trial, 129
Research Diagnostic Criteria (RDC), 15, 22, 630

5812
Researched Abuse, Diversion and Addiction-Related Surveillance
(RADARS) system, 175–176
Residency, in pain medicine, 1751–1754
Residual functional capacity, 14
Residual limb pain, 363, 368
Residual pathology, and failed back surgery, 1289–1290
Resilience, 14, 77
Resistance
to behavioral change, 1474–1475, 1475t
in primary care, 1725
Respiration, in biofeedback, 1500, 1500f
Respiratory changes, in pregnancy, 943, 943t
Respiratory depression
neuraxial analgesia and, 949
opioid analgesics and, 1337–1338
Respiratory diseases, chest pain in, 1194t–1195t
Respondent conditioning, 82
Responder analysis, 129
Response sensitization, 415
Rest pain, 569–570
Resting pain, in burn injury, 898
Results, clinical trial
generalizability of, 130
reporting, 129
Resuscitative phase, in burn injury, 898
Retail level, opioid diversion at, 187
Retention times, in urine drug testing, 1015t
Reticular activating system, 63, 70
Reticular formation, 63
Reticulospinal tract, 40f
Retrograde embolism, in acute chest syndrome, 964–966
Retroperitoneal hematoma, 1208
Retroperitoneal pain, 1062–1063
Retroperitoneal pain stretch maneuver, 613, 614f
Retrospective studies, 123–124

5813
Retrosplenial cortex, 67
Return to work, 445, 1255, 1491, 1501
Reuleaux, Franz, 1480
Revascularization, 572–573
Reverse breathing, 1500, 1500f
Reversed arm levitation induction, 1432
Revised Child Anxiety and Depression Scale, 914
Revised Screener and Opioid Assessment for Patients with Pain (SOAPP-
R), 700
Reward pathway, in addiction, 1002–1003, 1003f
Rexed classification, of spinal laminae, 39–42, 41f
Reye syndrome, 810, 1320
Rhenium-186, for bone pain in cancer, 747, 777–778, 777t
Rheumatoid arthritis, 490–493
complications of, 493
epidemiology of, 484, 490
etiology of, 490
fibromyalgia with, 527, 532
group therapy for, 1447t, 1448t, 1453t, 1457t, 1459t
heat therapy for, 1523
juvenile, 811, 909, 917
laboratory findings in, 491
laser therapy for, 1524–1525
low back pain in, 1251
neck pain with, 1233
nerve entrapment with, 491, 493, 1175, 1672
pain narrative in, 143
pathophysiology of, 490
pattern recognition in, 486
physical findings in, 491, 491f
smoking and, 490
symptoms and signs of, 490–491, 491f
treatment of
anti-TNF agents in, 492–493, 492t
current management in, 492–493

5814
 DMARDs in, 491–493, 492t
glucocorticoids for, 493
philosophy of, 491–492
pyramid of, 491
surgical, 493
Rheumatoid vasculitis, 493, 545t, 547–548
Rhinogenic headache, 1134
Rhizotomy
for cancer-related bone pain, 748
for cluster headache, 1134
dorsal, 1668, 1678–1682, 1679f
facet, 1668
percutaneous, for trigeminal neuralgia, 1691, 1694–1695, 1695f
trigeminal radiofrequency, 1115–1116
Rib(s)
anatomy of, 1180, 1181f, 1183f
chest wall pain from disorders of, 1188–1189, 1198t
Rib fractures, 1188–1189
Riboflavin, for headache prevention, 922, 1023t, 1133
“The Riddle” of disease, 152, 155
Rifampin, for hidradenitis suppurativa, 555
“Right patient,” for spine surgery, 1292–1293
Rigidity, 234
Riluzole, for neuropathic pain, 1368t
Rimegepant, for migraine, 1024
Risk evaluation and mitigation strategy (REMS), 175, 694, 1012, 1771
Risk mitigation strategies, for opioids, 465, 465t
Rituximab
for ANCA vasculitis, 547
for antiphospholipid syndrome, 548
for bullous pemphigoid, 558
for epidermolysis bullosa, 558
for leukocytoclastic vasculitis, 546
for pemphigus vulgaris, 557
for rheumatoid arthritis, 492t, 493

5815
Rizatriptan, 922, 991t, 1024t
RNA interference (RNAi), 757
Robert Bree Collaborative, 308
Rofecoxib, 811, 1324
Roggow, Debra, 201
Roland-Morris Disability Questionnaire, 129, 302–303, 1305, 1613
ROM. See Range of motion
Rome IV Committee criteria, for chest pain, 1034, 1035t
Roos test, 577, 1166
Ropivacaine, 1386t
dosing in nerve blocks, 888t
epidural
for acute pain, 834
for childbirth pain, 947t, 948, 949t
for children, 818–819, 819t
intrathecal, 1626
for phantom pain, 366
for trigger point injections, 516
Rose, Nikolas, 137, 140, 145
Rosen, Isadore, 199–200
Rostral agranular insular cortex, 57
Rostral ventral medulla (RVM)
in acute pain, 827, 831
in depression–pain association, 436
in descending modulation of pain, 54–56, 55t, 56f
in hyperalgesia, 58–59
in neuropathic pain, 59
ON, OFF, and NEUTRAL cells in, 57–58
in opioid-induced hyperalgesia, 59
opioid-induced hyperalgesia and, 457
in spinal cord stimulation, 1572
in stimulus-induced analgesia, 64
in stress, 419
in stress-induced analgesia and hyperalgesia, 59
Rotation, of opioid analgesics, 698, 698t, 799, 1312, 1339–1340, 1349,

5816
 1737
Rotator cuff pathology, 1150, 1155f, 1156f
Rotterdam Symptom Checklist, 630, 1734
Rovenstine, Emery, 9
Royal College of Anaesthetists (United Kingdom), 1755
RSD. See Complex regional pain syndrome
rTMS. See Repetitive transcranial magnetic stimulation
RTOG. See Radiation Therapy Oncology Group
Rubefacients, 1357
Rule of double effect, 168–169
RVM. See Rostral ventral medulla
Rynd, F., 8

S
Sacral chordomas, 1207
Sacral insufficiency fractures, 649–650, 651f
Sacral lateral branch blocks, 1268–1269, 1277, 1279
Sacral lateral branch neurotomy, 1663–1664
Sacral nerves
studies of, 246
tumor infiltration of, 656
Sacral pain, dorsal rhizotomy or ganglionectomy for, 1680–1681, 1681f
Sacral parasympathetics, 111, 112f, 113f
Sacral plexus, 1205, 1206f, 1207f. See also Lumbosacral plexopathy;
Lumbosacral plexus
Sacral plexus-sciatic nerve block, 877–882
anterior approach in, 878, 879, 879f
for children, 820–821
classic Labat approach in, 878, 878f
clinical effects of, 879–882
complications of, 882
indications for, 877
landmarks for, 877–878, 878f, 879f, 880f
popliteal fossa approach in, 878, 879, 880f
subgluteal approach in, 878, 879f
techniques for, 878–879

5817
 ultrasound guidance for, 878–879
alternative technique in, 879
classic technique in, 878–879, 880f, 881f
lateral technique in, 879, 881f
Sacral spinal pain, 1245f. See also Low back pain
Sacroiliac joint blocks, 1268, 1270f, 1605–1606, 1606f
Sacroiliac joint pain, 1089, 1276–1277
biomechanical considerations in, 1487–1488
in failed back surgery, 1290, 1290t, 1291, 1291t, 1294, 1295
treatment of, 1276–1277, 1279, 1295
Sacrum, tumor infiltration of, 656
SAFE-T. See Suicide Assessment Five-Step Evaluation and Triage
Safety, in prescription monitoring, 182
SAH. See Subarachnoid hemorrhage
Salbutamol, for rectal spasm, 686
Salicylates, 810, 1316t, 1320. See also Aspirin
topical, 1356–1357
Salivary glands
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Salsalate, 932, 1316t
SAM. See Sympathoadrenomedullary (SAM) axis
Samarium-153, for bone pain in cancer, 747, 765, 777–778, 777t
Samter’s triad, 1326
Saphenous nerve, 882, 1205, 1206f, 1212, 1212f
Saphenous nerve block, 1214
Saphenous nerve entrapment, 1212, 1213–1214, 1678
diagnosis of, 1214
etiology of, 1212
signs and symptoms of, 1213
treatment of, 1214
Saphenous neuralgia, 1670
SAPHO syndrome, 1188
Sarcomere, 506, 507f
Sarcoplasmic reticulum, 506

5818
Sargramostim, pain from, 795
Sarilumab, for rheumatoid arthritis, 492t
Sativex spray, for central pain, 401t
Saturnine gout, 498
Saunders, Cicely, 7, 7f, 1732
Sausage digits (dactylitis), 493, 494f
Scalene muscle block, for thoracic outlet syndrome, 578, 579
Scandinavian Society of Anaesthesiology and Intensive Care Medicine,
1755
Scapula
anatomy of, 1150–1158, 1155f
movement of, 1156, 1157f
Scapulothoracic interface, 1150, 1156
Scarry, Elaine, 410
SCB. See Supraclavicular block
SCCM. See Society of Critical Care Medicine
SCD. See Sickle cell disease
SCEH. See Society for Clinical and Experimental Hypnosis
Schedule I medications, 176–177
Schedule II medications, 176–177
Schedule III medications, 176–177
Schedule IV medications, 176–177
Schedule V medications, 176
Schiff, Moritz, 4
Schloesser, H., 9
Schober test, modified, 494
Schofield, Penelope, 162
School reintegration, 919–920
School-age children
cancer pain in, 788–789
chronic pain and school experience for, 914
Schwannoma, 265f, 560, 561t
SCI. See Spinal cord injury
Sciatic nerve
anatomy of, 877–878, 1205, 1206f, 1207f, 1215–1216, 1215f, 1216f

5819
 relationship with piriformis muscle, 1215, 1216f
Sciatic nerve block. See Sacral plexus-sciatic nerve block
Sciatic nerve entrapment, 1215–1217, 1677–1678
diagnosis of, 1217
etiology of, 1216
signs and symptoms of, 1216–1217
treatment of, 1217
Sciatic terminal branches, 882
Sciatica, 1246
Sciatic-subgluteal approach, for children, 820
SCIPI. See Spinal Cord Injury Pain Instrument
SCL-90-R. See Symptom Checklist 90
Scleroderma, chest pain in, 1200t
Sclerotomal pain, 602, 612–613, 1160
Sclerotomes, 1145, 1150f, 1152t
Scoliosis, chest wall pain in, 1187
Scopolamine, for nausea/vomiting in cancer patients, 684t
SCORTEN, 556
Scrambler therapy, for postherpetic neuralgia, 390
Screener and Opioid Assessment for Patients with Pain (SOAPP), 227,
231, 700, 1006
Screening Instrument for Substance Abuse Potential (SISAP), 227, 231
Scrotal pain syndrome, 1098t, 1099, 1104
SCS. See Spinal cord stimulation
Sealant, intradiscal, 1649
Secondary dysmenorrhea, 1083
Secondary fibromyalgia, 527–528
Secondary gain, 447
Secondary gout, 498
Secondary headache, 1019, 1020–1021, 1031, 1031t, 1134–1135
Secondary osteoarthritis, 487, 489
Secondary somatic hyperalgesia, 753
Secondary somatosensory cortex, 65, 66f, 67, 412
Secondary trigeminal neuralgia. See Painful trigeminal neuropathy
Second-degree burns, 897, 898f

5820
Second-order neurons, 26, 38–51
excitation of, 52–53
functional characterization of, 42–43
inhibition of, 52–53
intraspinal pathways of, 43
modulation of, 52–61
spinal cord-based, 52–53
supraspinal, 53–58
neurochemistry of, 45–50
receptive fields of, 52, 235
site of projection, classification according to, 43
spinal laminae, 39–42
spinomesencephalic, features of, 45
spinoreticular, features of, 44–45
spinothalamic tract
functional characterization of, 44, 107
laminar distribution of, 43–44, 107
targets of axonal projections, 43–45
targets of primary afferent inputs, 39–43
in visceral pain, 1065–1066
Secukinumab, for psoriatic arthritis, 496
Security, feeling of, 479–480, 479t
Sedation
for burn pain, 900–901, 900t, 901t, 903
depth of, 900, 900t
for dying patient, 168–169, 1739–1740, 1739t
emergency department, 1775, 1777–1778
intensive care unit, 1782, 1788–1789
for nerve blocks, 1596
opioid analgesics and, 1337
opioid-induced, in children, 816–817, 817t
for pediatric cancer patients, 794
Sedative-hypnotics
for cancer pain, 687
for fibromyalgia, 537

5821
 as muscle relaxants, 1352t, 1354
for tension-type headache, 1133
Segmental modulatory effects, acute, 52, 52f
Seizures
dying and, 1737
local anesthetic-induced, 887, 1763, 1763f
Selective attention, 70
Selective consciousness, 1422
“Selective” receptors/channels, 50
Selective serotonin reuptake inhibitors (SSRIs)
for abdominal pain, 1070
for acute pain, 831
for anxiety, 441, 442
for children, 917–918
for depression, 436, 439, 1416–1417
for dysthymic disorder, 435
for fibromyalgia, 535, 537t
for HIV pain, 995–996
for low back pain, 1271
for male pelvic pain, 1105
for neuropathic pain, 1359, 1360t, 1361t, 1362
for noncardiac chest pain, 1052–1053
for posttraumatic stress disorder, 444
for spinal cord injury pain, 591
Selectivity theory, 543
Selegiline, 438
Self
essence of, 1422
sense of, 418
Self-determination, 166
Self-efficacy, 78–79, 83, 322–323, 1305
in behavioral change, 1471
definition of, 1471
group therapy and, 1461
poor, 437

5822
Self-identification, ethnic, 140
Self-liberation, 1472t
Self-management, goals for, 1729
Self-motivational statements, 1474
Self-reevaluation, 1472t
Self-Report LEEDS Assessment of Neuropathic Symptoms and Signs (S-
LANSS), 278, 290
Self-report measures, 129, 320–321. See also specific measures
in childhood cancer, 790
in depression, cancer-related, 630
in functional assessment, 323
in substance use, 1509–1510
Selye, H., general adaptation syndrome of, 79
sEMG. See Surface electromyography
Seminal vesicle
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Semispinalis capitis, 1141, 1143f
Semispinalis cervicis, 1141, 1143f
Seneca, on anger, 1392
Senna, 798–799
Sensation
assessment of, 235–236, 282f–284f, 285
increased, 235
reduced, 235
Sense of self, 418
Sensitization
central (See Central sensitization)
nociceptor, 32–33
peripheral (See Peripheral sensitization)
visceral, 752
Sensory areas
cortical, 55t, 66–67, 66f, 108
nerve root, 234t
Sensory avoidance, signs of, 233

5823
Sensory exam, in neck pain, 1163
Sensory experience, of pain, 225
Sensory mononeuropathies, 559
Sensory nerve action potential (SNAP), 244, 244f, 1673
Sensory nerve conduction studies (SNCS), 244, 244f, 245f
Sensory neuronopathies, 335, 988
Sensory sensitivity syndromes, 525
Sensory systems, development of, 39
Sensory testing
bedside method for, 235–236
caveats to, 236
in central pain states, 398
in fibromyalgia, 529
gender differences in, 842
grading, 235–236
in neuropathic pain, 235–236, 330, 1359
in postherpetic neuralgia, 381, 382
in spine surgery candidates, 1301
Sensory-discriminative system, 65, 83
Sensory-level stimulation, 1526–1527
Separate needles technique, of combined spinal-epidural analgesia, 852
Sepsis, neuraxial techniques and, 852–853
Septic arthritis, 493, 500–501, 987
Septum, in emotion, 412, 412f
Serialized forms, 174
Seroma, intrathecal drug delivery and, 1634–1635
Serotonin, 45, 46t, 49
in abdominal pain, 1067, 1071
in acute pain, 827, 831
in anger (negative emotions), 1394
in brainstem, 63
in cancer pain, 732
in depression, 435, 436
in descending modulation of pain, 54, 55, 55t, 57, 60
in emotion, 414

5824
 in myofascial pain (trigger points), 508–509, 511
in neuropathic pain, 59
in spinal cord stimulation, 1571–1572, 1572f
in stress-induced analgesia and hyperalgesia, 59
in substance use disorder, 469
in suicide, 469
in vascular occlusive crisis, 960
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
for abdominal pain, 1070
for acute pain, 831–832
for anesthesia dolorosa, 1123
for anxiety, 441
for central pain, 400–402, 402f
for chemotherapy-induced peripheral neuropathy, 686
for children, 917
for complex regional pain syndrome, 352
for depression, 438–439, 1416–1417
for elderly patients, 933
for fibromyalgia, 535, 536t
for HIV pain, 994t, 995–996
for male pelvic pain, 1105
for migraine, 990t
for neuropathic pain, 400–402, 686t, 1359, 1360t, 1361–1362, 1361t
for noncardiac chest pain, 1053
for painful neuropathies, 336, 337
for postherpetic neuralgia, 384t, 386
for spinal cord injury pain, 591
Serotonin antagonists. See also Selective serotonin reuptake inhibitors
for abdominal pain, 1071
for nausea/vomiting in cancer therapy, 684
for trigger point injections, 516
Serotonin receptor agonists, for migraine, 1024
Serous mucosa, tumor infiltration and inflammation of, 638
Serratus anterior plane block, 885–886
clinical effects of, 886

5825
 indications for, 885
for rib fracture pain, 1189
ultrasound guidance for, 886, 886f
Sertraline
for depression, 439
for fibromyalgia, 537t
for neuropathic pain, 1360t
for noncardiac chest pain, 1053, 1055
for tension-type headache, 1133
Serturner, F., 8
Sesamoiditis, 1223–1224
Setbacks, in behavioral change, 1474–1475
Severity of pain
in cancer, 636, 664
classification based on, 16
evaluation of, 228–229, 228f
in neck and arm, 1160
in vascular disorders, 566
Sevoflurane, for burn pain, 903
Sex and gender differences. See Gender differences, in pain
Sexual abuse, and pelvic pain, 1084, 1099, 1100
Sexual intercourse
painful (dyspareunia), 1090–1091, 1091t
primary headache in, 1028
SF-MPQ. See Short-Form McGill Pain Questionnaire
Shamrock lumbar plexus block, 883, 884f
SHCS. See Stanford Hypnotic Clinical Scale
Shealy, C. Norman, 1558, 1570
Sherrington, Charles S., 5–6, 6f, 24, 1679
Shifting focus, 1476
Shingles. See Herpes zoster; Postherpetic neuralgia
Shingles Prevention Study, 380
Shockwave emitters, for trigger points, 515
Short Form-36, 129, 323, 1051, 1304–1305, 1313, 1630
Short interfering RNA therapeutics, 757

5826
Short-acting opioids, 689–690, 696, 1342
Short-Form McGill Pain Questionnaire (SF-MPQ), 228–229, 276–280,
277f, 285, 290, 321, 992
Short-lasting unilateral neuralgiform headache attacks with conjunctival
injection and tearing (SUNCT), 1026, 1026t, 1027, 1113, 1135
Short-lasting unilateral neuralgiform headache attacks with cranial
autonomic activation (SUNA), 1026, 1026t, 1027, 1135
Short-term memory, 1422
Shoulder
anatomy of, 1150–1158, 1155f, 1156f, 1157f
common disorders of, 1150, 1155f, 1156f
frozen, 658, 748
movement at, 1158, 1158f, 1159f, 1159t
Shoulder brace position, 577
Shoulder depression and abduction test, 1166
Shoulder impingement, 1150, 1155f, 1157
Shoulder pain
nerve blocks for, 1607
physical examination in, 1162, 1166
after spinal cord injury, 582–583
Shoulder syndrome, 658
Shoulder–hand syndrome. See Complex regional pain syndrome
SHSS. See Stanford Hypnotic Susceptibility Scale
SIA. See Stress-induced analgesia
Sick role, 445
Sickle cell disease (SCD), 955–984
acute abdominal pain syndromes in, 966–968
acute splenic sequestration crisis, 967–968
biliary sludge, 966
cholecystitis, 966
choledocholithiasis, 966
cholelithiasis, 966
hepatic crisis, 967, 967f
hepatic sequestration, 967
intrahepatic cholestasis, 967

5827
 left upper quadrant, 967–968
right upper quadrant, 966–967
acute chest syndrome in, 956, 964–966
definition of, 964
diagnostic testing in, 965
embolism, infarction, and necrosis in, 964–966, 964f, 965f
management of, 965–966
radiographic findings in, 964, 964f
risk factors for, 964, 964t
acute multiorgan failure in, 969
adhesion to vascular endothelium in, 958
avascular necrosis in, 969–971, 970f
cellular dehydration in, 957–958
in children
acute pain in, 822
chronic pain in, 909, 911, 912, 919
complications of, 956f
curative therapies for, 977
in emergency department, 1774–1775
fetal hemoglobin induction for, 975, 975t
gene therapy for, 977–978
genetic markers of, 958, 959f, 959t
genotypes of, 956, 956t
history of, 955
hydroxyurea for, 975–977
inflammation and reperfusion injury in, 958
intractable painful episodes in, 972
leg ulcers in, 971–972, 971f, 971t, 972t
neuropathic pain in, 959, 960t, 972
novel approaches in, 977
pain classification in, 959, 960t
pain management in, 972–978
adjuvant analgesics for, 973
approaches to, 975, 975t
day unit, 974

5828
 emergency department, 974
home-based, 973–974
hospital, 974–975
nonopioid, 973
nonpharmacologic, 973
opioid, 973
outpatient, 974
pharmacologic, 973–977
preventive therapies in, 975
WHO analgesic ladder and, 973, 973t
pain syndromes in
acute, 959–969, 960t
chronic, 960t, 969–972
classification of, 958–959
comorbid conditions and, 960t
neuropathic, 960t
secondary to therapy, 960t
pathophysiology of, 956–957, 957f
priapism in, 968–969
sickle mutation in, 955
stem cell transplant for, 977
vascular occlusion in, 822, 911, 957, 957f, 957t
vascular occlusive crisis in, 955, 959–964
abdominal, 968
acute, phases of, 961–964, 961f, 962t
established phase of, 961f, 962, 962t
initial phase of, 961f, 962, 962t
major changes in objective signs during, 962t
precipitating factors in, 961
predisposing factors in, 960–961
prevention of, 975
prodromal phase of, 961–962, 961f, 962t
relapsing or postdromal phase of, 962–964, 963f, 963t
resolving phase of, 961f, 962, 962t
treatment of, 974–975

5829
Sickle cell syndromes, 955–956, 956t. See also Sickle cell disease
Sickness, 420, 445–446
Sickness Impact Profile, 129
Side effects. See also specific drugs
of chemotherapy, 782
of childbirth pain management, 949
of local anesthetics, 1388–1389
of neuraxial analgesia, in acute pain, 834–835
of NSAIDs, 1324–1329
of opioid analgesics, 1337–1343
in cancer pain, 682–683, 696–697, 697t
in children, 798–799, 816–817, 817t
concerns, as barrier to use, 216
in intrathecal delivery, 1637
in neuraxial administration, 834–835
symptom control v., 1312
symptom control v., 1312
of tricyclic antidepressants, 386, 400, 439
Signal transduction, 26–30, 27f–29f
SIH. See Stress-induced hyperalgesia
Sildenafil, 969, 1052
“Silent” nociceptors, 24
Simple percutaneous intrathecal catheter, 712
Simple reflection, for behavioral change, 1475
Simplified measures of pain, 288–289
Simpson, James Young, 940
Sinclair, D. C., 6
Single Convention on Narcotic Drugs of 1961, 174, 206–208, 206f, 217
Single-dose neuraxial opioid analgesics, for acute pain, 833, 833t
Single-fraction radiation therapy, 768–770
Single-pulse transcranial magnetic stimulation (sTMS), for migraine,
1023, 1023t, 1024
Single-shot spinal analgesia, for childbirth pain, 947t, 949
Sinus headache, 256–257, 1134–1135
Sinusitis, 256–257, 257f, 1113

5830
Sinuvertebral nerve, 1138, 1172
Sinuvertebral nerve block (SVNB), 1268
SISAP. See Screening Instrument for Substance Abuse Potential
Site of pain
assessment of, 285–286
checklist for, 285, 289–290
in chronic low back pain, 1262
drawing of, 285, 289–290
in failed back surgery, 1293
low back, 1249–1250
Sitting, failed back surgery and, 1293
Sjögren’s syndrome, 335
Skeletal injuries, medical evaluation of, 315
Skeletal muscle
pain, 504 (See also Myofascial pain syndrome)
physiology of, 506–507
Skin, 543–565
anatomy and physiology of, 543–546
endometriosis of, 560
inflammations of, 543, 554–558
bullous dermatoses with erosions, 556–558
bullous pemphigoid, 557–558, 557f
Dercum disease (adiposis dolorosa), 554
epidermal cyst, 555–556, 555f
epidermolysis bullosa, 558
erythema nodosum, 554, 554f
hidradenitis suppurativa, 554–555, 555f
panniculitis, 554
paraneoplastic pemphigus, 557
pemphigus vulgaris, 557
Stevens-Johnson/toxic epidermal necrolysis syndrome, 556–557, 556f
neurovascular disease of, 559–560
erythromelalgia, 559
Fabry’s disease, 559–560
sensory mononeuropathies, 559

5831
 painful infections of, 543, 552–554
carbuncles, 553–554, 553f
cellulitis, 553, 553f
erysipelas, 553
erysipeloid, 554
furunculosis, 553–554
herpes simplex, 552–553, 552f
herpes zoster, 552
painful neoplasms of, 560, 560f
ANGEL mnemonic for, 560
benign, 560, 561t
malignant, 560
ulcers of, 550–551
ischemic (arterial), 550
pyoderma gangrenosum, 551–552, 551f
venous, 550–551, 551f
vascular disorders of, 546–550
antiphospholipid syndrome, 548
calcinosis cutis, 549
calciphylaxis, 549–550, 550f
cocaine levamisole toxicity, 549, 549f
warfarin (Coumadin) skin necrosis, 548–549
vasculitis of, 543, 544t–545t, 546–548
eosinophilic granulomatosis with polyangiitis, 545t, 547
granulomatosis with polyangiitis, 544t, 547
leukocytoclastic, 544t, 546, 546f
livedoid, 545t, 548, 548f
microscopic polyangiitis, 545t, 547
polyarteritis nodosa, 544t, 546–547
rheumatoid, 545t, 547–548
Skin tumors, palliative radiation therapy for, 767
Skinner, B. F., 425, 1513
Skinner box, 426
Skull base metastases, 645t
S-LANSS. See Self-Report LEEDS Assessment of Neuropathic Symptoms

5832
 and Signs
SLE. See Systemic lupus erythematosus
Sleep
abdominal pain and, 1068
assessment of, 227, 230, 238, 241, 323
chronic pain in children and, 912, 915, 920
depression and, 437
female pelvic pain and, 1085
fibromyalgia and, 437, 533–534
noncardiac chest pain and, 1047
pain and, 71
Sleep apnea
acute pain management in patients with, 841
opioid analgesics and, 1337–1338
Sleep disorders, 230
in cancer patients, 630, 632–633
cognitive-behavioral therapy for, 468–469
primary care and, 1725
screening tools for, 468
Sleep history, 227
Sleep hygiene, 1406, 1408
“Sleeping” nociceptors, 24
Slipping rib syndrome, 1189, 1198t
Small artery disease, pain associated with, 570
Small fiber neuropathy (SNF), 329, 330, 531
Small interfering RNAs (siRNAs), 757
Small intestine
autonomic stimulation of, 119t
pain, in cancer, 652
sympathetic and nociceptive nerve supply to, 116t
Small vessel vasculitis, cutaneous. See Leukocytoclastic vasculitis
SMART goals, 240, 1407, 1408
Smoking, 297, 490
Smooth muscle, opioid analgesics and, 1341
SMP. See Sympathetically maintained pain

5833
Smythe, H. A., concept of fibromyalgia, 525–526
SN. See Substantia nigra
SNAP. See Sensory nerve action potential
SNBs. See Sympathetic nerve blocks
SNCS. See Sensory nerve conduction studies
Snelson, Kenneth, 1552
SNF. See Small fiber neuropathy
Snow, John, 940
SNRIs. See Serotonin and norepinephrine reuptake inhibitors
SOAPP. See Screener and Opioid Assessment for Patients with Pain
Social factors or history, 85, 239–240
assessment of, 324
in cancer pain, 664
in low back pain, 1251
in spinal cord injury, 588
Social (observational) learning, 83, 426, 428
Social liberation, 1472t
Social proximity, in group therapy, 1464
Social reintegration, for children with chronic pain, 919–920
Social Security Administration (SSA), 302, 304–307
disability definition of, 304
evaluation methods in, 304–306, 305f
evaluation outcomes in, 306–307
Social Security Disability Insurance (SSDI), 304–308
Social support, 296
Social withdrawal, in depression, 1416
Social worker, 1713
Societal barriers, to pain relief, 155
Society for Clinical and Experimental Hypnosis (SCEH), 1421
Society of Critical Care Medicine (SCCM), 1783, 1783t
Sociobiological perspective, on emotion, 411
Sociocultural perspective
age in, 140–141
beliefs, attitudes, perceptions, and behaviors in, 141–143
complementary medicine in, 145–146

5834
 consciousness and molecular gaze in, 143–144, 147
ethnicity/race in, 139–141
influence v. construction of pain in, 138
lifeworld in, 139
medicalization of pain in, 138–139
narrative, meaning, and ethics in, 143
power, money, and systems in, 144–146
sex/gender in, 140
on transdermal pain, 137–147
Sociogenic pain, 448
Sodium amobarbital, 447
Sodium channel blockers
for central pain, 402
for neuropathic pain, 402, 1367, 1368t, 1374
Sodium channelopathies, hereditary, 332–333
Sodium channels
in local anesthetic pharmacodynamics, 1383, 1383f
in migraine, 1019–1020
in muscle physiology, 507–508
voltage-gated, 25, 30–31, 34, 50
Sodium nitroprusside, for erythromelalgia, 559
Sodium thiosulfate
for calcinosis cutis, 549
for calciphylaxis, 550
Soft corn, 1226
Soft tissue injury, neck pain with, 1233
Soft tissue tumor infiltration, 637
Soldier’s heart, 1191, 1201t
Somatic afferent system, 103
Somatic pain, 103
cancer-related, 603, 613–614, 615t, 626, 627–628
central processing of, 1066
pelvic, male, 1099, 1100t
referred low back, 1246, 1246f, 1250
visceral pain v., 103–106, 106t, 1062, 1064–1065

5835
Somatic referred pain, 1230, 1259
Somatic symptom disorders, 299, 445–448, 446t
Somatization, 299, 447–448, 525
cancer and, 629
chest pain in, 1202t
spinal surgery in patients with, 1300–1301
Somatization disorder, 446
Somatoform pain disorders, 446, 1300–1301
Somatogenic pain, 16
Somatosensory cortex, 108
in emotion and pain, 412
in nociceptive modulation, 57
opioid analgesics and, 1336
primary, 65, 66–67, 66f
secondary, 65, 66f, 67
somatotopic organization of areas, 66f
Somatosensory desensitization, 1529–1530
Somatosensory evoked potentials (SSEPs), 248
Somatostatin, 45, 46t, 49
in acute pain, 827
in cutaneous sensation, 543
intrathecal, 1627–1628
Somatostatin analogues, intrathecal, 1627–1628
SOPA. See Survey of Pain Attitudes
Soporific principle, 8
SPA. See Stimulation-produced analgesia
Spain, pain medicine in, 1755
Spasm, in complex regional pain syndrome, 345
Spasticity, 234
in spinal cord injury, 584
beneficial effects of, 589
management of, 589–590
Spatial characteristics, of pain, 289–290
measurement of, 285–286
pain drawing of, 285

5836
 pain site checklist of, 285
Special populations. See also Children; Elderly
acute pain in, 837–841
measuring pain in, 288–289, 290
Specificity coding, 1065
Specificity theory, 4, 6, 8
Sphenopalatine ganglion, 111, 112f, 113f, 725
Sphenopalatine ganglion block, 725, 1134, 1607
SPI. See Systemic phentolamine infusion
SPID. See Summed pain intensity difference
SPIKES protocol, for communication, 162–163
Spinal accessory nerve, 1146, 1153t, 1162t
Spinal anesthesia, 1385, 1736. See also Combined spinal-epidural (CSE)
analgesia; Intrathecal drug delivery
training and credentialing for, 1756–1757
Spinal chemoneurolysis, 711t, 716–717, 716f
adverse effects of, 717
contraindications to, 717
technique of, 716, 716f
Spinal column, physiologic changes in pregnancy, 944
Spinal cord
ablation, for cancer pain, 727–729
autonomic centers in, 118, 118t
cancer-related pain and syndromes of, 653–656
development of, 39
gross anatomy of, 39, 40f
metastatic compression of, 645t, 661–663, 772–776
radiation tolerance of, 774–776
Spinal cord infarction, 1765–1767
Spinal cord injury (SCI), 581–598
cardinal pain attributes in, 581, 583t
central pain after, 109–110, 398–405
mechanisms of, 399–400
neuromodulation for, 403–404
neurosurgical management of, 403–404

5837
 pharmacotherapy for, 400–403, 401t
psychological and physiotherapy treatment for, 403
extent and impact of problem, 581
as injection complication, 1765–1767, 1767f
musculoskeletal pain after, 582–584, 585f, 587f
back, 583–584
elbow and wrist, 583
management of, 588–590
nonpharmacologic treatment of, 588
pharmacologic treatment of, 589
shoulder, 582–583
spasticity-related, 584, 589–590
surgical treatment of, 589
neuropathic pain after, 110, 397, 581, 581t, 585–587, 585f
algorithm for assessing, 587f
antidepressants for, 591
antiepileptic drugs for, 590–591
at- and below-level, 585–587, 585f, 586f, 587f
cannabinoids for, 592
combined drug therapy for, 592
group therapy for, 1444t
local anesthetics for, 591
management of, 590–593
NMDA receptor antagonists for, 591–592
opioids for, 592
spinal drug administration for, 592–593
worsening, scenarios of, 585–586, 586f, 586t
neurostimulation in, 593
nociceptive pain after, 581, 581t, 582–584, 585f, 587f
algorithm for assessing, 585f, 587f
management of, 588–590
nonpharmacologic interventions in, 593–594
pain algorithms for, 585f, 586f, 587f
pain assessment and classification after, 581–588, 581t, 583t
pain management in, 588–594

5838
 pain types and etiologies after, 110, 581
psychological and environmental interventions in, 593
psychological factors in, 588
psychosocial aspects of pain after, 581, 583t, 588
red flags in, 585–586, 586t
social and environmental factors in, 588
surgical interventions in, 594
visceral pain after, 584, 585f, 587f, 590
yellow flags in, 581, 583t, 585
Spinal Cord Injury Pain Instrument (SCIPI), 396
Spinal cord stimulation (SCS), 1299, 1570–1586
affective disorders and outcomes of, 1299–1300
for angina pectoris and cardiac disease, 1191, 1575–1576, 1577f
biologic failure of, 1582
burst, 1573–1574, 1573f
for cancer pain, 725
for central pain, 404
challenges in, 1582
clinical failure of, 1582
clinical goals of, 1578
for complex regional pain syndrome, 354–355
computer modeling studies of, 1574
conventional
basic science of, 1571–1572
moderate changes of parameters, 1574
cost-effectiveness of, 1582
device options for, 1580–1581, 1580f
for elderly patients, 934
electrode for, 1580, 1580f
equipment failure in, 1582
for failed back surgery, 1573–1574, 1579
frequencies and waveforms in, 1570, 1570f, 1574
gate control theory and, 1299, 1570
for herpes zoster, 380
high-frequency, 1572–1573

5839
 history of, 1570
indications for, 1578
for ischemic pain, 1575–1576, 1575f, 1577f, 1578
for neuropathic pain, 404, 1295, 1578
neurophysiology and neurochemistry of, 1571–1572, 1572f
new waveforms in, basic science of, 1572–1574
patient management in, 1581
patient precautions in, 1581
patient selection for, 1579
for peripheral vascular disease, 1575
for phantom pain, 367
for postherpetic neuralgia, 389
potential beneficial outcomes of, 1578
prognostic factors in, 1578–1579
programming system for, 1581, 1581f
psychological failure of, 1582
psychological screening of candidates for, 1298–1309
pulse generator for, 1580–1581
screening trial of, 1579–1580
technical failure of, 1582
technical goal of, 1578
for visceral abdominal pain, 1576, 1577f, 1578
Spinal cord tethering, 587
Spinal cord-based modulatory mechanisms, 52–53
acute segmental, 52, 52f
central sensitization, 53, 54f
C-fiber wind-up, 53, 53f
heterosegmental, 53
propriospinal, 53
Spinal fusion, lumbar, 1283–1287
effectiveness of, 1283–1286, 1284t, 1285f
rationale for, 1283
Spinal hematoma, 1758–1760, 1760f. See also Epidural hematoma
Spinal infections, low back pain in, 1251
Spinal laminae, 39–42, 107

5840
 anatomy of, 39–42, 41f, 106f, 107
somatic v. visceral pain and, 104, 105f
spinothalamic neuron distribution in, 43–44, 107
visceral afferents in, 1065
Spinal manipulation, 1550
for elderly patients, 934, 935
for failed back surgery, 1294
for low back pain, 1254
Spinal nerve(s), 103, 105f
cervical, 1138, 1143–1150, 1144f, 1145f, 1146f
dermatomes of, 103, 104f, 1145, 1147f, 1150f
myotomes of, 1145, 1150f
sclerotomes of, 1145, 1150f, 1152t
Spinal nerve blocks, 1598f, 1599–1600
Spinal nociceptive processing
in acute pain, 827
defining second-order neurons in, 39
functional characterization of nociceptive neurons in, 42–43
intraspinal pathways in, 43
models of, 38
modulation of, 52–61
acute segmental, 52, 52f
biologic significance of, 64
central sensitization, 53, 54f
C-fiber wind-up, 53, 53f
CNS sites involved in, 54–55, 55t
cortical structures in, 55, 55t, 57
descending, 53–57, 56f, 108–109
heterosegmental, 53
medulla in, 54–56, 55t
neurotransmitters in, 55, 55t, 57, 60
ON, OFF, and NEUTRAL neurons in, 57–58
periaqueductal gray in, 54–56, 55t, 56f, 63–64
propriospinal, 53
spinal cord-based mechanisms of, 52–53

5841
 supraspinal, 53–58, 56f
triggers of clinical hypersensitivity in, 58–60
in neonates, 809
neuronal characterization in, 38–39
neurotransmitters in, 45–50, 46t–47t
substrates of, 38–51
targets of axonal projections in, 43–45
targets of primary afferent input in, 39–43
in visceral pain, 1065–1066
Spinal pain. See also specific causes, locations, and anatomy
axial
dorsal rhizotomy or ganglionectomy for, 1682
peripheral nerve stimulation for, 1564
peripheral neurectomy for, 1671
cancer-related, 656
compression fractures and, 259–261
diagnostic imaging in, 258–261
benign v. malignant findings in, 259–261
CT, 258–261
CT myelography, 258
discography, 261, 263f–264f
infection/inflammation in, 261, 261f, 262f
MRI, 258–261, 260f–262f
overview of, 258–259
Spinal reflexes, 118
Spinal stabilization exercise, 1540, 1541–1542
Spinal stenosis
and failed back surgery, 1290, 1291–1292, 1295
and low back pain, 1291–1292
treatment of, 1295
Spinal surgery, 1277–1278
Spinal tumors, in children, 793
Spine clinics, 1717–1721
chronic pain program in, 1719
conservative care gatekeepers in, 1718

5842
 coordination of care in, 1720
multidisciplinary approach in, 1717
occupational therapy in, 1719
pain management in, 1718
physical therapy in, 1718–1719
potential benefits of, 1719–1720
principles of, 1717
psychology in, 1718
research and education in, 1720–1721
spine surgery in, 1719
treatment components in, 1718
treatment providers in, 1718, 1718f
Spine Patient Outcomes Research Trial, 128
Spine surgery, 1298–1299
candidates for, 1298–1309
affective disorders in, 1299–1300
anger in, 1301
behavioral factors in, 1302
cognitive factors in, 1301
coping strategies in, 1302, 1303t
early-life trauma and abuse of, 1302
electronic pain assessment in, 1305
functional capacity of, 1303t, 1304–1305
medication monitoring and adverse effects in, 1303t
mood and personality of, 1303t, 1304
pain beliefs in, 1303t, 1305
pain intensity in, 1303t, 1304
pain sensitivity in, 1301
“right patient,” 1292–1293
somatization in, 1300–1301
substance abuse in, 1302
complications of, 1289
expectations in, 1288
failed (See Failed back surgery)
outcomes of, 1298–1299

5843
 psychological screening for, 1298–1309
components of, 1302–1303, 1303t
referral guidelines for, 1305–1306, 1306t
validated measures for, 1303–1305, 1303t
psychosocial risk factors in, 1306, 1306t
rates in United States, 1298
spine center for, 1719
Spinocervical tract, noxious signaling in, 414, 414f
Spinocervicothalamic tract, 45
Spinolimbic pain system, 436
Spinolimbic tract
depression–pain association in, 436, 436f
noxious signaling in, 414, 414f
Spinomesencephalic tract, 44–45
neurons of, features of, 45
noxious signaling in, 414, 414f
ventrolateral (anterolateral) pathways of, 44
Spino-olivary tract, 40f
Spinoreticular tract, 44–45, 108
neurons of, features of, 44–45
noxious signaling in, 414, 414f
ventrolateral (anterolateral) pathways of, 44
Spinothalamic tract (STT), 40f, 43–44, 65, 107–108, 108f
dorsolateral and ventromedial pathways of, 44
lesions, and central pain, 399–400
neospinothalamic, 43, 108f
neurons of
functional characterization of, 43, 107
laminar distribution of, 43–44, 107
noxious signaling in, 414, 414f
paleospinothalamic, 43, 108f
somatotopic organization of ascending fibers in, 43, 44f
ventrolateral (anterolateral) pathways of, 43
Spinous processes, 1139f, 1140, 1140f
Spirituality, 143, 802

5844
Splanchnic nerves, 111, 112f, 113, 113f, 753
Spleen, autonomic stimulation of, 119t
Splenic sequestration crisis, acute, 967–968
Splenius capitis, 1141, 1143f
Splenius cervicis, 1141, 1143f
Spondyloarthropathies, 484, 493–495
low back pain in, 1247, 1251
Spondylodiskitis, 495
Spondylolisthesis, 1247
surgery for, 1283
Spondylosis, 489
cervical, 1138, 1168–1170
low back pain in, 1247
Spontaneous activity, in EMG, 247–248, 247f, 248t
Spontaneous pain, in cancer, 644
“Spotlight” effect, 70
Spurling’s maneuver, 577, 611–612, 612f, 653, 1165
SRD. See Subnucleus reticularis dorsalis
SRFs. See Stimulus–response functions
SSA. See Social Security Administration
SSDI. See Social Security Disability Insurance
SSEPs. See Somatosensory evoked potentials
SSI. See Supplemental Security Income
SSRIs. See Selective serotonin reuptake inhibitors
Stabbing headache, primary, 1026, 1026t, 1027–1028
Stable disease, chemotherapy in, 780
Stable pain, assessment of, 281, 284f, 286
Staircase imagery, for hypnosis, 1433
Stakeholders, in rehabilitation, 1491–1492
Stalked cells, 41
Standard drink, alcoholic, 1508, 1509t
Standing, failed back surgery and, 1293
Stanford Hypnotic Clinical Scale (SHCS), 1425
Stanford Hypnotic Susceptibility Scale (SHSS), 1425
Stanford Profile Scales of Hypnotic Susceptibility, 1425

5845
Stanozolol, for livedoid vasculitis, 548
Staphylococcus aureus
and abscesses, 553
and cellulitis, 553
and epidermal cyst, 556
in HIV/AIDS, 987
methicillin-resistant, 553
and necrotizing fasciitis, 552
and venous ulcers, 551
STarT Back tool, 227, 230, 232
STAS. See State-Trait Anger Scale
State pain policy (laws), 180–185
addiction-related terminology in, 182, 183t
administrative (disciplinary) proceedings under, 193–195
criminal litigation under, 198–199
emerging trend of, 180–181
evaluating quality of, 181–182
implementing and communicating, need for, 185
improving, importance of, 185
intractable pain treatment acts, 180, 184, 194
prescription monitoring programs, 181–182, 184, 231–232, 297–298,
1518, 1747–1748
Progress Report Card on, 182–185, 184t
Washington State, 307–311, 1516–1518
State v Naramore, 198–199, 201
State-Trait Anger Expression Inventory-2 (STAXI-2), 1398–1399, 1398t
State-Trait Anger Scale (STAS), 1398
Statistical inference, Bayesian, 132
Statistical power, 129
Stavudine, neuropathy associated with, 331
STAXI-2. See State-Trait Anger Expression Inventory-2
Steindler, Arthur, 1480
Stellate ganglion, 112, 725, 1145f
Stellate ganglion block, 725, 1118, 1598f, 1600
Stem cells. See also Hematopoietic cell transplantation

5846
 intradiscal, 1274, 1650
for sickle cell disease, 977
Stenting, in cancer, 679, 679f
Stepped care, for migraine, 1024
Stepped wedge design, 132
Stereoisomers, 1382–1383
Stereotactic radiation
for nonspine metastases, 770
for vertebral metastases, 773, 776
Stereotactic radiosurgery
for thalamotomy, 1703–1704
for trigeminal neuralgia, 1116, 1691, 1695–1696
Sternoclavicular joint, 1150, 1155f, 1156f
Sternoclavicular joint arthritis, 1189, 1199t
Sternocleidomastoid muscle, 1141, 1143f
Sternum
anatomy of, 1181, 1181f
chest wall pain from disorders of, 1189–1190, 1199t
Steroids. See Corticosteroids; Glucocorticoids
Stevens-Johnson/toxic epidermal necrolysis syndrome, 556–557, 556f
Still, Andrew Taylor, 1497, 1552
Stimulation, 1526–1529. See also specific modalities
Stimulation-produced analgesia (SPA), 54, 55
Stimulator probe, for nerve conduction studies, 243–244, 244f
Stimulus control, 426, 1472t
Stimulus-induced analgesia, 64
Stimulus–response functions (SRFs), 56
sTMS. See Single-pulse transcranial magnetic stimulation
Stomach
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 116t
Stomatitis, in cancer, 754
Stone, Edmund, 8
Stone, Edward, 1315
Stool softeners, for opioid-induced bowel dysfunction, 683

5847
STOP-Bang questionnaire, 227
Straight-leg raise (SLR), 1481–1482, 1481f
Stratified care, for migraine, 1024, 1024t
Strength assessment, 1483–1484
Strength training, 1541, 1542–1543
Strengthening of Palliative Care as a Component of Comprehensive Care
Throughout the Life Course (WHA), 219–220
Streptococcus pneumoniae
in acute splenic sequestration crisis, 968
in HIV/AIDS, 987
Streptococcus pyogenes
and cellulitis, 553
and epidermal cyst, 556
and venous ulcers, 551
Stress, 418–421
and abdominal pain, 1067
and anger, 1394
and chronic pain, 420–421
ethnic differences in, 95
family, 85
immune mechanisms of, 419–420
neural substrates of, 419
and noncardiac chest pain, 1047
and pelvic pain, male, 1099, 1100
physiologic mechanisms of, 419–420
and substance abuse/addiction, 1003
Stress management
for abdominal pain, 1068
for tension-type headache, 1025
Stress response, 79, 418
Stress-induced analgesia (SIA), 59
Stress-induced hyperalgesia (SIH), 59
Stress-inoculation training, 444
Stressors, 418–419
in fibromyalgia, 527, 527t

5848
Stroke
central pain after, 398–405, 570
mechanisms of, 399–400
neuroablation for, 404
neuromodulation for, 403–404
pharmacotherapy for, 400–403, 401t
NSAIDs and, 1324–1326
pain syndromes following, 570
Strontium-89, for bone pain in cancer, 747, 765, 777–778, 777t
Structured Clinical Interview of DSM, 630, 631t
Struthers ligament, entrapment by, 1676
STT. See Spinothalamic tract
Stuart, Linda, 194
Study to Understand Prognoses, Preferences for Outcomes, and Risks of
Treatments (SUPPORT) project, 139, 152–153
Subacute sensory neuronopathy (SSN), 634, 657
Subarachnoid analgesia, 851–852
clinical, 851–852
complications of, 852–853
contraindications to, 853
opioid, 851–852
technique for, 851
Subarachnoid hemorrhage (SAH)
diagnostic imaging in, 251–256
aneurysm in, 251, 252f, 255
arterial dissection in, 251, 255f
AVM in, 251, 253f, 255
CT, 251, 252f, 253f, 254–255
CTA, 251, 253f, 255–256, 255f
MRA, 251, 254f, 255–256
MRI, 254–255
venous sinus thrombosis in, 251, 254f, 255, 255f
lumbar puncture in, 254
mortality in, 251
sudden headache in, 251

5849
Subclavian vessel compression, 575–576, 575f, 1176. See also Thoracic
outlet syndrome
Subclavius nerve, 1147
Subcostal nerve, 854
Subcutaneous opioids, 1342, 1736
for cancer pain, 698–699
Subcutaneous route, for end-of-life drug delivery, 1736
Subcutaneous tumors, palliative radiation therapy for, 767
Subgluteal approach, to sciatic nerve, 878, 879f
Subgroup analyses, 130
Subjective experience, autonomic arousal and, 413
Subjective Incompetence Scale (SI), 631t
Sublingual gland
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Sublingual opioids, 1342–1343
buprenorphine, 1008–1009
fentanyl, 693t, 694, 1735
Submandibular gland, sympathetic and nociceptive nerve supply to, 115t
Submaxillary ganglion, 111, 113f
Submucous plexus, 118, 120f
Subnucleus reticularis dorsalis (SRD), 63
Suboccipital nerve, 1145
Subphrenic abscess, 1201t
Subscapular nerve, 1153t
Subspecialty Certification in Pain Medicine, 1752
Substance abuse, 173, 187, 297–298. See also Law and policies, affecting
pain management; Substance use disorder
aberrant behavior in, 1002t, 1004–1005, 1012, 1013–1014, 1517, 1517t
assessment for, 227, 231–232, 297–298, 1508–1511, 1727
basic science of addiction in, 1002–1003, 1003f
in burn injury, 899, 905
in cancer, 601, 610, 610t, 617–618, 699–700, 700t
chronic pain treatment in patients with history of, 1001–1011
assessment tools in, 1006–1007, 1006t

5850
 balance principle and, 1001
binary concept of pain and addiction in, 1003–1004
continuum of pain and addiction in, 1004, 1004f
detoxification in, 1005
opioid agonist treatment and, 1008–1009
opioids as “gold standard” and, 1010
opioids for analgesia v. opioid-stabilizing effect in, 1005–1006
patient triage in, 1008, 1008t
separating “motive” from “behavior” in, 1004–1005
societal issues in, 1009–1010
taper in, 1005
terminating opioid therapy in, 1005–1006
universal precautions in, 1007–1008, 1007t
“worst case scenario” approach in, 1009–1010
definitions in, 1002, 1002t, 1772–1773
in emergency department, 1772–1775
ethnic differences in, 95
in failed back surgery, 1292–1293, 1295
fentanyl, 694–695
gender differences in, 93
in HIV patients, 997
pain medicine perspective on, 1516–1519
risk factors for, 700, 700t
in spine surgery candidates, 1302
Substance misuse, 1773
Substance P, 33, 41, 45–47, 46t, 49, 106–107
in abdominal pain, 1071–1072
in acute pain, 827
in bone metastases and pain, 744
in cancer pain, 733
in cutaneous sensation, 543
in fibromyalgia, 530f
in muscle physiology, 1353
in myofascial pain (trigger points), 509, 511, 512f
in opioid-induced hyperalgesia, 457–458

5851
 in pregnancy, 944
in stress, 420, 1394
in vascular occlusive crisis, 960
Substance P antagonists, intrathecal, 1629
Substance use, 296–298
prescribed and nonprescribed, 297–298
Substance use disorder, 178, 297, 453–454, 1508–1521
analgesic effects of abused drugs, 455
assessment for, 1508–1511
behavioral treatments for, 1512–1513
bridging gap between addition and pain medicine, 1519
brief interventions for, 1511
chronic illness model of, 453–454
clinical implications on pain, 454–460
clinical prevention and management of, 1518–1519
cognitive-behavioral therapy for, 469, 1512
comorbid with pain, 297
co-occurring psychiatric disorders with, 1510
and doctor–patient relationship, 478
DSM-5 criteria for, 1508, 1510, 1510t
effect on pain, 455–456
epidemiology of, 453
future directions in research, 469
genetics of pain and, 456
historical perspective on, 1516–1518
indicators of, 453, 453t
inpatient treatment for, 1512
intensive outpatient treatment for, 1512
laboratory findings in, 1509
medical history in, 1508–1509
medically supervised withdrawal for, 1511
monitoring during pain treatment, 1510–1511
need to evaluate and consider, 297
neuroanatomy of, 453, 454f
neurobiologic overlap between pain and addition in, 454

5852
 opioid hyperalgesia in, 457–460
opioid maintenance treatment for, 178, 1001, 1008–1009, 1511–1516
pain management in patients with, 453–475
for acute and perioperative pain, 462–464, 463t
for cancer or terminal pain, 464–465
in chronic nonmalignant pain, 465–466, 465t
documentation in, 466
patient and family involvement in, 466
principles of, 461–469
providing effective relief in, 461–462
reinforcing or introducing treatment in, 466
pain medicine perspective on, 1516–1519
pharmacotherapy for, 1513–1516
physical examination in, 1509
prevalence, in patients with pain, 461
primary care and, 1725
referral to addiction specialist for, 1728
in rehabilitation, managing, 1503–1504, 1504t
screening and recognition, 1508–1510
self-report questionnaires in, 1509–1510
specialty treatment for, 1511
suicide in, 466–469
tolerance in, 454, 456, 1510, 1510t
treatment and/or referral for, 1511–1516
Substance-induced psychiatric disorders, 1508
Substantia gelatinosa, 41, 107
Substantia nigra (SN), 64
Substituted judgment, of surrogate, 164
Substitution effect, 182
Success stories, 144
SUCCESS-I study, 1322
Sucralfate
for gastric protection with NSAIDs, 1327
for oral mucositis, 737, 796
SUD. See Substance use disorder

5853
Sudeck’s atrophy. See Complex regional pain syndrome
Sudomotor paralysis, 1685
Sufentanil
for acute pain
continuous epidural, 833t, 834
intravenous patient-controlled, 832t
single-dose neuraxial, 833, 833t
for childbirth pain
combined spinal-epidural, 948–949, 948t
epidural, 947t, 948, 949t
intrathecal, 714–715, 714t, 1625–1626, 1625t
trial of, 1631t
Suffering
in cancer, 602–603, 628–629
definition of, 15, 602–603
duty to relieve, 151, 152
in dying, 1738–1739
in ethics of pain management, 151–152
in Loeser’s model of pain, 85
as pain perspective, 103
in psychiatry, 448
Suggestions, in hypnosis, 1431–1434
Suicidal ideation, 433–434
antidepressants and, 918
cognitive-behavioral therapy for, 468–469
substance abuse and pain in, 467
Suicide
future directions in research, 469
opioid tapering and, 469
physician-assisted (See Physician-assisted death)
risk reduction and interventions, 468
screening for risk of, 467–468
screening tools for, 468
substance use disorder and pain in, 467–469
Suicide Assessment Five-Step Evaluation and Triage (SAFE-T), 468

5854
Sulfasalazine
for chronic proctitis, 687
for IBD-associated arthritis, 497
for psoriatic arthritis, 496
for rheumatoid arthritis, 492, 492t
Sulindac, 1316t, 1320
central nervous system effects of, 1328
hematologic effects of, 1327
for neuropathic pain, 1369
Sullivan, Mark, 141
Sullivan, Michael, 1405
Sulpiride, for tension-type headache, 1133
Sumatriptan
for children, 922
for cluster headache, 1027
for migraine, 991t, 1024t
Summary scores, in pain measurement, 274–276
Summed pain intensity difference (SPID), 15
SUNA. See Short-lasting unilateral neuralgiform headache attacks with
cranial autonomic activation
SUNCT. See Short-lasting unilateral neuralgiform headache attacks with
conjunctival injection and tearing
Superficial cervical plexus, 1146, 1146f
Superficial pain, 285
Superficial peroneal nerve, 882
Superficial phlebitis, 570
Superficial second-degree burns, 897, 898f
Superficial sensory branch of radial nerve, entrapment of, 1677
Superior cervical ganglion, 112, 113f
Superior glenohumeral ligament, 1157
Superior gluteal nerve, 1205
Superior hypogastric plexus neurolysis, 711t, 719–720, 719f, 720f
Superior mesenteric ganglion, 113f
Superior vena cava obstruction, 756
Superior vena cava syndrome, 1183–1184

5855
Supplemental Security Income (SSI), 304–308
Supportive/expressive groups, 1439, 1464
Supraacromial nerve, 1146
Supraclavicular block (SCB), 858–859
for children, 820
clinical effects of, 859
indications for, 858
landmarks for, 858
ultrasound guidance for, 858, 859f
Supraclavicular nerve, 1146, 1146f, 1151f
Supraorbital nerve stimulation, 1565
Supraorbital neuralgia, 1122–1123
Supraorbital stimulation, for migraine, 1024
Suprascapular nerve, 1147, 1148f, 1153t
Suprascapular nerve block (SSNB), 862–863, 1607
clinical effects of, 862–863
indications for, 862
landmarks for, 862
ultrasound guidance for, 862, 863f
Suprascapular nerve entrapment, 1677
Supraspinal mechanisms, of pain and nociception, 62–75
in acute pain, 827
anatomy of, 62, 62f
in neonates, 809
Supraspinal modulatory systems, 53–58, 56f
cortical structures in, 55, 55t, 57
in depression–pain association, 436, 436f
modulation of, 64
in neuropathic pain, 59
in opioid-induced hyperalgesia, 59–60
periaqueductal gray in, 54–56, 55t, 56f, 63–64
substrates mediating descending modulation, 54–57, 56f
tonic descending, 53–54, 54f
Supraspinal sources, neurotransmitters from, 49
Suprasternal nerves, 1146

5856
Suprofen, 1315
Sural nerve, 882
Surface electromyography (sEMG), 248–249
Surgical history, 229–231, 239
Surrogate decision making, 163–165
decisional capacity and, 163
identifying surrogate for, 163–164
surrogate roles and responsibilities in, 164
Survey of Pain Attitudes (SOPA), 1305
Sustainability, 77
Sustained attention, 70
Sustained-release opioids, 1342
Sutherland, William, 1553–1554
Swan-neck deformity, 491
Sweat glands, sympathetic and nociceptive nerve supply to, 115t
Sydenham, Thomas, 1–2, 2f, 8
Symonds, Sir Charles, 1028
Sympathectomy, 1668, 1682–1685
basic considerations in, 1682–1683
clinical considerations in, 1683–1684
for complex regional pain syndrome, 354, 355, 1685
indications and outcomes, 1685
operative technique of, 1684, 1684f
postoperative complications in, 1685
preoperative evaluation for, 1683
Sympathetic chain, 111, 112f
Sympathetic efferents, 1682
Sympathetic ganglia, 111–113
Sympathetic ganglion blocks, 759, 1683, 1684
Sympathetic nerve blocks (SNBs), 1600, 1601f
for complex regional pain syndrome, 354
for herpes zoster, 378–379
for obstetric pain, 940, 941, 951
for phantom pain, 364, 366
for postherpetic neuralgia, 389

5857
Sympathetic nervous system, 110, 111–114, 112f, 113f
emotion and, 412
nerve supply to body structures, 115t–117t
upper extremity supply from, 117t, 1148–1150, 1155f
Sympathetic skin response (SSR), 248
Sympathetically maintained pain (SMP), 341, 344, 354, 1682–1684
Sympathoadrenomedullary (SAM) axis, 412, 413–414, 419
Sympatholytics, 1684
Symptom Checklist 90 (SCL-90-R), 1304
Symptom clusters, in cancer, 618
Symptom control, side effects v., 1312
Symptom Distress Scale, 1734
Symptom magnification, 15, 1014
Symptom perspective, of pain, 103
Symptom Severity Index, 532, 533f
SynchroMed infusion system, 1632, 1636, 1636f
Syncope, 1763–1764
Syndrome X, 1038
Synergism, in pharmacotherapy, 1312–1313
Synovial fluid, 484, 484f
Synovial fluid analysis, 486–487, 486t
Synovial joints, 484, 484f
Synoviocytes, 484
Syringomyelia, 578, 585–586
Systematic reviews, 133
potential advantages of, 133t
quality of, assessing, 133, 133t
Systemic analgesia, for acute pain, 828–833
α-adrenergic medications in, 831
antiepileptic drugs in, 830–831
excitatory amino acids in, 830
intravenous patient-controlled analgesia in, 832–833, 832t
nonselective noradrenergic and serotoninergic medications for, 831–832
NSAIDs in, 829–830
opioid, 828–829

5858
 serotoninergic medications in, 831
steroids in, 831
Systemic lupus erythematosus (SLE), fibromyalgia with, 527
Systemic phentolamine infusion (SPI), 1683
Systems theory, 1495
Szasz, Thomas, 2

T
Tabes dorsalis, 1197t
Taboos, in cancer, 600
Tactical Combat Casualty Care, 838
Tactile allodynia, in postherpetic neuralgia, 380–381, 383
Tai chi
for elderly patients, 935
for fibromyalgia, 539
Tampa Scale of Kinesiophobia (TSK), 227, 230, 322
TAP. See Transversus abdominis plane (TAP) block
Tapentadol, 1334t, 1346
for cancer pain, 690t, 696
as centrally acting opioid agonist, 1334t, 1336
for elderly patients, 933
extended-release, 690t, 696
for fibromyalgia, 538
hepatic dysfunction and, 689t
for neuropathic pain, 1366t, 1367
for painful neuropathies, 336, 337
for postherpetic neuralgia, 387
Taper, of opioid therapy, 469, 1005, 1017, 1340
TAPS. See Tobacco, Alcohol, Prescription Medication, and Other
Substance Use (TAPS) tool
Targeted drug delivery, for central pain, 403
Targets and Reasons for Anger in Pain Sufferers (TRAPS), 1398t, 1399
Tarsal tunnel syndrome, 1220–1221, 1220f
TAT. See Thematic apperception test
Taxonomies of pain, 15–22
ACTTION-AAPM, 20, 22, 431

5859
 ACTTION-American Pain Society, 20, 21t, 22, 431
anatomy-based, 15
body system-based, 16
comprehensive, multidimensional, 18–20
duration-based, 16
empirically based, of psychological components, 18
etiology-based, 16
expert-based, 15
functioning-based, 16
IASP, 18–20, 19t, 20t, 22
inductive empirically based, 21–22
intensity- and functioning-based, 16–17
mechanism-based, 17, 17t
multiaxial, 18
prognosis-based, 17
psychometric considerations in, 22
severity-based, 16
taxonomies of, 20
TCI. See Temperament and Character Inventory
TCM. See Traditional Chinese medicine
tDC. See Transcranial direct current stimulation
Team model
in interdisciplinary chronic pain management, 1711–1713
in rehabilitation, 1493, 1494f, 1495, 1496
Technological brinkmanship, 161–162
Tectorial membrane, 1140–1141, 1142f
Tectospinal tract, 40f
Tellegen Absorption Scale, 1425
Tellington touch, 1555
Temperament, and pain, 76–77, 444
Temperament and Character Inventory (TCI), 444
TEMPO Trial, 492–493
Temporal characteristics, of pain, 11, 12f, 16, 286, 397–398, 398t
Temporal patterns, 286, 290
Temporomandibular joint (TMJ) disorders, 525, 526, 527, 1131–1132

5860
 in children, 910
diagnosis of, 1132
gender differences in, 91, 92
group therapy for, 1448t
hypnosis for, 1429
interarticular, 1131
internal derangement in, 1131–1132, 1132f, 1133t
myofascial, 1131–1132, 1132t
nociceptor sensitization in, 33
taxonomy of, 1132, 1132t
trigeminal neuralgia v., 1113
TEN. See Toxic epidermal necrolysis syndrome
Tender points, in fibromyalgia, 526–527, 534
Tenderness, 526
Tendinitis, shoulder and pectoral girdle, 1150, 1155f
Tenesmus, 1064
TENS. See Transcutaneous electrical nerve stimulation
Tensegrity model, 1552
Tensilon test, 1046
Tension-type headache (TTH), 1025, 1133–1134
in children, 910, 922–923
clinical features of, 1025
definition of, 1025, 1133
management of, 1025, 1033–1034
pathophysiology of, 1025
Terminal branch blocks, brachial plexus, 863–866
clinical effects of, 864–866
indications for, 863
nerve stimulation for, 863–864
ultrasound guidance for, 864, 864f, 865f, 866f
Terminal ganglion, 111
Test blocks, 1599
Testes, sympathetic and nociceptive nerve supply to, 117t
Testicular pain syndrome, 1098t, 1099, 1104
Testosterone, opioid analgesics and, 1338

5861
Tethering of spinal cord, 587
Tetracaine, 794, 1386t, 1626
Tetracyclines, 558, 1103
Tetrahydrocannabinol, 455, 801
Tetrodotoxin-resistant (TTX-R) receptors, in visceral pain, 752
Thalamic syndrome, 570
Thalamocingulate, 412, 412f
Thalamotomy, 1703–1704
anatomy and physiology in, 1703
indications for, 1703
outcomes of, 1704, 1704t
stereotactic open approach in, 1703
techniques of, 1703–1704
Thalamus, 62, 62f, 65, 108, 109f, 1703
central pain and, 399
in emotion and pain, 412
as gate to consciousness, 65
lateral pain system of, 65
medial, spinal connections to, 65
spinal cord injury and, 110
Thalassemias, 955–956, 956t
The Joint Commission, 826
Thematic apperception test (TAT), 1398
Theophylline
for low CSF volume headache, 1030
for noncardiac chest pain, 1052, 1053–1054, 1054f
Therapeutic massage. See Massage therapy
Therapeutic nerve blocks, 1607–1608. See also specific nerve blocks
Therapeutic relationship, in rehabilitation, 1496
Therapeutic touch, 1554–1555
Therapeutics (clinical pharmacology), 1311
Thermal evaluation, 235
Thermal hyperalgesia, neuropathy and, 330
Thermal neurotomy, 1653
Thermal radiofrequency intradiscal therapies, 1646–1648

5862
Thermal radiofrequency neurotomy, 1653, 1655–1664
for ankylosing spondylitis, 1188
applications of, 1656–1664
for brainstem procedures, 1657
for central ablative procedures, 1656–1657
cervical medial branch, 1171, 1230–1239, 1239f, 1660–1662, 1661f
for cordotomy, 1657
for discogenic pain, 1295
for dorsal root entry zone lesions, 1657
efficacy of, 1555t
for intercostal neuralgia, 1186
lumbar medial branch, 1275–1276, 1275f, 1278–1279, 1657–1660,
1659f
occipital, 1239–1240, 1240f, 1662–1663, 1663f
pathology of, 1656
physics of, 1654–1655, 1655f, 1656f
physiology of, 1656
for sacral lateral branch, 1663–1664
for thoracic facet syndrome, 1188
for trigeminal neuralgia, 1115–1116, 1656
Thermal sensitivity, of nociceptors, 24
Thermocoagulation, percutaneous RF intradiscal, 1647–1648
Thermotherapy, 1522–1523. See also Heat therapy
Thiamine deficiency, 332
“Thigh splints,” 1215
Thiopental, for palliative sedation, 1739t
Third occipital neurotomy, 1239–1240, 1240f, 1662–1663, 1663f
Third-party payers, skepticism about pain, 76
Third-wave therapies, 1405, 1410
Thompson, Kay, 1429, 1435
Thoracic aorta, diseases of, 1193t–1194t
Thoracic aortic aneurysm, 572, 1193t–1194t
Thoracic disk herniation, 1184, 1185f
Thoracic epidural analgesia (TEA), 850, 850t
Thoracic facet syndrome, 1188, 1198t

5863
Thoracic ganglia, 1145
Thoracic inlet syndrome, 1201t
Thoracic neurolysis, 717
Thoracic outlet
anatomy and physiology of, 575–576, 575f
compression of, 575, 1176, 1677
Thoracic outlet syndrome (TOS), 264, 267, 575–580, 1138, 1176–1177
arterial, 267, 576, 1176
botulinum toxin for, 578, 579
clinical presentation of, 576–577, 576t, 1176
diagnostic imaging in, 267, 577–578, 577f, 578f, 1176
diagnostic tests in, 577–578
differential diagnosis of, 578
electrodiagnostic tests in, 578
management of, 578–579, 1176
neurogenic, 267, 576–577, 576t, 1176
nonspecific, 1176
outcomes of, 579
physiotherapy for, 579, 1176
provocative tests in, 576–577
surgical decompression for, 579, 1677
treatment goals in, 578–579
venous, 267, 576, 1176
Thoracic pain. See also Chest pain; Chest wall pain
biomechanical considerations in, 1485–1486
dorsal rhizotomy or ganglionectomy for, 1680
Thoracic paravertebral block, 866–868, 867f, 888t
Thoracic spine
anatomy of, 1180, 1181f, 1182f
chest wall pain from disorders of, 1184–1188, 1197t–1198t
Thoracic sympathetic ganglion block, 759
Thoracic viscera, sympathetic and nociceptive nerve supply to, 115t
Thoracic wall blocks, 885–886
Thoracodorsal nerve, 1153t
Thoracolumbar division. See Sympathetic nervous system

5864
Thoracotomy, pain after, 658, 1191, 1200t
Thorndike, Edward, 425
Thromboangiitis obliterans, 570, 571f
Thrombocytopenia, neuraxial techniques contraindicated in, 853
Thrombolysis, for thoracic outlet syndrome, 579
Thrombosis. See also Deep venous thrombosis
cancer-related, 756
Thunderclap headache, 251, 1029
Thyroid cancer, low back pain in, 1251
Thyroid cartilage, 1139f, 1163
Thyroid function tests, 1168
Thyroid gland
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 115t
Thyrotropin-releasing hormone stimulation test, 435
Tiagabine, for neuropathic pain, 1366
Tibial nerve, 1205, 1215–1216
Tibial nerve entrapment, 1678
Tibial tendon insufficiency, posterior, 1221
Tic convulsif, 1112
Tic douloureux. See Trigeminal neuralgia
Tietze syndrome, 1189, 1198t
Time, for pain evaluation, 227
Time constraints, in primary care, 1724
Time dimension, of pain, 11, 12f, 16, 286, 290
Timing of pain (T), 228–229, 228f, 664
Timolol, for migraine, 990t
Tinel sign, 249, 576, 1175, 1669, 1673
Tinnitus, NSAIDs and, 1328
Tissue plasminogen activator, for livedoid vasculitis, 548
Titin, 506, 507f
Tizanidine, 1352t, 1354, 1355
as adjuvant analgesic, 685
for fibromyalgia, 538
intrathecal, 1626, 1627

5865
 for migraine, 991t
for spinal cord injury, 589
TMJ. See Temporomandibular joint (TMJ) disorders
TMS. See Transcranial magnetic stimulation
TNF. See Tumor necrosis factor
TNS. See Total Neuropathy Scale
Tobacco, Alcohol, Prescription Medication, and Other Substance Use
(TAPS) tool, 1510
Tobramycin lozenges, 738
Tocilizumab, for rheumatoid arthritis, 492t, 493
Tofacitinib, for rheumatoid arthritis, 492t, 493
Tolerance, drug, 15
definition of, 840, 1002t, 1772–1773
opioid, 690–691, 1338–1340, 1772–1773
acute pain management in, 840–841
to analgesia, 1338
associative, 1339
in burn injury, 899
in children, 799
clinically observable, 1338–1339
to CNS-depressing effects and nausea, 1338–1339
hyperalgesia and, 457
in intrathecal drug delivery, 1637–1638
in opioid use disorder, 456, 1510, 1510t
to opioid-induced constipation, 1338–1339
opioid-sparing strategies to reduce, 1339–1340
pharmacologic, 1339
presurgical prehabilitation program in, 841
proposed mechanisms of, 1339–1340
in science of addiction, 1003
in substance use disorder, 454, 456, 1510, 1510t
Tolerance, TENS, 1527
Tolerance level, pain, 14
ethnicity/race and, 95, 139
gender differences in, 92, 841–842

5866
Tolfenamic acid, for migraine, 1024, 1024t
Tolmetin, 1316t, 1320, 1328
Tolosa-Hunt syndrome, 1113
Tomlinson, Lester, 195, 197–198
Tomlinson v Bayberry Care Center, et al., 197–198
Tonic descending modulation, 53–54, 54f
Tonsillectomy, NSAIDs for children after, 811
Tooth, anatomy of, 1130, 1130f
Tooth pain, 1130–1131
diagnosis of, 1130, 1131t
trigeminal neuralgia v., 1113
TOPAR. See Total pain relief
Tophaceous gout, 499, 499f
Tophi, 499
Topical agents
as adjuvant analgesics, 685
analgesic balms, 1356–1357, 1356t
for burn pain, 902
for cancer pain, 685
for cancer pain in children, 794
for children, 817
for complex regional pain syndrome, 353
counterirritants, 1356–1357
for elderly patients, 932, 933–934
for end-of-life pain, 1736
for local anesthesia, 1386
for neuropathic pain, 1369, 1370t
NSAIDs, 1318, 1319t, 1356–1357
for oral mucositis, 737–738
for painful neuropathies, 337–338
for postherpetic neuralgia, 385t, 387–388, 1186
for rib fracture pain, 1189
for sympathetically maintained pain, 1684
ultrasound and absorption of, 1526
Topiramate

5867
 for cluster headache, 1134
for failed back surgery, 1295
for hemicrania continua, 1029
for migraine, 990t
for migraine prevention, 1023t
for neuropathic pain, 1365–1366, 1365t
for painful neuropathies, 337
for paroxysmal hemicrania, 1027
for phantom pain, 365
for raised CSF pressure headache, 1031
for spinal cord injury pain, 591
for trigeminal neuralgia, 1114–1115
Topographic remapping, in phantom pain, 364
TOPS. See Treatment Outcomes of Pain System
Torts, 193, 195–198
TOS. See Thoracic outlet syndrome
Total disk arthroplasty, 1291
Total Neuropathy Scale (TNS), 796
Total pain, 7
Total pain relief (TOPAR), 15
Touch
assessment of, 398
healing, 1554, 1555
therapeutic, 1554–1555
Toxic epidermal necrolysis syndrome, 556–557, 556f
Toxic neuronopathy, 335
Toxic neuropathies, 329–330, 331, 988t
Toxoplasmosis, in HIV/AIDS, 989
Trachea, palliative radiation therapy for, 766
Tracheobronchitis, acute, 1194t
Tracking and monitoring, of prescriptions, 181–182, 184, 187, 231–232,
297–298, 1518
Traction, for low back pain, 1271
Tracts, of spinal cord, 39, 43–45
Traditional Chinese medicine (TCM), 1552, 1553

5868
Training
interventional pain medicine, 1755–1756, 1757t
pain specialist, 1751–1757
Tramadol, 1334t, 1346
for acute pain, 829
for cancer pain, 696
for cancer pain in children, 799
for central pain, 401t, 402, 402f
as centrally acting opioid agonist, 1334t, 1336
for children, 813
dose conversions of, 829t
for elderly patients, 933
for failed back surgery, 1295
for fibromyalgia, 538
hepatic dysfunction and, 689t
for herpes zoster, 378, 379t
for HIV pain, 994t
interaction with antiretroviral therapy, 995t
for male pelvic pain, functional effects of, 1103t
for neuropathic pain, 402, 686t, 1366t, 1367
for painful neuropathies, 336, 337
perineural, 853–854
for phantom pain, 365
for postherpetic neuralgia, 385t, 387, 1118
relative efficacy of, 829, 829t
for spinal cord injury pain, 589, 592
Tramadol/acetaminophen, in emergency department, 1775–1776
Trance, 1422–1423, 1432, 1433–1434. See also Hypnosis
Transactional stress model, 77–78
Transcranial direct current stimulation (tDC), 57
of dorsolateral prefrontal cortex, 70
for fibromyalgia, 538
for spinal cord injury, 593
Transcranial magnetic stimulation (TMS), 57
in complex regional pain syndrome, 345

5869
 repetitive, 1587, 1591–1592
basic considerations in, 1591–1592
efficacy of, 1592
for fibromyalgia, 538
for phantom pain, 367
procedure for, 1591, 1591f
single-pulse, for migraine, 1023, 1023t, 1024
Transcutaneous electrical nerve stimulation (TENS), 1526–1527, 1558
burst, 1527, 1573
for childbirth pain, 946
for dysmenorrhea, 1084
for elderly patients, 934
for fibromyalgia, 538
interferential current v., 1528
for lateral femoral cutaneous nerve entrapment, 1211
for low back pain, 1272
for noncardiac chest pain, 1040
over-the-counter units for, 1527
pathophysiology and mechanisms of, 1558–1559
for phantom pain, 367
for postherpetic neuralgia, 390, 1186
for sickle cell disease pain, 973
for spinal cord injury, 590, 593
for tarsal tunnel syndrome, 1221
tolerance to, 1527
Transcutaneous electrical stimulator probe, 243–244, 244f
Transdermal fentanyl, 828, 1345
for acute pain, 828
for cancer pain, 690, 690t, 693–694
for cancer pain in children, 798
for children, 815
clinical parameters of, 693t
for end-of-life pain, 1736
formulations of, 693
for HIV pain, 994t

5870
 for opioid-tolerant patients, 840
overdose of, 694–695
pharmacokinetics of, 690, 690t, 693–694, 693t
for postherpetic neuralgia, 385t
Transdermal opioids, 1342, 1736
Transdermal pain
defining, 138–139
sociocultural perspective on, 137–147
Transdermal process, pain as, 448
Transdermal route, for end-of-life drug delivery, 1736
Transforaminal diagnostic injections, 1794
Transforaminal epidural steroid injections, 1611, 1615–1620
adverse events in, 1619–1620
alternative needle placements in, 1615, 1616f
for chronic back pain, 1274
CT guidance for, 1620
determinants of efficacy, 1619
evidence on, 1618–1619, 1620
for failed back surgery, 1289
fluoroscopic guidance for, 1615, 1616f, 1617f, 1618–1619
for radicular pain, 1620
technique of, 1615–1618, 1616f, 1617f
Transforming growth factor (TGF), in cancer pain, 627
Transient pain, 12
Transient receptor potential (TRP), 26, 106, 628, 745, 752
Transmitters. See Neurotransmitters
Transmucosal fentanyl, 693t, 694, 838
for cancer pain in children, 798
dose conversions for, 695t
for end-of-life pain, 1735
risk evaluation and mitigation strategy for, 694
Transmucosal opioids, 901–902, 1342
Transmucosal route, for end-of-life drug delivery, 1735
Transtheoretical model, of behavior change, 1471–1472, 1491
Transthyretin, in amyloid neuropathy, 333

5871
Transverse lesion syndrome, 1170t
Transverse ligament, 1141, 1142f
Transverse processes, 1140, 1140f
Transversus abdominis plane (TAP) block, 854–856
for children, 821
landmark technique for, 854, 855f
posterior extension of, 883–885
ultrasound-guided, 855–856, 855f
Tranylcypromine, 438
Trapezoid ligament, 1150–1156
Trapped ovary syndrome, 1088
Travell, Janet, 504
Trazodone
for children, 917
for noncardiac chest pain, 1052, 1053
for spinal cord injury pain, 591
Treatment. See Pain management; specific drugs and treatments
Treatment as usual, group therapy v., 1442–1456
Treatment of Pulmonary Hypertension and Sickle Cell Disease with
Sildenafil Treatment (Walk-PHaSST) trial, 969
Treatment Outcomes of Pain System (TOPS), 1305
Treatment series, 123–124
Tremors, in complex regional pain syndrome, 345
Triage
of chronic pain patient, 1008, 1008t
in low back pain, 1247–1253, 1248f
Trial of therapy, 1007–1008, 1013
Triamcinolone, epidural injections of, 1611
Tricyclic antidepressant(s)
for abdominal pain, 1070
for acute pain, 831–832
for anesthesia dolorosa, 1123
for anxiety, 441, 442
for central pain, 400–402, 402f
for chemotherapy-induced peripheral neuropathy, 686

5872
 for children, 917
for depression, 438–439, 1416–1417
for elderly patients, 933
for fibromyalgia, 535, 536t
for herpes zoster, 378, 379t
for HIV pain, 994t, 995–996
for intercostal neuralgia, 1186
intrathecal, 1628
for low back pain, 1271
for male pelvic pain, 1105
for migraine, 990t, 1133
for migraine prevention, 1023t
for neuropathic pain, 400–402, 686t, 1359–1361, 1360t, 1361t
for noncardiac chest pain, 1052–1053
for nummular headache, 1123
for painful neuropathies, 336
for phantom pain, 365
for postherpetic neuralgia, 384t, 386, 1118, 1186
for posttraumatic headache, 1031
for posttraumatic stress disorder, 444
side effects of, 386, 400, 439
for spinal cord injury pain, 591
for tension-type headache, 1025
Tricyclic antidepressant-like muscle relaxants, 1352t, 1354–1355
Trigeminal autonomic cephalgias, 1112
Trigeminal nerve, 723, 723f, 1162t, 1691
Trigeminal nerve block, for cancer pain, 723–725
adverse effects of, 723
general considerations in, 723
indications for, 723
outcome studies of, 725
techniques of, 723–725, 724f
Trigeminal nerve reflexes, 246
Trigeminal nerve stimulation, 1565
Trigeminal neuralgia (classical), 258, 1108, 1109–1117, 1128–1129, 1129t

5873
anatomy in, 1109f
cancer-related, 653
deafferentation, 13, 1123, 1129
diagnostic imaging in, 258, 259f
differential diagnosis of, 1112–1113
epidemiology of, 1110, 1691
etiology and pathophysiology of, 1110–1111, 1128–1129
glycerol injection for, 1653
historical perspective on, 1109–1110
ICHD-III criteria for, 1111–1112, 1111t, 1691, 1691t
idiopathic, 1128
medical management of, 1113–1115, 1691, 1692
microvascular decompression for, 1110, 1115–1116, 1691–1694, 1693f,
1694f
nerve and neurolytic blockade for, 1115, 1653, 1654, 1656
painful trigeminal neuralgia v., 1108, 1112, 1117, 1128, 1691
pathophysiology of, 1691–1692
patient presentation, 1691
percutaneous balloon compression for, 1695
percutaneous rhizotomy for, 1691, 1694–1695, 1695f
peripheral nerve stimulation for, 1566
peripheral neurectomy for, 1116–1117
peripheral v. central mechanism in, 1110–1111
postherpetic, 1129
rare presentations of, 1112, 1122–1123
short-lasting headache in, 1026, 1026t
stereotactic radiosurgery for, 1116, 1691, 1695–1696
surgical management of, 1115–1117, 1691–1697
algorithm for, 1692, 1692f
evaluation for, 1692, 1692f
palliative ablative v. nondestructive, 1692
symptomatic, 1128–1129
symptoms and signs of, 1111–1112, 1691
trigger zones in, 1111–1112, 1112f
vascular compression theory of, 1110

5874
Trigeminal neuropathy, 1108, 1128–1129, 1129t. See also Painful
trigeminal neuropathy; Trigeminal neuralgia (classical)
Trigeminal radiofrequency rhizotomy, 1115–1116
Trigeminal-autonomic cephalalgias, 1025–1027, 1025t. See also Cluster
headache
Trigeminothalamic tract ablation, 1704–1705
Trigeminovascular system, 1019
Trigger point(s)
active, 506
basic concepts of, 504–506
biochemical milieu of, 511–513
in cancer, 613, 627–628
catecholamines and ANS in, 511–512
central sensitization and, 509–511
Cinderella hypothesis of, 508
clinical management of, 513–518
cytokines in, 512–513
definition of, 506
diagnosis of, 513–514
energy crisis hypothesis of, 504
historical perspective on, 504
integrated, hypothesis of, 504–506, 510–511
introduction of term, 504
latent, 506
magnetic resonance imaging of, 515
motor endplates and, 507–508
muscle nociceptor activation and, 508–509
muscle physiology and, 506–508
needling therapies for, 515–517
neuropeptides and inflammatory mediators in, 511, 512f
palpation of, 506, 506f, 513–515, 514f
patient education on, 515
in pelvic pain, 1089, 1100–1102, 1104
peripheral sensitization and, 508–509
pH and, 511

5875
 physical examination of, 513–514
referred pain patterns, 505f, 514
shockwave emitters for, 515
treatment of, 515–518
invasive, 515–517
noninvasive, 517–518
ultrasound of, 515
Trigger point injections
for cancer pain, 613
for fibromyalgia, 539
for low back pain, 1272
for male pelvic pain, 1104
for myofascial pain, 515–517, 517f
Trigger point manipulation, 1552
Trigger Point Manuals (Travell and Simons), 504
Trigger zones, in trigeminal neuralgia, 1111–1112, 1112f
Trimethoprim-sulfamethoxazole, 553, 556
Triple imbedded metaphor technique, 1435
Triptans
for children, 922
for cluster headache, 1027, 1134
combined with NSAIDs, 1024
for migraine, 990t–991t, 1023–1024, 1024t, 1133
for primary exertional headache, 1028
for primary sex headache, 1028
for tension-type headache, 1025
TrkA, 106
Trochanteric pain syndrome, 1289–1290, 1289t
Trochlear nerve, 1162t
Trophic abnormalities, 233, 233f, 344–345
Tropisetron, for trigger point injections, 516
Tropomodulin, 506–507, 507f
Tropomyosin, 506–507
Troponin, 506–507, 507f
Truncal pain. See also Back pain; Low back pain

5876
 peripheral nerve stimulation for, 1564–1565
postsurgical, dorsal rhizotomy or ganglionectomy for, 1680
Trunk, sympathetic and nociceptive nerve supply to, 117t
Trust, 1744–1745, 1748–1749
Tseng, Hsiu-Ying “Lisa,” 199
TSK. See Tampa Scale of Kinesiophobia
TTH. See Tension-type headache
T-tubules, 506, 507
Tuberculosis
HIV-related, 986
isoniazid and pyridoxine deficiency in, 331–332
Tufts Program on Pain Research, Education and Policy, 173
Tumor(s)
chest wall pain with, 1182–1184
infiltration and inflammation of serous mucosa, 638
infiltration of abdominal hollow organs, 637–638
infiltration of bone, 637
infiltration of peripheral nerves, 637
infiltration of sacrum and sacral nerves, 656
infiltration of soft tissues, 637
infiltration of viscera, 651, 652t
involvement of encapsulated organs, 637
pain syndromes due to, 645t–646t
pain with, 625–627, 637–644 (See also Cancer pain)
CNS mechanisms of, 626
molecular mechanisms of, 627
PNS mechanisms of, 626–627
tumor type and disease stage in, 638–644
skin, painful, 560, 560f, 561t
Tumor ablation, image-guided, 711t
Tumor markers, 643, 644t
Tumor necrosis factor (TNF), 485, 627, 732
Tumor necrosis factor alpha (TNF-α), 32, 49
in cancer pain, 628, 732
in complex regional pain syndrome, 342

5877
 in myofascial pain (trigger points), 512–513
in opioid-induced hyperalgesia, 458
in sickness response, 420
in stress, 420
Tumor necrosis factor beta (TNF-β), 745
Tumor necrosis factor (TNF) inhibitors
for ankylosing spondylitis, 494
for calcinosis cutis, 549
for IBD-associated arthritis, 497
for reactive arthritis, 496
for rheumatoid arthritis, 492–493, 492t
Tumor-induced algesia, in head and neck cancer, 732
Tumor-related gynecomastia, 755
Tunneled intrathecal catheter, 712
12-step facilitation therapy, 1513
Twilight sleep, during childbirth, 940
Twin studies, 96
Two-needle, two interspace techniques, 852
Typical angina, 1041–1042
Tyrosine kinases, 49–50

U
Ubrogepant, for migraine, 1024
UDT. See Urine drug testing
UGRA. See Ultrasound-guided regional anesthesia
Ulcer(s)
anorectal, in HIV/AIDS, 986
cutaneous, 550–551
ischemic (arterial), 550, 569–570
leg, in sickle cell disease, 971–972, 971f, 971t, 972t
NSAID-induced, 1327
peptic, 1201t
perforated, 1201t
pyoderma gangrenosum, 551–552, 551f
venous, 550–551, 551f
Ulcerative colitis, arthritis associated with, 496–497

5878
Ulnar nerve
anatomy of, 1147, 1148f, 1149f, 1151f, 1154t
evaluation of, 1482, 1483f
nerve conduction studies of, 244–245, 245f, 246f
Ulnar nerve block, 863–866, 864f, 865f, 866f
Ulnar nerve entrapment, 264, 266f, 267, 1676
Ulnar nerve entrapment at elbow (UNEE), 1676
Ulnar nerve entrapment at wrist, 1676
Ulnar neuropathy
electrodiagnostic tests in, 249
magnetic resonance neurography of, 264, 266f
Ultimate user level, opioid diversion at, 187
Ultrarapid opioid withdrawal, 1511
Ultra-short-acting opioids, 1342
Ultrasound, 251
in adenomyosis, 1087
in interdigital neuroma, 1224
in lumbosacral plexopathy, 1205
in metatarsalgia, 1222
in myofascial pain (trigger points), 515
in neck and arm pain, 1168
in nerve block guidance, 1598–1599, 1598f
in nerve entrapment, 267, 1673, 1674f
in noncardiac chest pain, 1037–1038, 1048
in peripheral nerve device implantation, 1561–1563, 1561f, 1562f
in peripheral nerve stimulation, 1559
in thoracic outlet syndrome, 1176
in uterine retroversion, 1082
Ultrasound guidance
in adductor canal block, 873, 874f
in ankle block, 882–883, 883f
in axillary block, 861, 862, 862f, 864f
in fascia iliaca block, 875, 875f
in femoral nerve block, 871–872, 871f, 872f
in ilioinguinal block, 856f

5879
 in infraclavicular block, 860, 860f
in interscalene block, 857–858, 857f, 858f
in lateral femoral cutaneous nerve block, 876, 876f
in lumbar plexus block, 870, 870f
in obturator nerve block, 877, 877f
in PECS/serratus anterior plane block, 886, 886f
in quadratus lumborum block, 885, 885f
in rectus sheath block, 856
in sacral plexus-sciatic nerve block, 878–879, 880f, 881f
in supraclavicular block, 858, 859f
in suprascapular nerve block, 862, 863f
in terminal branch blocks, 864, 864f, 865f, 866f
in transversus abdominis plane block, 855–856, 855f
Ultrasound therapy, 1525–1526
contraindications to, 1526
indications for, 1526
for myofascial pain, 518, 1526
thermal and nonthermal effects of, 1525–1526
Ultrasound-guided regional anesthesia (UGRA), 857
Unbearable sensations, in disability, 302
Unconditioned reflexes, 425
Unconscious, 1422
Uncontrolled studies paradigm, 123–124
Undertreatment of pain, 139, 1311
in cancer, 623, 676, 676t
pediatric, 789–790
in elderly, 929–930
ethical issues in, 151, 152–156
ethnicity/race and, 139–140
in HIV/AIDS, 997
identifying barriers to pain relief, 153–155
Unexplained pain syndromes, 525. See also Fibromyalgia
Unintended destinations, of local anesthetics, 1763
Union for International Cancer Control, 220
United Kingdom, pain medicine in, 1755

5880
United Kingdom Back Pain Exercise and Manipulation trial, 131
United Nations. See also specific organizations and programs
on opioid analgesics, 205
efforts to improve availability and access, 220–221
recommendations, 219–220
United Nations Commission on Narcotic Drugs, 174
United Nations Economic and Social Council, 174
United Nations Office on Drugs and Crime (UNODC), 219
United States
NSAIDs available in, 1316t
topical NSAIDs in, 1319t
United States v Hurwitz, 200–201
United States v McIver, 201
United States v Rosen, 199–200
Universal precautions, in pain medicine, 617–618, 1007–1008, 1007t
“Universal” receptors/channels, 50
Unorthodox medical practice, 1546–1547
Unprotected sexual intercourse (UPSI), 1079
Unrelieved pain, as public health problem, 172
Upper crossed syndrome, 1486
Upper endoscopy, for noncardiac chest pain, 1042–1043, 1042t
Upper extremities
nerve entrapment syndromes of, 1138, 1173–1174, 1174t
nerve supply to muscles of, 1153t–1154t
neural tension tests in, 1482, 1482f, 1483f
nociceptive nerve supply to, 117t
peripheral nerve injuries of, 1163t
peripheral nerve supply of, 1151f
segmental nerve supply of, 1150f
sympathetic supply to, 117t, 1148–1150, 1155f
Upper extremity nerve block, 857–866
axillary, 861–862, 862f, 864f
brachial plexus terminal branch, 863–866
infraclavicular, 820, 859–861, 860f, 861f
interscalene, 857–858, 857f, 858f

5881
 local anesthetic dosing in, 888t
supraclavicular, 820, 858–859, 859f
suprascapular, 862–863, 863f, 1607
Upper extremity pain. See also Arm pain; Shoulder pain
group therapy for, 1439
nerve blocks for, 1607
after spinal cord injury, 583
Upper motor neuron dysfunction, 234t
Upper trunk, of brachial plexus, 1147
Urate gout, 497–500, 1224
Ureteral obstruction, 755
Ureteral spasm, adjuvant analgesics for, 687
Ureters
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Urethral syndrome, 1088, 1089
Urethritis, low back pain in, 1251
URGES questionnaire, 227
Urinary bladder
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Urinary bladder cancer
intravesical chemotherapy for, 755–756
palliative radiation therapy for, 767
Urinary retention
opioid-induced
in children, 798–799
in intrathecal therapy, 1637
uterine retroversion and, 1082
Urine drug testing (UDT), 157, 1012, 1014–1017, 1509
detection times in, 1015t, 1016, 1509, 1509t
frequency of, 1015
future considerations in, 1017
limitations of interpretation, 1016
opioid, 1016, 1016f

5882
 patient candidates for, 1015
for patients with history of substance abuse, 1004, 1005
presumptive v. definitive, 1015–1016
purpose of, 1014
retention times and detection windows in, 1015t, 1016
specimen choice for, 1014–1015
strategies for, 1015
“two-step” presumptive approach in, 1017
unexpected results in, dealing with, 1016–1017
in universal precautions, 1007
Urocortins, 46t, 49
Urogenital pain syndromes, male, 1098, 1098t. See also Pelvic pain, male
U.S. federal law
criminal prosecution under, 199–201
drug control and medical use under, 175–180
U.S. Supreme Court cases, over pain management, 201–202
Ustekinumab, for psoriatic arthritis, 496
Usui, Mikao, 1555
Uterine cervical pain, in cancer, 653
Uterine fibroids (leiomyomas), 1082
Uterine fundus pain, in cancer, 653
Uterine retroversion, 1082, 1082f
Uteroplacental unit, 945
Uterus
autonomic stimulation of, 119t
sympathetic and nociceptive nerve supply to, 117t
Utility, of pain measurement, 273

V
Vacco v Quill, 201–202
Vagal afferents, 45
abdominal, 1065, 1065f
esophageal, 1046, 1046f
Vagal neuralgia, 1120–1122
anatomy in, 1120–1121, 1121f, 1122f
diagnosis of, 1121–1122

5883
 etiology of, 1121
symptoms and signs of, 1121
treatment of, 1122
Vaginal administration, of opioids, 1343
Vaginismus, 1090–1091, 1091f, 1092
Vagus nerve, 111, 112f, 1120–1121, 1121f, 1122f, 1162t
Vagus nerve stimulation
for cluster headache prevention, 1027
for hemicrania continua, 1029
for migraine, 1024, 1024t
for paroxysmal hemicrania, 1027
Valacyclovir, 377, 377t, 552–553
Valdecoxib, 811, 1318, 1323, 1324
Valence, in emotion, 411
Validation, of patient experience, 1726–1727
Validity, 22, 272–273
Valproate/valproic acid
for central pain, 401t
for children, 812
for migraine, 990t
for migraine prevention, 1023t
for neuropathic pain, 1364t–1365t, 1365
for spinal cord injury pain, 590–591
for trigeminal neuralgia, 1114
Valsalva test, 1165
Valsalva’s maneuver-related headache, 1028
Value judgments, avoiding, 1474
Values, 143
core, of health care, 151–152
in end-of-life care
patient, 161
physician, 161–162
Vancomycin, for infectious arthritis, 501
Vanderbilt Pain Management Inventory (PMI), 1302
Vane, John, 1317

5884
Variable pain (variability), 281, 284f, 286
Varicella vaccination, 380, 390, 391, 1118
Varicella-zoster immunoglobulin (VariZIG), 380
Varicella-zoster virus (VZV), 372. See also Postherpetic neuralgia
VAS. See Visual Analog Scale
Vascular disorders
cutaneous, 546–550
pain in, 566–574
neuroanatomy and neurophysiology of, 566
nonvascular pain v., 571–572
relief of, 572–573
Vascular endothelial growth factor (VEGF), 50, 627
Vascular headache, 1019
Vascular loop compression, 258, 259f, 260f
Vascular obstruction, cancer-related, 756
Vascular occlusion, in sickle cell disease, 822, 911, 957, 957f, 957t
Vascular occlusive crisis (VOC), 955, 959–964
abdominal, 968
acute, phases of, 961–964, 961f, 962t
established phase of, 961f, 962, 962t
initial phase of, 961f, 962, 962t
major changes in objective signs during, 962t
precipitating factors in, 961
predisposing factors in, 960–961
prevention of, 956
prodromal phase of, 961–962, 961f, 962t
relapsing or postdromal phase of, 962–964, 963f, 963t
resolving phase of, 961f, 962, 962t
treatment of, 974–975
Vascular pain syndromes, 567–571
aortic and large artery, 569
intermittent claudication, 567–569, 567f
poststroke, 570
rest pain, ulcers, and gangrene, 569–570
small artery disease-associated, 570

5885
 venous, 570
Vascular syndrome, myelopathic, 1170t
Vascular thoracic outlet syndrome, 267, 576, 1176
Vasculitic neuropathy, 334
Vasculitis
ANCA, 547
cutaneous, 546–548
eosinophilic granulomatosis with polyangiitis, 545t, 547
granulomatosis with polyangiitis, 544t, 547
leukocytoclastic, 544t, 546, 546f
livedoid, 545t, 548, 548f
microscopic polyangiitis, 545t, 547
polyarteritis nodosa, 544t, 546–547
rheumatoid, 545t, 547–548
imaging in, 256, 256f
large- and medium-artery, 569
paraneoplastic, 634, 657
rheumatoid, 493, 545t, 547–548
Vasectomy, pain syndrome after, 1098t
Vasoactive intestinal peptide (VIP), 46t, 48, 107, 543, 827
Vasoconstriction, local anesthetics and, 1387
Vasodilators, for acute chest syndrome, 966
Vasoregulatory asthenia, 1191
Vasovagal reactions, 1763–1764
VEGF. See Vascular endothelial growth factor
Veins
disorders of, pain associated with, 570
innervation of, 566
pain management for, 573
Velafermin, for oral mucositis prevention, 738
Vena cava compression, in pregnancy, 943–944, 944f
Venlafaxine
for acute pain, 832
for central pain, 402
for chemotherapy-induced peripheral neuropathy, 686

5886
 for depression, 436, 438–439
for elderly patients, 933
for fibromyalgia, 537
for HIV pain, 994t, 995–996
for male pelvic pain, 1105
for migraine, 990t
for neuropathic pain, 402, 686t, 1360t, 1361–1362, 1361t
for noncardiac chest pain, 1053
for painful neuropathies, 337
for postherpetic neuralgia, 384t, 386
for posttraumatic stress disorder, 444
side effects of, 402
for spinal cord injury pain, 589, 591
for tension-type headache, 1133
Venous sinus thrombosis, imaging of, 251, 254f, 255, 255f
Venous thoracic outlet syndrome, 267, 576, 1176. See also Thoracic outlet
syndrome
Venous ulcers, 550–551, 551f
Ventral horn, of spinal cord, 41
Ventral noradrenergic bundles (VNBs), 414, 414f, 416–417, 416f
Ventral posterior inferior (VPI) nucleus, 65, 108
Ventral posterior medial (VPM) nucleus, 108
Ventral posterolateral (VPL) nucleus, 65, 110
deep brain stimulation of, 65, 1587–1589
Ventral tegmental area (VTA), 64, 414, 1002–1003, 1003f
Ventrolateral funiculi (VLFs), 55
Ventrolateral orbital cortex (VLO), 55t, 57
Ventrolateral pathways, of axonal projections, 43, 44
Ventromedial (VM) nucleus, 108
Ventromedial pathways, of axonal projections, 44
Verapamil
for cluster headache, 1026–1027, 1027t, 1134
for hypnic headache, 1028
for noncardiac chest pain, 1052
Verbal Descriptor Scale (VDS), 1733

5887
Verbal Rating Scale (VRS), 276, 276f, 288, 289, 321
for cancer pain, 636
for central pain states, 397
Veritable energies, 1552–1553
Vermont, physician-assisted death in, 202
Vertebrae, thoracic, anatomy of, 1180, 1181f, 1182f
Vertebral arteries, 1142–1143, 1144f, 1145f
Vertebral augmentation, 711t, 725–727, 726f, 748
Vertebral canal, 1142, 1144f
Vertebral compression, 1197t
Vertebral fractures
arthritis and, 495
bone metastases and, 744
chest wall pain with, 1187, 1197t
compression, 259–261, 1187, 1187f
group therapy for pain in, 1447t
Vertebral metastases, 645t, 661–663, 722–776, 773f, 774f, 775f
Vertebroplasty, 725–727, 748
Vertigo, chronic, diagnostic imaging in, 258, 260f
Vestibulocochlear nerve, 1162t
Vestibulodynia, 1091–1092
Vestibulospinal tract, 40f
Veterans, PTSD and pain in, 443–444, 1411
Veterans Healthcare Administration (VHA), interdisciplinary chronic pain
management in, 1714–1715
VGCCs. See Voltage-gated calcium channels
VGSCs. See Voltage-gated sodium channels
Vibration sense, 235
Vicarious learning, in group therapy, 1464
Vidarabine, for herpes zoster, 378
Vide supra, 418
Vigilance
in abdominal pain, 1067, 1068, 1070
in anxiety, 80
in emotion and noxious signaling, 415

5888
 in low back pain, 1247, 1248f, 1256
in pain processing, 70–71
Vigilance network, 70
VIP. See Vasoactive intestinal peptide
Viral culture, in herpes zoster, 374
Viral DNA testing, in herpes zoster, 374
Viral infection, neuraxial techniques and, 852–853
Virtual reality
for burn pain, 905–906, 906f
for hypnosis, 1426
for phantom pain, 368
Visceral afferent system, 103, 114, 753, 1065, 1065f
Visceral hypersensitivity
in abdominal pain, 1066, 1068
in chronic pelvic pain, female, 1086
in noncardiac chest pain, 1037, 1039–1040
Visceral organs
sensation in, 114
sympathetic and nociceptive nerve supply to, 115t–117t
Visceral pain
abdominal (See Abdominal pain)
anatomy and physiology in, 751–752
ascending pathways of, 753–754
cancer-related, 603, 613–614, 615t, 625–626, 628, 651–653, 751–762
chemotherapy and, 756, 757
in children, 793
descriptions by site, 652–653
diagnosis of, 623–625
epidemiology of, 751
iatrogenic causes of, 752
inflammatory, 751–752
ischemic, 751–752
localization of, 652
mechanical, 751–752
mechanism of, 651–652

5889
 pain syndromes in, 754–757
pharmacotherapy for, 757–759
procedural interventions for, 759–760
radiation therapy and, 756–757
surgery for, 759–760
treatment of, 757–760
true v. referred, 652
central processing of, 1066
characteristics of, 751–754
chest, 1180
classes of, 751
definition of, 628, 651
dorsal rhizotomy or ganglionectomy for, 1682
intensity coding in, 1065
localization of, 753
mechanisms of, 1064–1066
nociception in, 1065–1066
pelvic, male, 1099, 1100t
psychological processing of, 752
sensitization in, 752
somatic pain v., 103–106, 106t, 1062, 1064–1065
specificity coding in, 1065
spinal cord injury and, 110, 584, 585f, 587f, 590, 1578
spinal cord stimulation for, 1576, 1577f
Visceral pain adjuvants, 686–687
Viscerosomatic convergence, 751
Visual Analog Scale (VAS), 229, 276, 276f, 288, 321
for cancer pain, 636, 736
pediatric, 790
for central pain states, 397
for dying patients, 1733
for emergency department assessment, 1771–1772
for GERD-related chest pain, 1051
for HIV pain, 992
for low back pain, 1250

5890
 for spine surgery candidates, 1304
Visual Analogue Scale for Fatigue, 632t
Visual illusion, 403
Vital force, 3
Vitamin B, for livedoid vasculitis, 548
Vitamin B2, for headache prevention, 922
Vitamin B12, for myofascial pain, 516
Vitamin C, and complex regional pain syndrome, 352
Vitamin D, 95, 514–515, 1167
Vitamin K, for warfarin skin necrosis, 549
VLFs. See Ventrolateral funiculi
VLO. See Ventrolateral orbital cortex
VNBs. See Ventral noradrenergic bundles
Vocational counselor, 1712
Vocational disability, 231
Vocational history, 231, 295
Vocational rehabilitation, 351, 1491, 1501
Vocational Rehabilitation Act of 1923, 1491
VOCS. See Vascular occlusive crisis
Volitional approach, in behavioral change, 1476–1477
Voltage-gated calcium channels (VGCCs), 31–32, 50
Voltage-gated sodium channels (VGSCs), 25, 30–31, 34, 50
Voltaren, 1318, 1319t
Vomiting
abdominal pain and, 1064
in cancer patients, 617, 683–684
antiemetics for, 683–684, 684t
chemotherapy-induced, 683, 684
opioid-induced, 683–684, 684f
radiation therapy–induced, 683
neuraxial administration and, 835–836
opioid-induced, 1337
von Frey, Max, 5, 5f, 6
von Gerhardt, Charles, 8
VPI. See Ventral posterior inferior (VPI) nucleus

5891
VPL. See Ventral posterolateral (VPL) nucleus
VPM. See Ventral posterior medial (VPM) nucleus
VRS. See Verbal Rating Scale
VTA. See Ventral tegmental area
Vulval pain, secondary, 1092, 1092t
Vulval Pain Society, 1092
Vulval pain syndromes, 1091–1092
classification and terminology, 1092
management of, 1092
Vulvodynia, 525, 534, 1088, 1091–1092

W
Waddell, G., biopsychosocial model of, 85
Waddell Disability Instrument, 1305
Waddell signs, 1166, 1168t
Wait list, group therapy as alternative to, 1442–1456
Waiting list control group, 125, 126
Wall, P. D., 6, 7f, 141
gate control theory of, 6, 18, 52, 60, 83, 1492 (See also Gate control
model)
Wallerian degeneration hypothesis, 1669
Walters, Allan, 2
War trauma, 838–839
levels of care in, 838, 838t
peripheral nerve catheters for, 838, 838t
Warfarin
for antiphospholipid syndrome, 548
bleeding complications with, 1758
for livedoid vasculitis, 548
Warfarin (Coumadin) skin necrosis, 548–549
Warfarin-associated calciphylaxis, 550
Warfield, Carol, 1751
Warm and noxious heat, 235
Warm sensation, 397
Washington State
morphine equivalent daily dose in, 186, 310

5892
 opioid policy in, 307–311, 1516–1518
physician-assisted death in, 201–202
Washington State Agency Medical Directors’ Group, 829, 1518
Washington State Department of Labor and Industries, 302, 307–311
claim management in, 307
evaluation of workers for permanent benefits, 311
evaluation outcomes of, 311
opioid management in, 310–311
programs to reduce disability, 308–309
SSDI/SSI v. state process, 307
Washington v Glucksberg, 201–202
Water injections, intradermal, for childbirth pain, 945–946, 945f
Waterloo-Stanford Group C (WSGC), 1425
Weddell, G., 6
Wegener’s granulomatosis. See Granulomatosis with polyangiitis
Wegg, Lillian, 1491
Wegner’s ironic processes theory of mental control, 1396–1397, 1396t
Weight loss, for osteoarthritis, 489
Welcome, in patient interaction, 479–480, 479t
Wernicke’s encephalopathy, bariatric surgery and, 332
West Haven-Yale Multidimensional Pain Inventory (WHYMPI), 1304
Western Ontario and McMaster Universities Osteoarthritis Index, 129
Western Ontario McMaster Assessment of Knee and Hip Osteoarthritis
(WOMAC), 323
Wet cupping, 1530–1531
WHA. See World Health Assembly
Whiplash, 1233, 1235–1236
anatomy and pathophysiology of, 575
cervicogenic headache in, 1171
epidemiology of, 1158–1159
joints involved in, 1235–1236, 1236f
pain history in, 1231
recovery curve for, 1235, 1235f
sociocultural perspective on, 146
thoracic outlet syndrome in, 575, 576, 578

5893
White communicating ramus, 112, 113f, 114
White matter, of spinal cord, 39, 40f
Whitney, Eugene B., 195
WHO. See World Health Organization
Wholesale level, opioid diversion at, 187
WHYMPI. See West Haven-Yale Multidimensional Pain Inventory
Wide-dynamic range neurons, 42–43, 107, 1571, 1572f
Wide-field radiotherapy, 776–777
Widespread musculoskeletal pain, 921
Widespread pain, chronic, 13
Widespread Pain Index (WPI), 532, 533f
Wilk v. American Medical Association, 1546
Wilkes Staging System, in TMJ disorders, 1133t
Willow bark, 1315
Willståtter, Richard, 1382
Wind-up, 15, 45, 53, 53f, 107, 236
Winnie, Alon, 1751
WIPS framework, for patient interaction, 479–480, 479t
Wireless pH system, for noncardiac chest pain, 1043
Withdrawal, 1017, 1340, 1508, 1764. See also specific drugs
in diagnostic criteria, 1510, 1510t
in intrathecal drug delivery, 1639
medically supervised, 1511
pathway of, 1002–1003
physical dependence and, 456–457
Withdrawal hyperalgesia, 457
WOMAC. See Western Ontario McMaster Assessment of Knee and Hip
Osteoarthritis
Women. See also Gender differences, in pain
HIV pain in, 985
pelvic pain in, 1079–1095
Wonderland (Plensa sculpture), 146, 146f
Wood, A., 8
Woolf, C. J., central sensitization model of, 53, 54f
Work, continuing or returning to, 445, 1255, 1491, 1501

5894
Work conditioning, 1501
Work disability
basic concepts in, 302
evaluation of, 302–312 (See also Disability evaluation)
Work hardening, 1501, 1502t
Work history, 238
Work Productivity and Activity Impairment Questionnaire, 232
Work rehabilitation, 1491, 1501, 1501t, 1502t, 1503t
Work status, as outcome measure, 129
Working-age adults, cancer and cancer pain in, 600
Work-related injuries, group therapy for, 1446t
World Health Assembly (WHA), 205, 219–220
World Health Organization (WHO)
on addiction/drug dependence, 178–179
analgesic ladder of, 205, 454
in cancer pain, 208, 676, 677, 679–681, 680f, 711, 738
in HIV pain, 205, 993, 993f
in sickle cell disease pain, 973, 973t
on anxiety and depression, 1414
biopsychosocial model of disability, 1492
on cancer pain management, 219, 677
on cancer pain management in children, 797–798
on cancer risk factors, 599
Expert Committee on Cancer Pain Relief and Active Supportive Care,
174
geographical regions of, 209, 210t
Global Burden of Disease Initiative, 484, 1298
on human rights, 173
on opioid access and control, 174, 206–221
adequate availability, 207–208
barriers to availability and access, 215–221
consumption data, 207–215, 208t, 209f, 211f–214f
essential medicines in, 206
improving availability and access, 220–221
recommendations, 219–220

5895
 on oral mucositis, 661, 661t, 795
on palliative care, 160, 205, 802
on right to pain relief, 158
on suicide prevention, 467
World Health Organization Region for Africa (AFRO), 209, 210t, 211f
World Health Organization Region for Europe (EURO), 209, 210t, 212,
213f
World Health Organization Region for South East Asia (SEARO), 209,
210t, 212, 214f
World Health Organization Region for the Americas (AMRO), 209, 210t,
212f
World Health Organization Region for the Eastern Mediterranean
(EMRO), 209, 210t, 212, 213f
World Health Organization Region for the Western Pacific (WPRO), 209,
210t, 212–215, 214f
World Health Organization World Mental Health Composite International
Diagnostic Interview (WHO WMH-CIDI), 631t
World Medical Association, 174
Worldview, pain as part of, 1–2
Worldwide Hospice and Palliative Care Alliance, 205
Worst-case analysis
in compliance/substance abuse, 1009–1010, 1012
in loss of follow-up, 128
Wound hematoma, in intrathecal drug delivery, 1634–1635
Wound infiltration
for acute pain, 837
for children, 817–818
WPI. See Widespread Pain Index
Wrist pain, after spinal cord injury, 583
Wrong surgery, and failed back surgery, 1288
WSGC. See Waterloo-Stanford Group C

X
Xanthine oxidase inhibitors, 500, 1224
Xerostomia, in cancer treatment, 735
Xiphoid cartilage syndrome, 1190

5896
Xiphoid process, 1181, 1181f
Xiphoidalgia, 1190, 1199t

Y
Yellow flags
in low back pain, 1256
in spinal cord injury, 581, 583t, 584
Yin and yang, 1553
Yoga
for cancer pain, 701
for cancer pain in children, 802
for elderly patients, 934, 935
for low back pain, 1541, 1543
Young adults, cancer and cancer pain in, 600
Yttrium-90, for bone pain in cancer, 747

Z
Zalcitabine, neuropathy associated with, 331
Ziconotide, intrathecal, 714t, 715, 1375, 1624, 1625t, 1631t
for central pain, 402
for spinal cord injury pain, 592
Zidovudine, myopathy with, 989
Z-line, 506–507
Zoledronic acid, for bone pain in cancer, 746–747, 782
Zolmitriptan
for cluster headache, 1027
for migraine, 990t–991t, 1024t
Zolpidem, for fibromyalgia, 537
Zonisamide, for neuropathic pain, 1365t, 1366
Zopiclone
as adjuvant analgesic, 685
for fibromyalgia, 537
Zoster sine herpete, 373
Zung Self-Rating Depression Scale, 630
Zygapophysial joint(s)
cervical, 1138, 1140, 1142, 1144f, 1164

5897
 cervical v. lumbar, 1141f
inspection and palpation of, 1164
referral patterns from, 1164, 1164f–1165f
Zygapophysial joint pain
cervical, 1235–1236, 1236f, 1602–1603, 1602f, 1603t
lumbar, 1260, 1274–1276, 1603–1605, 1603f, 1604f, 1605t

5898
Table of Contents
PART ONE: Basic Considerations 195
CHAPTER 1: Intellectual Milestones in Our
195
Understanding and Treatment of Pain
Pain Understood as Part of a Larger Philosophy or
196
Worldview
Mechanistic Views of Pain 200
19TH CENTURY—PAIN AS A SPECIFIC SENSE 202
AFFERENT SIGNALING 207
GATE CONTROL THEORY 209
Treatments for Pain 211
Cognitive Treatment for Pain 212
Pharmacologic Treatment of Pain 214
Anatomically Specific Treatments for Pain 215
The Specialty of Pain Medicine 218
ACKNOWLEDGMENTS 219
CHAPTER 2: Pain Terms and Taxonomies of Pain 223
Definition of Commonly Used Pain Terms 223
Taxonomies 236
EXPERT-BASED CLASSIFICATIONS OF PAIN 237
CLASSIFICATION BASED ON ANATOMY 239
CLASSIFICATION BASED ON DURATION 239
CLASSIFICATION BASED ON THE ETIOLOGY OF
240
PAIN
CLASSIFICATION BASED ON BODY SYSTEM 241
CLASSIFICATION BASED ON SEVERITY 241
CLASSIFICATION BASED ON FUNCTIONING 242
CLASSIFICATION BASED ON INTENSITY AND

5899
FUNCTIONING
CLASSIFICATION BASED ON PROGNOSIS 244
MECHANISM-BASED CLASSIFICATION OF PAIN 244
Multiaxial Classifications 246
Empirically Based Classification of the Psychological
246
Components of Pain
COMPREHENSIVE, MULTIDIMENSIONAL
CLASSIFICATION OF PAIN: INTERNATIONAL
249
ASSOCIATION FOR THE STUDY OF PAIN
TAXONOMY
COMPREHENSIVE, MULTIDIMENSIONAL
CLASSIFICATION OF PAIN: ACTTION-
AMERICAN PAIN SOCIETY AND ACTTION- 254
AMERICAN PAIN SOCIETY-AMERICAN
ACADEMY OF PAIN MEDICINE
INDUCTIVE EMPIRICALLY BASED
257
CLASSIFICATIONS OF PAIN
PSYCHOMETRIC CONSIDERATIONS 258
Conclusion 259
CHAPTER 3: Peripheral Pain Mechanisms and
263
Nociceptor Sensitization
Functional Characterization of Nociceptors 264
Identification of Putative Nociceptors 267
Nociceptor Characteristics 270
ANATOMY OF THE NOCICEPTOR 270
STIMULUS TRANSDUCTION 276
PASSIVE ELECTROPHYSIOLOGIC PROPERTIES
AND THE SPREAD OF THE GENERATOR 279
POTENTIAL
ACTION POTENTIAL GENERATION 280

5900
ACTION POTENTIAL GENERATION 280
ACTION POTENTIAL PROPAGATION 283
TRANSMITTER RELEASE 284
Nociceptor Sensitization 286
Clinical Implications of Nociceptor Function 291
CHAPTER 4: Substrates of Spinal Cord Nociceptive
305
Processing
Defining Nociceptive Systems 306
MODELS OF PAIN PROCESSING 306
METHODS OF NEURONAL CHARACTERIZATION 307
DEFINING NOCICEPTIVE SECOND-ORDER
308
NEURONS
DEVELOPMENT OF SENSORY SYSTEMS 309
Targets of Primary Afferent Input 310
GROSS ANATOMY OF THE SPINAL CORD 310
SPINAL LAMINAE 312
FUNCTIONAL CHARACTERIZATION OF
316
NOCICEPTIVE NEURONS
CLASSIFICATION ACCORDING TO SITE OF
318
PROJECTION
Targets of Axonal Projections 318
INTRASPINAL PATHWAYS 318
SPINOTHALAMIC TRACT 319
Ventrolateral (Anterolateral) Axonal Pathways 319
Neospinothalamic versus Paleospinothalamic 320
Laminar Distribution of Spinothalamic Tract Neurons 320
Functional Characterization of Spinothalamic Tract
322
Neurons
Dorsolateral and Ventromedial Axonal Pathways 322

5901
TRACTS 323

Ventrolateral (Anterolateral) Axonal Pathways 323

Features of Spinoreticular Neurons 324
Features of Spinomesencephalic Neurons 324
POSTSYNAPTIC DORSAL COLUMN NEURONS 324
OTHER ASCENDING PATHWAYS 325
Neurochemistry of Second-order Neurons 326
NEUROTRANSMITTERS FROM PRIMARY
326
AFFERENTS
Excitatory Amino Acids: Ionotropic Receptor/Channels 329
Metabotropic Glutamate Receptors 330
Substance P 330
Calcitonin Gene-Related Peptide 331
Cholecystokinin 332
Other Neuropeptides 332
Adenosine Triphosphate 332
Colocalization of Neurotransmitters 333
NEUROTRANSMITTERS FROM INTERNEURONS 333
Inhibitory Amino Acids 333
Opioids 334
Acetylcholine 335
Other Neurotransmitters within Interneurons 336
NEUROTRANSMITTERS FROM SUPRASPINAL
336
SOURCES
Serotonin (5-Hydroxytryptamine) 336
Noradrenaline 337
Other Neurotransmitters in Descending Systems 337
NEUROTRANSMITTERS FROM GLIA OR

5902
UNKNOWN SOURCES
OTHER IMPORTANT RECEPTORS/CHANNELS 339
What Is Important to the Clinician 340
ACKNOWLEDGMENTS 340
CHAPTER 5: Modulation of Spinal Nociceptive
345
Processing
Spinal Cord–Based Modulatory Mechanisms 346
ACUTE SEGMENTAL MODULATORY EFFECTS 346
HETEROSEGMENTAL MODULATORY SYSTEMS 347
C-FIBER WIND-UP AND CENTRAL
349
SENSITIZATION
Supraspinal Modulatory Systems 351
TONIC DESCENDING INFLUENCES 351
SUPRASPINAL SUBSTRATES MEDIATING THE
353
DESCENDING MODULATION OF PAIN
Periaqueductal Grey of the Mesencephalon and the
353
Rostral Ventral Medulla
Other Deep Brain Sites 358
Cortical Structures 360
SUMMARY OF SUPRASPINAL INFLUENCES 362
ON, OFF, AND NEUTRAL CELLS 363
Triggers of Clinical Hypersensitivity 364
ALLODYNIA AND HYPERALGESIA 364
INFLAMMATION-INDUCED HYPERSENSITIVITY
365
AND INHIBITORY SYSTEMS
STRESS-INDUCED ANALGESIA AND
367
HYPERALGESIA
NEUROPATHIC PAIN 368
OPIOID-INDUCED HYPERALGESIA 369

5903
CHAPTER 6: Supraspinal Mechanisms of Pain and
377
Nociception
Functional Imaging of Pain in Humans 378
METHODOLOGIES OF NONINVASIVE AND
INVASIVE FUNCTIONAL BRAIN IMAGING IN 378
PAIN
Brainstem 380
PERIAQUEDUCTAL GRAY MATTER—A KEY
382
STRUCTURE OF ENDOGENOUS ANALGESIA
MESOLIMBIC DOPAMINE SYSTEM 385
Hypothalamus 385
Thalamus 386
THE LATERAL PAIN SYSTEM—THE SENSORY-
386
DISCRIMINATIVE PATHWAY
SPINAL CONNECTIONS TO BRAINSTEM AND
MEDIAL THALAMUS—THE AFFECTIVE 387
PATHWAY
Cortex 388
SENSORY AREAS 389
Primary Somatosensory Cortex 389
Secondary Somatosensory Cortex 391
LIMBIC AREAS 392
Insular Cortex 392
Cingulate Cortex 394
Prefrontal Cortex 396
Amygdala 399
Hippocampus 400
Vigilance, Arousal, and Attention in Pain Processing 401
Pain Plasticity 404

5904
Summary and Conclusion 406

CHAPTER 7: Psychological Aspects of Pain 416

Cognitive Factors: Predispositions, Appraisals, Beliefs,
418
Perceived Control, and Self-efficacy
PREDISPOSITIONS 419
APPRAISAL AND BELIEFS 422
CATASTROPHIZING AND FEAR-AVOIDANCE
423
BELIEFS
PERCEIVED CONTROL AND SELF-EFFICACY 425
COPING 426
Stress and Autonomic Responses: Hypothalamic-
427
Pituitary-Adrenal Axis Dysregulation
Emotion 428
ANXIETY 429
DEPRESSION 432
ANGER AND HOSTILITY 433
Psychogenic Conceptualizations of Chronic Pain 437
PSYCHOGENIC VIEW 437
Behavioral Formulations 438
CLASSICAL CONDITIONING 438
OPERANT CONDITIONING 438
SOCIAL (OBSERVATIONAL) LEARNING 440
GATE CONTROL THEORY 441
Cognitive-Behavioral Perspective 442
TREATMENTS BASED ON THE COGNITIVE-
446
BEHAVIORAL PERSPECTIVE
Biopsychosocial, Contextual Model 446
Families and Family Systems Perspective 447

5905
Conclusion 448
CHAPTER 8: Individual Differences in Pain: The Roles
460
of Gender, Ethnicity, and Genetics
Sex and Gender Differences in Pain 464
CLINICAL PAIN 464
EXPERIMENTAL PAIN 468
RESPONSES TO PAIN TREATMENT 470
BIOPSYCHOSOCIAL MECHANISMS 473
Ethnic Group Differences in Pain 474
CLINICAL PAIN 475
EXPERIMENTAL PAIN 476
RESPONSES TO PAIN TREATMENT 477
BIOPSYCHOSOCIAL MECHANISMS 479
Genetic Contributions to Pain 480
CLINICAL PAIN 480
EXPERIMENTAL PAIN 481
Interactions among Individual Difference Factors 483
Conclusion 485
ACKNOWLEDGMENTS 486
CHAPTER 9: Functional Neuroanatomy of the
500
Nociceptive System
Organization of the Peripheral Nociceptive System 501
Peripheral Nervous System Structures of Pain Sensation 507
Functional Anatomy of the Central Nervous System 508
DORSAL HORN 509
SPINOTHALAMIC TRACT 511
THALAMUS 513
SENSORY CORTEX 514
DESCENDING PATHWAYS OF THE CENTRAL

5906
CENTRAL PAIN 516
CENTRAL PAIN AFTER SPINAL CORD INJURY 517
Autonomic Nervous System 519
PERIPHERAL AUTONOMIC NERVOUS SYSTEM 519
PARASYMPATHETIC DIVISION 520
CRANIAL PARASYMPATHETICS 522
SACRAL PARASYMPATHETICS 524
SYMPATHETIC (THORACOLUMBAR) DIVISION 525
Sympathetic Preganglionic Neurons 526
Sympathetic Postganglionic Neurons 527
SENSATION IN VISCERAL ORGANS 534
AUTONOMIC CENTERS IN THE CENTRAL
535
NERVOUS SYSTEM
TRANSMISSION IN THE PERIPHERAL
537
AUTONOMIC NERVOUS SYSTEM
PHYSIOLOGY OF THE AUTONOMIC NERVOUS
538
SYSTEM
ENTERIC NERVOUS SYSTEM 540
Conclusion 541
CHAPTER 10: Clinical Trials 547
Uncontrolled Studies Paradigm 548
CONTROL GROUPS: AN IMPROVEMENT OVER
552
THE CASE SERIES
Randomized Allocation of Treatment and Control
557
Groups
Other Methods for Reducing Bias in Clinical Trials 559
BASELINE SIMILARITY OF STUDY GROUPS 560
BLINDING 561
WERE GROUPS TREATED EQUALLY EXCEPT
562

5907
FOR THE EXPERIMENTAL TREATMENT?
LOW LOSS TO FOLLOW-UP AND INTENTION-TO-
563
TREAT ANALYSIS
Other Issues in Clinical Trials 565
MEASUREMENT OF OUTCOMES 565
REPORTING THE RESULTS 567
STATISTICAL POWER 568
GENERALIZABILITY OF RESULTS AND
569
EFFICACY VERSUS EFFECTIVENESS
SUBGROUP ANALYSES 570
EFFECTS OF FUNDING SOURCE 570
ASSESSMENT OF HARMS 572
TRIAL-BASED COST-EFFECTIVENESS ANALYSIS 573
Alternative Study Designs 573
CLUSTER TRIALS 573
CROSSOVER TRIALS 574
FACTORIAL DESIGN 575
New Directions in Clinical Trials 575
PRAGMATIC TRIALS 575
ENRICHED ENROLLMENT RANDOMIZED
576
WITHDRAWAL TRIALS
EXPERTISE-BASED TRIALS 576
COMPARATIVE EFFECTIVENESS 577
EQUIVALENCE AND NONINFERIORITY TRIALS 578
STEPPED WEDGE DESIGN 578
BAYESIAN STATISTICAL INFERENCE AND
579
ADAPTIVE DESIGNS
Systematic Reviews 579
Conclusion 581

5908
Systematic Reviews 579
Conclusion 581
PART TWO: Economic, Political, Legal, and Ethical
Considerations 589

CHAPTER 11: Transdermal Pain: A Sociocultural

589
Perspective
What Is Transdermal Pain? 592
Ethnicity, Race, Sex, Gender, Age: Whose Pain? 595
Across Cultures: Beliefs, Attitudes, Perceptions,
602
Behaviors
Pain and Narrative: Culture, Meaning, Ethics 607
Beyond the Gate: Consciousness and the Limits of a
610
Molecular Gaze
Pain and Globalization: Power, Money, Systems 613
Conclusion: Summary and Synthesis 619
ACKNOWLEDGMENT 621
CHAPTER 12: Ethical Issues in Pain Management 631
Pain, Suffering, and the Core Values of Health Care 632
THE DUTY TO RELIEVE PAIN AND SUFFERING 634
CURATIVE VERSUS PALLIATIVE PARADIGMS
634
OF PATIENT CARE
The Phenomenon of Undertreated Pain 636
IDENTIFYING THE BARRIERS TO PAIN RELIEF 637
Professional Barriers 637
Patient Barriers 644
Societal Barriers 645
Ethical Implications of the Barriers 646
Embracing a New Ethic of Pain Relief 647
Conclusion 653

5909
Patients
Introduction 658
THE QUEST FOR MORAL ORDER AMID
658
EXISTENTIAL DISORDER
THE CONTRIBUTIONS AND LIMITATIONS OF
659
ETHICAL ANALYSIS IN END-OF-LIFE CARE
The Transition from Curative to Palliative and End-of-
662
Life Care
NEGOTIATING TREATMENT PREFERENCES:
663
THE IDEAL DECISION-MAKING PROCESS
DEPARTURES FROM THE IDEAL 664
Prognosis and Clinical Judgment 664
Patients’ Attitudes and Values 665
Physicians’ Attitudes and Values 666
COMMUNICATION WITH PATIENTS ABOUT
TREATMENT PREFERENCES NEAR THE END OF 668
LIFE
Surrogate Decision Making 671
ASSESSING DECISIONAL CAPACITY 672
RULING OUT OR ELIMINATING REVERSIBLE
673
CAUSES OF INCAPACITY
IDENTIFYING A SURROGATE 673
THE SURROGATE’S ROLES AND
675
RESPONSIBILITIES
A REALISTIC PROCESS OF ADVANCE CARE
676
PLANNING
Three Basic Problems 677
A Realistic Approach 678
Responding to Demands for Nonbeneficial Treatment 681

5910
THE CLINICAL CONTEXT OF THE CONFLICT 683
DIFFERENTIAL DIAGNOSIS OF THE CONFLICT 684
Physician-Assisted Death 688
TERMINOLOGY 689
ETHICAL CONSIDERATIONS ALONG THE
690
CLINICAL SPECTRUM
TWO LEVELS OF RESPONSE: SOCIAL POLICY
692
AND CLINICAL CARE
Social Policy 693
Clinical Care 694
Conclusion: Beyond the Patient–Physician Dyad 695
CHAPTER 14: Laws and Policies Affecting Pain
700
Management in the United States
Introduction 700
PREVALENCE OF UNRELIEVED PAIN IS A
700
PUBLIC HEALTH PROBLEM
BARRIERS TO THE SAFE AND EFFECTIVE USE
OF OPIOID ANALGESICS FOR PAIN 702
MANAGEMENT
POLICIES GOVERNING THE USE OF OPIOID
703
ANALGESICS FOR PAIN MANAGEMENT
International Treaties: Establishing Balance between
706
Drug Control and Medical Use
US Federal Law: Preserving Balance between Drug
710
Control and Medical Use
THE FEDERAL FOOD, DRUG, AND COSMETIC
710
ACT
US FEDERAL CONTROLLED SUBSTANCES LAW 715
The Controlled Substances Act Ensures Availability of 718
Controlled Substances for Medical Purposes

5911
Medical Practice 719
The Controlled Substances Act Distinguishes Treatment
of Addiction from Treatment of Pain, but Legal 722
Definitions Create Confusion
The Controlled Substances Act and Regulations Do Not
724
Limit Prescription Amount or Duration
Regulations Implementing the Controlled Substances
Act Now Authorize a Greater Variety of Secure 726
Disposal Opportunities for Controlled Substances
US State Laws: Striving for Balance between Drug
727
Control and Medical Use
STATE PAIN POLICY DEVELOPMENT: AN
728
EMERGING TREND
EVALUATING THE QUALITY OF STATE PAIN
731
POLICY
Policy Evaluation Findings 731
A PROGRESS REPORT CARD TO MEASURE
CHANGES IN THE QUALITY OF STATE PAIN 739
POLICIES
Progress Report Card Findings 739
THE IMPORTANCE OF IMPROVING STATE PAIN
743
POLICY
The Need to Implement and Communicate Policy 744
Considering Additional US Policies 745
Taking Diversion into Account 748
Conclusions 751
CHAPTER 15: Litigation Involving Pain Management 768
Administrative Proceedings 770
IN THE MATTER OF DILEO 771
HOOVER V AGENCY FOR HEALTH CARE

5912
Administrative Proceedings 770
IN THE MATTER OF DILEO 771
HOOVER V AGENCY FOR HEALTH CARE 772
ADMINISTRATION
OREGON BOARD OF MEDICAL EXAMINERS V
774
BILDER
ACCUSATION OF EUGENE WHITNEY, MD 775
Civil Litigation 777
ESTATE OF HENRY JAMES V HILLHAVEN
778
CORPORATION
BERGMAN V CHIN, MD, AND EDEN MEDICAL
780
CENTER
TOMLINSON V BAYBERRY CARE CENTER, ET
783
AL.
Criminal Litigation 785
STATE V NARAMORE 786
Federal Criminal Prosecutions 791
UNITED STATES V ROSEN (1978) 791
UNITED STATES V HURWITZ 793
UNITED STATES V MCIVER 795
Constitutional Cases 797
Lessons from the Litigation 801
CHAPTER 16: International Access to Therapeutic
806
Opioids
Pain Relief Is Part of Cancer and HIV/AIDS Control 807
PAIN AND PALLIATIVE CARE 808
Opioids Are Essential Medicines and Controlled
809
Substances
GOVERNMENTS MUST ENSURE ADEQUATE
811
OPIOID AVAILABILITY
5913
Disparities in Opioid Consumption 814
MORPHINE EQUIVALENCE METRIC 816
GLOBAL OPIOID CONSUMPTION TRENDS 817
DISPARITIES IN CONSUMPTION BY INCOME
819
LEVEL
Regional Opioid Consumption Trends 819
WORLD HEALTH ORGANIZATION REGION FOR
822
AFRICA (AFRO)
WORLD HEALTH ORGANIZATION REGION FOR
822
THE AMERICAS (AMRO)
WORLD HEALTH ORGANIZATION REGION FOR
823
THE EASTERN MEDITERRANEAN (EMRO)
WORLD HEALTH ORGANIZATION REGION FOR
824
EUROPE (EURO)
WORLD HEALTH ORGANIZATION REGION FOR
825
SOUTHEAST ASIA (SEARO)
WORLD HEALTH ORGANIZATION REGIONS FOR
826
THE WESTERN PACIFIC (WPRO)
Barriers to Opioid Availability and Accessibility 827
KNOWLEDGE AND ATTITUDES ABOUT PAIN,
830
OPIOIDS, AND DEPENDENCE SYNDROME
Inadequate Education of Health Care Professionals 830
Concerns about Dependence Syndrome (Addiction) 830
Concerns about Potential Side Effects 832
Health Care Professionals’ Fear of Prosecution or
832
Sanction
EXCESSIVELY STRICT LAWS OR REGULATORY
833
POLICIES
MEDICATION DISTRIBUTION SYSTEM
835
BARRIERS

5914
AFFORDABILITY 837

United Nations’ Recommendations 838

Efforts to Address Barriers and Improve Opioid
842
Availability and Accessibility
Conclusion 847
PART THREE: Evaluation of the Pain Patient 856
CHAPTER 17: Evaluation of the Chronic Pain Patient 856
Introduction 856
GENERAL GUIDELINES FOR ASSESSMENT OF
861
PERSISTENT PAIN
Outline of a Multidimensional Assessment
862
Questionnaire for Persistent Pain History
SUMMARY OF SOME NONPROPRIETARY
864
QUESTIONNAIRES
OTHER POTENTIALLY USEFUL QUESTIONS TO
CONSIDER FOR GAUGING EFFECTIVENESS OF 864
THERAPY
SUMMARY OF PROPRIETARY QUESTIONNAIRES
864
TO CONSIDER
The Pain History 865
O: ONSET OF PAIN 866
P: PROVOCATIVE/PALLIATIVE 867
Q: QUALITY OR CHARACTER 867
R: REGION/RADIATION 867
S: SEVERITY/INTENSITY OF PAIN 868
T: TIMING OF PAIN 869
ALTERED PERCEPTION 869
Past Medical and Surgical History 870
MOOD ASSESSMENT 870

5915
COPING STRATEGIES 873
SLEEP DISORDERS 873
COGNITIVE IMPAIRMENT 874
VOCATIONAL HISTORY AND CURRENT
875
VOCATIONAL DISABILITY
HABITS 875
Risk of Opioid Misuse, Abuse, or Dependence 876
Assessment of Function 878
Current and Past Treatments 879
CURRENT AND PAST MEDICATIONS
INCLUDING OVER-THE-COUNTER 880
MEDICATIONS
ALLERGIES 880
INVESTIGATIONS AND CONSULTATIONS 880
Goals 880
Physical Examination 881
GENERAL EXAM: OBSERVE, IDENTIFY AND
882
DOCUMENT
SITE OF PAIN 882
Observe 882
Palpate 883
Test 883
NEUROLOGIC EXAM 883
Observe or Ask About 883
Palpate 884
Test 884
BEDSIDE METHOD FOR QUANTITATIVE
887
SENSORY TESTING
Light Touch 888

5916
Light Touch 888
Vibration 888
Punctate/Pinprick 889
Warm and Noxious Heat 889
Cool and Noxious Cold 889
Grading the Tests 889
CAVEATS TO QUANTITATIVE SENSORY
891
TESTING INTERPRETATION
FURTHER INVESTIGATIONS OR CONSULTS 892
Follow-up Visits 892
Conclusion 893
GOALS 903
Considering the Right Goal for You 903
Setting SMART Goals 903
Appendix 17.1: Initial Visit Questionnaire 894
Appendix 17.2: Pain Diagram 902
Appendix 17.3: Goal Setting 903
Appendix 17.4: Follow-up Questionnaire 905
CHAPTER 18: Electrodiagnosis in Pain Medicine 910
The Electrodiagnostic Laboratory 910
Electrodiagnostic Tests 912
NERVE CONDUCTION STUDIES 912
NEEDLE ELECTROMYOGRAPHY 919
Application in Selected Conditions 925
Conclusion 928
CHAPTER 19: Diagnostic Imaging of Pain 932
Headache 933
ACUTE HEADACHE 934
Computed Tomography Angiography and Magnetic

5917
Resonance Angiography
CHRONIC HEADACHE 941
INTRACRANIAL HYPOTENSION 944
INTRACRANIAL HYPERTENSION
945
(PSEUDOTUMOR CEREBRI)
Facial Pain 946
Spinal Pain 948
OVERVIEW 948
COMPRESSION FRACTURES 950
BENIGN VERSUS MALIGNANT;
950
INFECTION/INFLAMMATION
DISCOGENIC PAIN 952
Limb Pain and Magnetic Resonance Neurography 955
MAGNETIC RESONANCE NEUROGRAPHY 955
THORACIC OUTLET SYNDROME 961
PIRIFORMIS SYNDROME 962
PERIPHERAL NERVE ENTRAPMENT
963
SYNDROMES
Imaging Guided Injection 964
Future Application of Pain Imaging 965
Conclusion 967
CHAPTER 20: Measurement of Pain 974
Introduction 974
VALIDITY, RELIABILITY, AND UTILITY IN THE
975
CONTEXT OF PAIN ASSESSMENT
Validity 975
Reliability 977
Utility 978
HOW MANY PAIN PROBLEMS SHOULD BE 979

5918
ASSESSED? 979

WHICH PAIN DOMAIN(S) SHOULD BE

980
ASSESSED?
RECALL RATINGS VERSUS SUMMARY SCORES
982
FROM MULTIPLE RATINGS USING DIARIES
Measuring Pain’s Domains 987
MEASURING PAIN INTENSITY 987
Recommendations for Assessing Pain Intensity 988
MEASURING PAIN AFFECT 989
Recommendations for Assessing Pain Affect 992
MEASURING PAIN QUALITY 992
Using Pain Quality Measures as Diagnostic Aides 993
Strengths and Weaknesses of Pain Quality Measures as
995
Diagnostic Aids
Pain Quality Scales as Descriptive and Outcome
996
Measures
Strengths and Weakness of Descriptive and Outcome
1009
Measures of Pain Quality
MEASURING PAIN’S SPATIAL
1010
CHARACTERISTICS
Recommendations for Assessing Pain Site 1012
MEASURING PAIN’S TEMPORAL
1012
CHARACTERISTICS
Recommendations for Assessing Pain’s Temporal
1014
Characteristics
MEASURING PAIN INTERFERENCE 1014
Brief Pain Inventory Pain Interference Scale 1014
Patient-Reported Outcomes Measurement Information
1017
System Pain Interference Item Bank and Short Forms

5919
Measuring Pain in Special Populations 1019
SIMPLIFIED MEASURES OF PAIN 1019
Simple Pain Measures to Consider 1019
Selecting the Best Measure for a Patient or Population 1021
BEHAVIOR OBSERVATION MEASURES 1023
Measuring Pain in Busy Clinical Settings 1024
Summary and Conclusions 1024
CHAPTER 21: Pain Psychology Evaluation 1038
Psychosocial History 1038
EARLY LIFE EXPERIENCES 1039
VOCATIONAL HISTORY 1039
EDUCATIONAL HISTORY 1040
Current Functioning 1041
BELIEF STRUCTURES 1041
SOCIAL SUPPORT 1043
CULTURAL FACTORS 1044
Substance Use 1044
NICOTINE 1045
ALCOHOL 1046
PRESCRIBED AND NONPRESCRIBED DRUG USE 1047
Psychiatric Functioning 1048
BEHAVIORAL OBSERVATIONS 1049
DEPRESSION 1049
ANXIETY 1050
POSTTRAUMATIC STRESS DISORDER 1051
SOMATIZATION 1052
Psychological Screening for Advanced Interventional
1052
Procedures
Conclusion 1053

5920
Procedures 1052
Conclusion 1053
CHAPTER 22: Disability Evaluation of Patients with
1060
Chronic Pain
Basic Concepts 1060
Conceptual and Empirical Issues 1061
IMPAIRMENT AND DISABILITY 1062
Impairment 1062
Disability 1062
ASSOCIATIONS BETWEEN IMPAIRMENT AND
1064
DISABILITY
THE “EMBEDDEDNESS” PROBLEM 1065
PRACTICAL PROBLEMS IN IDENTIFYING THE
ROLE OF PAIN IN DISABILITY 1066
DETERMINATIONS
Methods for Evaluating Chronic Pain in Applicants for
1068
Disability Benefits
EVALUATION METHODS IN THE SOCIAL
1068
SECURITY ADMINISTRATION
OUTCOMES OF SOCIAL SECURITY
1073
ADMINISTRATION EVALUATIONS
DISABILITY EVALUATION AND DISABILITY
MANAGEMENT IN THE WASHINGTON STATE 1074
DEPARTMENT OF LABOR AND INDUSTRIES
WASHINGTON STATE DEPARTMENT OF LABOR
AND INDUSTRIES PROGRAMS TO REDUCE 1077
DISABILITY
METHODS USED BY WASHINGTON STATE
DEPARTMENT OF LABOR AND INDUSTRIES TO
1087
EVALUATE INJURED WORKERS FOR

5921
OUTCOMES OF WASHINGTON STATE 1089
DEPARTMENT OF LABOR AND INDUSTRIES
EVALUATIONS
Conclusion 1090
CHAPTER 23: Multidisciplinary Assessment of
1094
Patients with Chronic Pain
Conceptual Issues 1094
CONUNDRUMS IN THE ASSESSMENT OF PAIN 1094
A CONCEPTUAL MODEL FOR ASSESSING PAIN 1095
Pain Behavior 1096
Classes of Variables Underlying Pain Behavior 1096
Assessment of Medical Factors 1097
ARE THERE RED FLAGS? 1099
ARE THERE RISK FACTORS FOR DELAYED
1104
RECOVERY?
SPECIFIC EVALUATION PROCEDURES 1105
History 1105
Physical Examination 1106
Ancillary Studies 1106
CONCLUSION 1107
Assessment of Central Nervous System Sensitization 1108
Assessment of Psychosocial Factors 1110
PSYCHOLOGICAL FACTORS AS CAUSES
1110
VERSUS CONSEQUENCES OF CHRONIC PAIN
Psychological Factors as Causal Agents in Development
1110
of Chronic Pain
Psychological Consequences of Chronic Pain 1111
ELEMENTS OF THE PSYCHOLOGICAL
1112
EVALUATION
Interviews 1114
5922
Interviews 1114
Self-report Inventories 1116
PROBLEM AREAS TO ASSESS 1117
Assessment of Pain 1117
Assessment of Overt Expressions of Pain 1119
Assessment of Emotional Distress 1121
Assessment of Fear 1122
Assessment of Beliefs, Coping, and Psychosocial
1123
Adaptation to Pain
Assessing Functional Impact 1124
SELF-REPORT MEASURES OF FUNCTION 1125
Assessment of Physical Capacity 1126
Assessment of Social Factors 1127
Organization of Multidisciplinary Evaluations 1128
Conclusion 1128
PART FOUR: Pain Conditions 1138
NEUROPATHIC PAIN CONDITIONS 1138
CHAPTER 24: Painful Neuropathies 1138
Pain as a Symptom of Neuropathy 1138
The Evaluation and Diagnosis of Neuropathy 1138
NEUROPATHY CLASSIFICATION 1138
HISTORY, EXAMINATION, AND DIAGNOSTIC
1141
STUDIES
Painful Neuropathies 1144
DISTAL SYMMETRIC POLYNEUROPATHIES 1144
Metabolic Causes 1144
Infectious Causes 1145
Toxic Neuropathies 1146
Nutritional Neuropathies 1147

5923
DEPENDENT NEUROPATHIES 1152
Neuropathy with Paraproteinemia 1152
Autoimmune Demyelinating Neuropathies 1153
PAINFUL MONONEUROPATHY MULTIPLEX AND
1156
FOCAL NEUROPATHIC SYNDROMES
Vasculitic Neuropathy 1156
Neuralgic Amyotrophy 1157
Diabetic Amyotrophy 1158
Other Diabetic Mononeuropathies 1159
SENSORY NEURONOPATHIES 1159
Postherpetic Neuralgia 1159
Sjögren’s Syndrome 1160
Paraneoplastic Sensory Neuronopathy 1161
Toxic Neuronopathy 1161
Treatment of Painful Neuropathies 1161
GENERAL PRINCIPLES OF THERAPY 1161
ANALGESIA THERAPY: GUIDELINES FOR
1161
PHARMACOTHERAPY
Tricyclic Agents 1163
α2δ Ligands 1164
Serotonin and Norepinephrine Reuptake Inhibitors 1165
Opioids 1165
Tramadol and Tapentadol 1166
Other Pharmacologic Agents 1166
Cannabinoids 1167
Topical Agents 1168
Principles of Pharmacotherapy for Pain from
Neuropathy 1168

5924
Neuropathy
Unresolved Questions 1169

CHAPTER 25: Complex Regional Pain Syndrome 1177

Epidemiology 1177
Pathophysiology 1179
ANIMAL MODELS 1179
HUMAN MODELS 1180
INFLAMMATION 1181
IMMUNOLOGIC FACTORS 1183
Afferent Dysfunction 1184
CENTRAL DYSFUNCTION 1185
SYMPATHETIC DYSFUNCTION 1186
TROPHIC, DYSTROPHIC, AND NUTRITIONAL
1189
ABNORMALITIES
MOTOR AND MOVEMENT DISORDERS 1190
IMMOBILIZATION AND DISUSE 1192
Genetics 1192
A Convergent Pathophysiologic Theory 1193
Diagnosis 1194
THE INTERNATIONAL ASSOCIATION FOR THE
1194
STUDY OF PAIN CRITERIA
THE BUDAPEST CRITERIA 1197
SEQUENTIAL STAGES AND SUBSETS OF
1200
COMPLEX REGIONAL PAIN SYNDROME
PSYCHOLOGICAL FACTORS IN COMPLEX
1202
REGIONAL PAIN SYNDROME
Treatment 1206
THE RATIONALE FOR FUNCTIONAL
1207
RESTORATION

5925
MODALITIES
PHARMACOTHERAPY 1213
PSYCHOLOGICAL INTERVENTIONS 1218
INTERVENTIONAL THERAPIES 1221
OTHER THERAPEUTIC MODALITIES 1224
CHAPTER 26: Phantom Pain 1246
Epidemiology 1247
Modulation of Phantom Pain 1248
Pathophysiology of Phantom Pain 1248
Prevention of Phantom Pain 1252
Treatment of Phantom Pain 1252
Pharmacologic Interventions 1253
ANTIDEPRESSANTS 1253
ANTIEPILEPTIC DRUGS 1254
OPIOIDS 1255
NMDA RECEPTOR ANTAGONISTS 1256
CALCITONIN 1257
TRANSIENT RECEPTOR POTENTIAL CATION
CHANNEL SUBFAMILY V MEMBER 1 (TRPV1) 1257
MODULATORS
INTERVENTIONAL THERAPY 1258
NEUROMODULATION 1260
SURGICAL INTERVENTIONS 1262
BEHAVIORAL MEDICINE INTERVENTIONS 1263
MISCELLANEOUS TREATMENTS FOR RESIDUAL
1265
LIMB PAIN
Summary 1266
CHAPTER 27: Herpes Zoster and Postherpetic 1274
Neuralgia

5926
Neuralgia
Clinical Picture and Natural History of Herpes Zoster 1275

PRODROME 1275
RASH 1275
PAIN 1276
DISTRIBUTION OF HERPES ZOSTER 1277
CLINICAL VARIANTS 1278
Herpes Zoster Ophthalmicus 1278
Herpes Zoster Oticus (Ramsay-Hunt Syndrome) 1278
Zoster Sine Herpete 1279
Diagnosis of Herpes Zoster 1279
LABORATORY TESTING 1280
Viral Culture 1280
Direct Immunofluorescence Assay 1280
Viral DNA Testing 1280
Biopsy 1281
Testing for Underlying Disorders 1281
Epidemiology of Herpes Zoster 1281
Pathophysiology of Herpes Zoster and Mechanisms of
1283
Acute Pain
Complications Associated with Herpes Zoster 1285
OPHTHALMIC COMPLICATIONS 1285
MOTOR NEUROPATHY 1285
RARE NEUROLOGIC COMPLICATIONS 1286
VISCERAL COMPLICATIONS 1287
DECREASED QUALITY OF LIFE 1287
Treatment of Herpes Zoster 1287
PATIENT EDUCATION 1287

5927
ANALGESIC TREATMENT 1291
CORTICOSTEROIDS 1294
Lidocaine Patch 1295
NEURAL BLOCKADE 1295
COMPLEMENTARY AND ALTERNATIVE
1296
MEDICINE
SPINAL CORD STIMULATION 1297
Prevention of Herpes Zoster 1297
CHILDHOOD VACCINATION 1297
VARICELLA-ZOSTER IMMUNOGLOBULIN 1298
HERPES ZOSTER VACCINATION FOR ADULTS 1298
Clinical Picture of Postherpetic Neuralgia 1300
DIAGNOSIS AND ASSESSMENT OF
1301
POSTHERPETIC NEURALGIA
Laboratory Diagnosis 1302
Epidemiology and Natural History of Postherpetic
1303
Neuralgia
RISK FACTORS FOR POSTHERPETIC
1303
NEURALGIA
Pathophysiology of Postherpetic Neuralgia 1304
Treatment of Postherpetic Neuralgia 1308
ANTICONVULSANTS: GABAPENTIN AND
1311
PREGABALIN
ANTIDEPRESSANT MEDICATIONS 1315
Tricyclic Antidepressants 1315
Selective Serotonin and Norepinephrine Reuptake
1316
Inhibitors (Dual Reuptake Inhibitors)
OPIOID ANALGESICS 1316
TRAMADOL 1318

5928
TRAMADOL 1318
TAPENTADOL 1318

TOPICAL THERAPIES 1319

Topical Lidocaine 1320
Topical Capsaicin 1320
Other Topical Treatments 1322
COMBINATION THERAPY 1322
N-METHYL-D-ASPARTIC ACID ANTAGONISTS 1323
OTHER PHARMACOLOGIC THERAPIES 1323
INVASIVE TREATMENTS FOR POSTHERPETIC
1323
NEURALGIA
Botulinum Toxin 1324
Dorsal Root Ganglion Blocks 1325
Peripheral Nerve Blocks 1325
Neuroaugmentive Techniques 1326
Sympathetic Nerve Blocks 1327
Neuraxial Blocks 1327
PSYCHOLOGICAL INTERVENTIONS 1328
ELECTROANALGESIA 1328
Transcutaneous Electrical Nerve Stimulation 1328
Scrambler Therapy 1328
Surgical Approaches 1329
Prevention of Postherpetic Neuralgia 1329
Conclusions 1331
CHAPTER 28: Central Pain States 1344
Diagnosis 1344
Clinical Characteristics 1347
Clinical Assessment 1349

5929
CENTRAL POSTSTROKE PAIN 1350
CENTRAL PAIN IN MULTIPLE SCLEROSIS 1351
CENTRAL PAIN IN SPINAL CORD INJURY 1351
OTHER CENTRAL PAIN CONDITIONS 1352
Preclinical Models 1353
Mechanisms 1354
Treatment of Central Pain 1357
PHARMACOLOGIC TREATMENT 1358
First-line Pharmacologic Treatments 1360
Second- and Third-Line Pharmacologic Treatments 1363
Other Drugs, Combination Therapy, and Intrathecal
1364
Drug Administration
PSYCHOLOGICAL AND PHYSIOTHERAPY
1365
TREATMENT
NEUROSURGICAL MANAGEMENT 1366
Targeted Drug Delivery 1366
Neuroablation 1367
Neuromodulation 1367
PSYCHOLOGICAL CONTRIBUTIONS TO PAIN 1384
CHAPTER 29: The Psychophysiology of Pain 1384
Historical Perspective: Mind–Body Issues 1386
Emotions: Definition and Mechanisms 1387
WHAT ARE EMOTIONS? 1387
EMOTION IN A SOCIOBIOLOGIC PERSPECTIVE 1388
ADAPTIVE FUNCTIONS OF EMOTION 1388
EMOTIONS AND BEHAVIOR 1389
THE CENTRAL NEUROANATOMY OF EMOTION:
1390
LIMBIC STRUCTURES
PERIPHERAL NEUROANATOMY OF EMOTION:
1392

5930
PERIPHERAL NEUROANATOMY OF EMOTION:
THE AUTONOMIC NERVOUS SYSTEM 1392

Autonomic Arousal and Subjective Experience 1393

The Role of Feedback 1393
Relationship of Central and Peripheral Mechanisms 1395
NOXIOUS SIGNALING AND CENTRAL LIMBIC
1396
PROCESSING
Central Neurotransmitter Systems 1397
LOCUS COERULEUS AND THE DORSAL
1398
NORADRENERGIC BUNDLE
THE VENTRAL NORADRENERGIC BUNDLE AND
THE HYPOTHALAMO-PITUITARY- 1402
ADRENOCORTICAL AXIS
PRIMARY AND SECONDARY FEATURES OF THE
1405
AFFECTIVE DIMENSION OF PAIN
SUMMARY OF THE CONSTRUCTION AND
1406
MODULATION OF PAIN
Emotion and Cognition 1408
The Sense of Self 1409
COGNITIVE PERSPECTIVE 1409
MULTIPLE PERSPECTIVES ON THE SELF 1409
Stress, Sickness, and Pain 1411
BASIC DEFINITIONS: STRESS, HOMEOSTASIS,
1411
AND ALLOSTASIS
PHYSIOLOGIC MECHANISMS OF STRESS 1413
Neural Substrates 1414
Immune Mechanisms 1415
The Sickness Response 1416
The Sickness Response and Depression 1417

5931
STRESS AND CHRONIC PAIN 1418
Future Directions 1419
CHAPTER 30: Pain and Learning 1429
Overview of the Three Major Principles of Learning 1429
CLASSICAL CONDITIONING 1429
OPERANT CONDITIONING 1431
OBSERVATIONAL LEARNING 1432
Operant Conditioning and Pain 1433
THE HALLMARK WORK OF WILBERT FORDYCE 1433
OPERANT CONDITIONING AND CHRONIC PAIN:
1436
THE BASICS
Classical Conditioning and Pain 1437
AVERSIVE CLASSICAL CONDITIONING AND
1437
PAIN
CLASSICALLY CONDITIONED
1437
FEAR/AVOIDANCE AND PAIN
Observational Learning and Pain 1438
Integrating Learning Principles in the Treatment of Pain 1440
COGNITIVE-BEHAVIORAL THERAPY AND PAIN 1440
COGNITIVE-BEHAVIORAL THERAPY AS AN
ESSENTIAL COMPONENT OF A
1441
COMPREHENSIVE INTERDISCIPLINARY
APPROACH TO PAIN MANAGEMENT
Conclusion 1442
CHAPTER 31: Psychiatric Illness, Depression, Anxiety,
1445
and Somatic Symptom Disorder
Psychiatric Nosology and Diagnostic and Treatment
1446
Approaches
Framework for Describing Psychiatric Symptoms 1452

5932
Framework for Describing Psychiatric Symptoms 1452
Depression 1455

SUICIDAL IDEATION AND BEHAVIOR 1456

WHICH CAME FIRST, DEPRESSION OR PAIN? 1458
DIFFERENTIAL DIAGNOSIS 1460
BIOLOGIC TESTS FOR DEPRESSION 1460
DYSTHYMIC DISORDER 1461
EPIDEMIOLOGY OF DEPRESSION 1461
PAIN AND DEPRESSION: MECHANISMS OF
1463
ASSOCIATION
Biologic Theories 1463
Psychological Theories 1467
Anthropologic Theories 1471
DEPRESSION TREATMENT 1472
Pharmacologic Agents 1472
PSYCHOTHERAPY 1476
Psychodynamic Psychotherapy 1476
Behavioral Model 1476
Cognitive Model 1477
Cognitive-Behavioral Model 1478
Anxiety Disorders 1479
GENERALIZED ANXIETY DISORDER 1480
PANIC DISORDER 1482
EPIDEMIOLOGY 1483
TREATMENT 1485
Posttraumatic Stress Disorder 1486
DIAGNOSIS 1486
EPIDEMIOLOGY OF POSTTRAUMATIC STRESS
1488

5933
POSTTRAUMATIC STRESS DISORDER AND 1489
ASSOCIATIONS WITH PAIN
TREATMENT 1489
Personality Disorders 1490
EPIDEMIOLOGY 1490
OVERVIEW OF PERSONALITY DISORDERS 1491
PERSONALITY AND PAIN TREATMENT
1493
OUTCOME
Somatic Symptom Disorders, Illness Behavior, and Sick
1494
Role
DEFINITIONS 1494
OVERVIEW OF SOMATOFORM DISORDERS AND
1496
SOMATIC SYMPTOM DISORDERS
Somatic Symptom Disorder 1498
Conversion Disorder (Functional Neurologic Symptom
1499
Disorder)
ILLNESS ANXIETY DISORDER 1502
Conclusion: Pain and Suffering and Psychiatry 1503
CHAPTER 32: Treatment of Pain in Patients with
1517
Addiction
Substance Use Disorder 1518
Clinical Implications of Substance Use Disorders on
1521
Pain
NEUROBIOLOGIC OVERLAP BETWEEN PAIN
1521
AND ADDICTION SYSTEMS
Tolerance 1522
Dependence 1523
Analgesic Effects of Drugs of Abuse 1524
EFFECTS OF SUBSTANCE USE DISORDER ON
PAIN 1525

5934
EFFECTS OF SUBSTANCE USE DISORDER ON 1525
PAIN
EFFECTS OF OPIOID USE DISORDER ON PAIN 1526
Genetics of Pain and Opioid Use Disorder 1527
Tolerance 1528
Physical Dependence 1529
Opioid-Induced Hyperalgesia 1530
Pain Management in Persons with Substance Use
1542
Disorder
PREVALENCE OF SUBSTANCE USE DISORDERS
1543
IN PATIENTS WITH PAIN
PRINCIPLES OF PAIN TREATMENT IN PATIENTS
1546
WITH SUBSTANCE USE DISORDERS
Provide Effective Pain Relief 1546
Reinforce or Introduce Substance Use Disorder
1560
Treatment
Document Pain Treatment Plan and Involve Patient and
1562
Family in the Plan of Care
Pain, Substance Use Disorder, and Suicide 1562
Conclusions 1571
CHAPTER 33: The Doctor–Patient Relationship in Pain
Management: Dealing with Difficult Clinician–Patient 1590
Interactions
Difficult Patients and Difficult Doctor–Patient
1591
Relationships
PSYCHIATRIC AND PERSONALITY ISSUES 1592
OPIOID THERAPY 1594
DIFFICULT “NORMAL” PATIENTS 1595
COMORBID MEDICAL CONDITIONS 1595
SUBSTANCE USE DISORDERS 1596

5935
Health Care System Factors 1598
Patient Interaction Strategies 1599
PATIENT-FOCUSED CARE 1600
Communication Framework: WIPS and E’s 1602
Clinical Scenarios 1604
SCENARIO 1 1604
SCENARIO 2 1605
SCENARIO 3 1606
SCENARIO 4 1606
SCENARIO 5 1607
SCENARIO 6 1608
SCENARIO 7 1609
Summary and Conclusions 1610
ACKNOWLEDGMENT 1610
VASCULAR, CUTANEOUS, AND
1615
MUSCULOSKELETAL PAINS
CHAPTER 34: Arthritis 1615
Basic Considerations 1615
PROBLEM IN PERSPECTIVE 1615
JOINT ANATOMY 1616
Nerve and Blood Supply 1618
Clinical Approach to Joint Pain 1619
HISTORY 1619
Number of Joints Affected 1620
Pattern Recognition 1622
Systemic Features of Arthritis 1622
PHYSICAL EXAMINATION 1623
EXAMINATION OF SYNOVIAL FLUID 1623

5936
EXAMINATION OF SYNOVIAL FLUID 1623
Clinical Considerations 1624

OSTEOARTHRITIS 1624
Epidemiology and Pathophysiology 1624
Symptoms and Signs 1627
SECONDARY OSTEOARTHRITIS 1630
Laboratory Findings 1631
Treatment 1631
RHEUMATOID ARTHRITIS 1634
Etiology and Pathophysiology 1634
Symptoms and Signs 1635
Laboratory Findings 1637
Treatment Philosophy 1638
Current Management of Rheumatoid Arthritis 1639
Important Complications of Rheumatoid Arthritis
1643
Presenting with Pain
THE SPONDYLOARTHROPATHIES 1644
Ankylosing Spondylitis 1644
Spondylodiskitis 1648
REACTIVE ARTHRITIS 1649
Symptoms and Signs 1650
Laboratory Findings 1651
Treatment 1651
Complications of Reactive Arthritis Associated with
1651
Chronic Pain
PSORIATIC ARTHRITIS 1652
Symptoms and Signs 1652
Laboratory Findings 1653

5937
ARTHRITIS ASSOCIATED WITH 1654
INFLAMMATORY BOWEL DISEASE
Treatment 1655
ARTHRITIS CAUSED BY CRYSTALS 1655
Calcium Pyrophosphate Deposition Disease 1655
Pathophysiology 1655
Symptoms and Signs 1656
Treatment 1657
URATE GOUT 1658
Etiology and Pathophysiology 1658
Pathophysiology of Acute Gouty Arthritis 1660
Signs and Symptoms 1662
Laboratory Findings 1664
Treatment 1664
INFECTIOUS ARTHRITIS 1667
Nongonococcal Bacterial Arthritis 1667
Gonococcal Arthritis 1670
POLYMYALGIA RHEUMATICA 1671
CHAPTER 35: Myofascial Pain Syndrome 1677
Brief Historical Overview 1678
Basic Myofascial Pain Concepts 1680
Muscle Physiology 1683
The Motor Endplate 1685
Sensitization and Activation of Muscle Nociceptors 1689
Central Sensitization 1691
The Biochemical Milieu of Myofascial Trigger Points 1698
pH and Muscle Pain 1698
Neuropeptides, Inflammatory Mediators, and Tissue
Injury and Pain 1699

5938
Neuropeptides, Inflammatory Mediators, and Tissue 1699
Injury and Pain
Catecholamines and the Autonomic Nervous System 1701
Cytokines and Pain 1701
Clinical Management 1703
TRIGGER POINT DIAGNOSIS 1703
PHYSICAL EXAMINATION AND DIAGNOSIS 1705
TREATMENT OPTIONS 1710
Patient Education 1710
Physical Therapy 1711
Needling Therapies 1712
NONINVASIVE TREATMENT OPTIONS 1717
Summary 1718
CHAPTER 36: Fibromyalgia: A Discrete Disease or the
1739
End of the Continuum
Historical Perspective 1741
Epidemiology 1743
CHRONIC WIDESPREAD PAIN 1743
FIBROMYALGIA 1743
SIGNIFICANCE OF TENDER POINTS 1744
OTHER FEATURES OF FIBROMYALGIA
GLEANED FROM EPIDEMIOLOGIC OR 1745
OBSERVATIONAL STUDIES
Etiology 1750
ANIMAL MODELS OF FIBROMYALGIA 1750
GENETIC FACTORS 1750
EVIDENCE OF CENTRAL NERVOUS SYSTEM
DISTURBANCES IN PAIN AND SENSORY 1752
PROCESSING

5939
STIMULI
BRAIN IMAGING STUDIES 1753
THE ROLE OF NEUROENDOCRINE OR
1757
AUTONOMIC ABNORMALITIES
THE ROLE OF PERIPHERAL FACTORS IN
1758
FIBROMYALGIA
EVIDENCE OF ABNORMAL CYTOKINES OR OF
1759
IMMUNE DYSFUNCTION IN FIBROMYALGIA
THE ROLE OF “SMALL FIBER NEUROPATHY” IN
1759
FIBROMYALGIA
Diagnosis 1760
DIAGNOSIS OF FIBROMYALGIA 1760
Treatment 1768
GENERAL APPROACH 1768
PHARMACOLOGIC THERAPY 1772
Tricyclic Agents 1773
Serotonin and Norepinephrine Reuptake Inhibitors 1773
Anticonvulsants 1775
Combination Drug Therapy 1776
Other Central Nervous System–Acting Drugs 1776
Classic Analgesics 1777
NEUROSTIMULATORY THERAPIES 1778
NONPHARMACOLOGIC THERAPIES 1779
Prognosis 1780
Conclusion 1781
Key Points 1781
CHAPTER 37: Pain of Dermatologic Disorders 1793
Basic Considerations: Anatomy and Physiology of the
Skin 1796

5940
Basic Considerations: Anatomy and Physiology of the 1796
Skin
Clinical Disorders 1799
LEUKOCYTOCLASTIC VASCULITIS 1799
Etiology 1800
Pathogenesis 1800
Treatment 1801
POLYARTERITIS NODOSA 1801
Symptoms and Signs 1801
Treatment 1802
ANTINEUTROPHILIC CYTOPLASMIC
ANTIBODIES-ASSOCIATED VASCULITIDES:
GRANULOMATOSIS WITH POLYANGIITIS 1802
(FORMERLY KNOWN AS WEGENER’S
GRANULOMATOSIS)
Symptoms and Signs 1803
Treatment 1803
MICROSCOPIC POLYANGIITIS 1803
Treatment 1804
EOSINOPHILIC GRANULOMATOSIS WITH
POLYANGIITIS (FORMERLY KNOWN AS CHURG- 1804
STRAUSS SYNDROME)
Symptoms and Signs 1804
Treatment 1805
RHEUMATOID VASCULITIS 1805
Treatment 1805
LIVEDOID VASCULOPATHY 1805
Treatment 1807
Other Vascular Disorders 1807
ANTIPHOSPHOLIPID SYNDROME 1807
5941
Treatment 1808
WARFARIN (COUMADIN) SKIN NECROSIS 1809
Pathophysiology 1809
Symptoms and Signs 1809
Treatment 1809
COCAINE LEVAMISOLE TOXICITY 1810
CALCINOSIS CUTIS 1811
CALCIPHYLAXIS 1812
Treatment 1813
Ulcers 1813
ISCHEMIC ULCERS 1814
Treatment 1814
VENOUS ULCERS 1815
Treatment 1816
PYODERMA GANGRENOSUM 1817
Painful Infections 1819
NECROTIZING SOFT TISSUE
1819
INFECTION/NECROTIZING FASCIITIS
HERPES ZOSTER 1820
HERPES SIMPLEX 1820
Symptoms and Signs 1820
Diagnosis 1821
Treatment 1821
ERYSIPELAS AND CELLULITIS 1822
Treatment 1823
FURUNCULOSIS AND CARBUNCLE 1824
Treatment 1824
ERYSIPELOID 1825

5942
ERYSIPELOID 1825
Inflammations 1825

PANNICULITIS 1825
Erythema Nodosum 1826
Treatment 1827
DERCUM DISEASE (ADIPOSA DOLOROSA) 1827
Treatment 1828
HIDRADENITIS SUPPURATIVA 1828
Etiology 1829
Symptoms and Signs 1829
Diagnosis 1829
Treatment 1830
INFLAMED EPIDERMAL CYST 1830
BULLOUS DERMATOSES WITH EROSIONS 1832
Stevens-Johnson/Toxic Epidermal Necrolysis Syndrome 1832
Pemphigus Vulgaris 1834
Paraneoplastic Pemphigus 1836
Bullous Pemphigoid 1836
Epidermolysis Bullosa 1838
Disorders of Connective Tissue Structure (Cartilage
1839
Disorders)
RELAPSING POLYCHONDRITIS 1839
Treatment 1840
CHONDRODERMATITIS NODULARIS HELICIS 1841
Neurovascular Cutaneous Disease 1841
SENSORY MONONEUROPATHIES 1841
Treatment 1842
ERYTHROMELALGIA 1842

5943
Symptoms and Signs 1844
Treatment 1844
Other Painful Dermatologic Disorders 1845
CUTANEOUS ENDOMETRIOSIS 1845
PAINFUL NEOPLASMS 1845
ACKNOWLEDGMENTS 1847
CHAPTER 38: Pain Due to Vascular Causes 1860
Basic Neuroanatomic and Neurophysiologic
1860
Considerations
Vascular Pain Syndromes 1863
INTERMITTENT CLAUDICATION 1863
AORTIC AND OTHER LARGE ARTERY PAIN 1869
REST PAIN, ULCERS, AND GANGRENE 1870
PAIN SYNDROMES FOLLOWING STROKE 1872
PAIN ASSOCIATED WITH DISEASES INVOLVING
1873
SMALL ARTERIES
PAIN ASSOCIATED WITH VENOUS DISORDERS 1875
PAIN ASSOCIATED WITH LYMPHATIC DISEASES 1876
PAIN ASSOCIATED WITH AMPUTATION 1876
Differentiating Vascular from Nonvascular Pain 1877
The Relief of Vascular Pain 1878
Conclusion 1882
CHAPTER 39: Pain Due to Thoracic Outlet Syndrome 1885
Anatomy and Pathophysiology 1885
Clinical Presentation: Symptoms and Signs 1887
Diagnostic Tests 1891
Differential Diagnosis 1894
Management 1895

5944
Management 1895
Outcomes 1899
CHAPTER 40: Pain Following Spinal Cord Injury 1902
Extent and Impact of the Problem 1902
Assessment and Classification of Pain Following Spinal
1903
Cord Injury
MUSCULOSKELETAL PAIN 1907
Shoulder Pain 1908
Elbow and Wrist Pain 1909
Back Pain 1909
Muscle Pain Related to Spasticity 1910
VISCERAL PAIN 1910
OTHER NOCICEPTIVE PAIN 1911
AT- AND BELOW-LEVEL SPINAL CORD INJURY
1912
PAIN
OTHER NEUROPATHIC PAIN 1918
PSYCHOSOCIAL ASPECTS OF PAIN AFTER
1919
SPINAL CORD INJURY
Psychological Factors 1919
Social and Environmental Factors 1920
Management of Pain in People with Spinal Cord Injury 1921
NOCICEPTIVE PAIN 1921
Musculoskeletal Pain 1921
Management of Spasticity-Related Pain 1924
VISCERAL PAIN 1926
OTHER NOCICEPTIVE PAIN 1927
OTHER NEUROPATHIC PAIN AND OTHER PAIN 1927
AT- AND BELOW-LEVEL NEUROPATHIC PAIN 1927
Anticonvulsants 1927
5945
Local Anesthetics 1932
N-Methyl-D-Aspartate Receptor Antagonists 1932
Opioids 1933
Cannabinoids 1934
Drug Combinations 1935
Spinal Drug Administration 1935
PSYCHOLOGICAL AND ENVIRONMENTAL
1936
MANAGEMENT
OTHER NONPHARMACOLOGIC MANAGEMENT
1937
OF PAIN IN PEOPLE WITH SPINAL CORD INJURY
Neurostimulation 1938
Massage 1939
Acupuncture 1939
Physical Therapy and Exercise 1939
SURGICAL INTERVENTIONS 1940
Conclusion 1941
PAIN DUE TO CANCER 1953
CHAPTER 41: Epidemiology, Prevalence, and Cancer
1953
Pain Syndromes
Epidemiology of Cancer Pain 1954
PAIN RELATED TO EXTENT OF DISEASE: THE
1955
CANCER DISEASE TRAJECTORY
SPECIAL NEEDS OF PARTICULAR AGE GROUPS:
PEDIATRIC, YOUNG ADULT, ADULT, 1955
GERIATRIC
SPECIAL NEEDS OF PARTICULAR ETHNIC
GROUPS: COMMUNICATION STYLES, COMMON 1957
PREFERENCES, AND MANAGING TABOOS
COMORBIDITIES ASSOCIATED WITH SPECIFIC
CANCERS: LUNG DISEASE, LIVER DISEASE, 1959

5946
COMORBIDITIES ASSOCIATED WITH SPECIFIC
1959
CANCERS: LUNG DISEASE, LIVER DISEASE,
RENAL DISEASE, AND NEUROLOGIC DISEASE
CANCER PAIN AND SUBSTANCE ABUSE 1961
CANCER PAIN IN INMATES 1962
Components of the Comprehensive Medical Evaluation
1963
of a Patient with Chronic Cancer Pain
Pain History 1964
DEFINITION OF PAIN 1964
DEFINITION OF SUFFERING 1965
VALIDATED ASSESSMENT TOOLS 1966
TYPES OF PAIN 1971
PRESENTING COMPLAINT 1973
Pain Onset 1974
Pain Progression 1975
Focality 1976
Symptoms That Accompany Pain 1977
Formulating the Presenting Complaint 1977
DETAILS OF THE PAIN HISTORY 1978
Physical Examination 1982
GENERAL PHYSICAL EXAMINATION 1982
THE REGIONAL PAIN PHYSICAL EXAMINATION 1982
BEDSIDE PROVOCATIVE MANEUVERS 1984
SPECIFIC BEDSIDE PROVOCATIVE MANEUVERS
1986
AND THEIR ROLE IN PAIN DIAGNOSIS
Spurling’s Test 1986
Dermatomal Pain 1987
Sclerotomal Pain 1988
Myotomal Pain 1988

5947
Back Pain 1989
Retroperitoneal Pain Stretch Maneuver 1990
Abdominal Wall Pain 1991
Formulating a Cancer Pain Diagnosis 1992
SYNDROME DIAGNOSIS 1993
PATHOPHYSIOLOGIC DIAGNOSIS 1994
Complementary Clinical Perspectives in the Care of
1995
Cancer Patients
THE MEDICAL MODEL: PAIN IS A
1995
MANIFESTATION OF DISEASE
PALLIATIVE MODEL: PAIN IS BOTH USELESS
1996
AND HARMFUL
REHABILITATIVE (“CHRONIC NONMALIGNANT
PAIN”) MODEL: FOCUS ON DYSFUNCTIONAL
1996
PAIN BEHAVIOR AND PAIN-RELATED
DECONDITIONING
ANESTHETIC MODEL: DIAGNOSTIC AND
1997
THERAPEUTIC BLOCKS
Management of Pain in Specific Clinical Presentations 1998
BONE PAIN 1998
PAIN AND DELIRIUM 1999
PAIN AND NAUSEA 2000
PAIN AND ANOREXIA/CACHEXIA/ASTHENIA 2000
PAIN AND BOWEL DISEASE 2000
MANAGING CANCER PAIN IN THE ADDICT 2001
SAFE PRESCRIBING PRACTICES: UNIVERSAL
2003
PRECAUTIONS
SYMPTOM CLUSTERS 2004
PAIN AT THE END OF LIFE 2005

5948
PAIN AT THE END OF LIFE 2005
CANCER PAIN EMERGENCIES 2006

OPIOID DIVERSION AT THE END OF LIFE 2007

Conclusion 2007
CHAPTER 42: Assessment and Diagnosis of the Cancer
2011
Patient with Pain
Issues in Assessment and Diagnosis of Cancer Pain 2018
Pain and the Cancer Patient 2020
MOLECULAR MECHANISM OF TUMOR PAIN 2023
SOMATIC PAIN 2025
VISCERAL PAIN 2027
NEUROPATHIC PAIN 2029
AFFECTIVE PROCESSING AND SUFFERING 2029
PSYCHOLOGICAL FACTORS AND THE
2031
COMPLEXITIES OF CANCER PAIN
Depression in Cancer Patients 2033
DETECTING AND ASSESSING DEPRESSION IN
2035
THE CANCER PATIENT
Cancer-Related Fatigue 2040
Sleep Disturbance in Cancer 2042
Sources of Pain in the Cancer Patient 2045
Classification of Cancer Pain by Feature 2051
CHRONICITY 2052
INTENSITY/SEVERITY 2053
PATHOPHYSIOLOGY/MECHANISMS 2055
Tumor Involvement of Encapsulated Organs 2055
Tumor Infiltration of Peripheral Nerves 2057
Tumor Infiltration of Soft Tissues 2058

5949
Tumor Infiltration of Abdominal Hollow Organs 2058
Tumor Infiltration and Inflammation of Serous Mucosa 2059
TUMOR TYPE AND STAGE OF DISEASE 2059
Pancreatic Cancer 2060
Ovarian Cancer 2063
Cervical Cancer 2065
Prostate Cancer 2066
Breast Cancer 2069
Lung Cancer 2072
Renal Cell Cancers 2074
Colorectal Cancer 2075
Leukemias and Lymphomas 2076
Multiple Myeloma 2077
Tumor Markers 2078
PATTERNS OF CANCER PAIN 2079
CANCER PAIN SYNDROMES 2081
Bone Metastases 2088
CHARACTERISTICS OF METASTATIC BONE
2093
PAIN
PROGNOSIS 2095
SACRAL INSUFFICIENCY FRACTURES 2097
GRANULOCYTE COLONY-STIMULATING
2100
FACTORS–ASSOCIATED BONE PAIN
Visceral Pain 2100
MECHANISM 2101
VISCERAL PAIN DESCRIPTIONS BY SITE 2104
Neuropathic Pain 2105
NEUROPATHIC PAIN SECONDARY TO CANCER- 2105
RELATED PATHOLOGY IN CRANIAL NERVES

5950
RELATED PATHOLOGY IN CRANIAL NERVES
Cervical Plexopathy 2106
Tumor-Related Mononeuropathy 2107
Radicular Pain/Radiculopathy 2107
Leptomeningeal Metastases 2108
Myelopathies in Cancer 2109
Brachial Plexopathy 2110
Lumbosacral Plexopathy 2113
Tumor Infiltration of the Sacrum and Sacral Nerves 2115
Spinal and Radicular Pain 2115
Central Pain Syndromes Caused by Cancer 2116
Paraneoplastic Peripheral Neuropathy 2116
NEUROPATHIC PAIN SECONDARY TO
2118
THERAPEUTIC INTERVENTIONS
Postsurgical Neuropathic Pain 2119
Radiation Myelopathy, Plexopathy, and Neuropathy 2123
Chemotherapy-Induced Peripheral Neuropathy 2126
ORAL MUCOSITIS 2129
GRAFT-VERSUS-HOST DISEASE 2131
Metastatic Epidural Spinal Cord Compression 2132
MECHANISM 2132
PATTERN OF PAIN 2133
PRESENTATION AND PHYSICAL FINDINGS 2135
INVESTIGATIONS 2136
PROGNOSIS 2137
Stepwise Approach to Pain Assessment 2137
FEATURES OF PAIN HISTORY 2138
Onset 2139
Location 2139

5951
Quality 2139
Timing 2140
Exacerbating/Relieving Factors 2140
Responses to Previous Analgesic and Disease-
2140
Modifying Therapies
Impact of Pain 2140
Effects of Pain on Activities of Daily Living 2141
Psychological State 2143
Familial, Vocational, Social Function 2143
QUALITY OF LIFE ASSESSMENT 2143
GENERAL ASSESSMENT 2145
ASSOCIATED SYMPTOMS 2148
LABORATORY AND IMAGING DATA 2149
PHYSICAL EXAMINATION 2150
DIAGNOSIS 2150
Summary 2150
CHAPTER 43: Cancer Pain: Principles of Management
2175
and Pharmacotherapy
Cancer Pain Management Overview 2180
PRIMARY ANTICANCER TREATMENT 2183
Surgery 2183
Stenting, Drainage Procedures, and Antibiotics 2184
Symptomatic Cancer Pain Management 2186
WORLD HEALTH ORGANIZATION ANALGESIC
2187
LADDER
By Mouth 2190
By the Clock 2190
By the Ladder 2190
For the Individual 2190

5952
For the Individual 2190
With Attention to Detail 2191
Nonsteroidal Anti-Inflammatory Drugs 2191
EFFICACY IN CANCER PAIN 2192
Acetaminophen 2193
Opioid-Induced Bowel Dysfunction 2194
Antiemetics 2198
Adjuvant Analgesics 2202
GENERAL PURPOSE ADJUVANTS 2203
MUSCULOSKELETAL PAIN ADJUVANTS 2204
NEUROPATHIC PAIN ADJUVANTS 2205
BONE PAIN ADJUVANTS 2208
VISCERAL PAIN ADJUVANTS 2209
Psychotropic Drugs 2209
Cannabinoids 2210
Opioid Analgesics 2212
SELECTION OF OPIOID THERAPY IN CANCER
2212
PAIN MANAGEMENT
TOLERANCE AND HYPERALGESIA 2221
MORPHINE 2223
OXYCODONE 2223
OXYMORPHONE 2224
HYDROMORPHONE 2225
METHADONE 2225
LEVORPHANOL 2228
FENTANYL 2229
Transdermal Fentanyl 2230
Oral Transmucosal/Intranasal/Sublingual Fentanyl 2234
Fentanyl-Associated Deaths 2235
5953
CODEINE 2238
TRAMADOL 2239
TAPENTADOL 2240
OPIOIDS NOT RECOMMENDED FOR ROUTINE
2241
USE IN CANCER PAIN CONTROL
OPIOID-RELATED SIDE EFFECTS 2241
Prevention or Minimizing Opioid-Related Side Effects 2241
OPIOID EFFECTS ON COGNITION, MOTOR
2243
SKILLS, AND DRIVING ABILITY
OPIOID ROTATION IN CANCER PAIN 2247
PARENTERAL OPIOID THERAPY 2248
INTRACEREBROVENTRICULAR OPIOIDS 2250
Substance Abuse in Oncology 2252
Home Infusion Therapy 2255
Integrative Oncology 2257
Summary 2259
CHAPTER 44: Interventional Pain Therapies 2283
Intrathecal Drug Therapy 2285
INDICATIONS 2286
INTRATHECAL DRUG DELIVERY SYSTEMS 2286
Simple Percutaneous Intrathecal Catheter 2286
Tunneled Intrathecal Catheter 2286
Implantable Drug Delivery Systems 2287
INTRATHECAL VERSUS EPIDURAL DRUG
2290
DELIVERY
IMPLANTABLE OR EXTERIORIZED
INTRATHECAL DRUG DELIVERY: COST 2291
ANALYSIS

OUTCOME STUDIES 2291

5954
ANALYSIS
OUTCOME STUDIES 2291
PATIENT-CONTROLLED INTRATHECAL
ANALGESIA 2293

PHARMACOLOGY 2294
Opioids 2295
Ziconotide 2295
Local Anesthetics 2296
Clonidine 2297
Other Drugs 2297
CONTRAINDICATIONS AND RISK
2297
MANAGEMENT
COMPLICATIONS AND SIDE EFFECTS 2298
INTRATHECAL THERAPY AND ONGOING
2299
ONCOLOGIC CARE
Spinal Chemoneurolysis 2299
SPINAL CHEMONEUROLYSIS TECHNIQUE 2300
Lumbosacral Neurolysis 2302
Cervical and Thoracic Neurolysis 2302
ADVERSE EFFECTS 2303
CONTRAINDICATIONS 2303
Celiac Plexus Block 2303
INDICATIONS 2303
ANATOMY OF THE CELIAC PLEXUS 2304
GENERAL CONSIDERATIONS 2305
ADVERSE EFFECTS 2305
CELIAC PLEXUS BLOCK TECHNIQUES 2306
Posterior Approach to the Splanchnic Nerves and Celiac
2306
Plexus

5955
OUTCOME STUDIES 2309
Superior Hypogastric Plexus Block 2310
INDICATIONS 2310
ANATOMY OF THE SUPERIOR HYPOGASTRIC
2311
PLEXUS
GENERAL CONSIDERATIONS 2311
ADVERSE EFFECTS 2311
TECHNIQUES 2311
OUTCOME STUDIES 2312
Ganglion of Impar Block 2313
INDICATIONS 2314
ANATOMY OF THE GANGLION OF IMPAR 2314
GENERAL CONSIDERATIONS 2314
ADVERSE EFFECTS 2314
TECHNIQUE 2314
Intercostal Nerve Block 2315
INDICATIONS 2316
ANATOMY OF THE INTERCOSTAL NERVES 2316
GENERAL CONSIDERATIONS 2316
ADVERSE EFFECTS 2316
TECHNIQUE 2317
OUTCOME STUDIES 2319
Blocks of the Head and Neck 2321
Nerve Blocks of the Trigeminal Nerve and Its Branches 2321
INDICATIONS 2321
ANATOMY OF THE TRIGEMINAL NERVE AND
2321
ITS BRANCHES
GENERAL CONSIDERATIONS 2323
ADVERSE EFFECTS 2323

5956
ADVERSE EFFECTS 2323
TECHNIQUES 2323
OUTCOME STUDIES 2327
OTHER HEAD AND NECK INTERVENTIONAL
2327
TARGETS
Spinal Cord Stimulation 2328
Vertebral Augmentation 2329
INDICATIONS 2330
CONTRAINDICATIONS 2331
OUTCOMES 2331
Spinal Cord Ablation 2332
Cordotomy 2333
INDICATIONS 2333
SURGICAL TECHNIQUES 2333
OUTCOMES 2335
COMPLICATIONS 2335
Myelotomy 2336
INDICATIONS 2336
SURGICAL TECHNIQUE 2336
PERCUTANEOUS RADIOFREQUENCY
2336
LESIONING
OPEN LIMITED MYELOTOMY 2337
OUTCOMES 2338
COMPLICATIONS 2338
Dorsal Root Entry Zone Lesioning 2339
IMAGE-GUIDED ABLATION OF PAINFUL BONE
2339
METASTASES
Summary 2340
CHAPTER 45: Pain Caused by Cancer of the Head and
2347
5957
Pain Mechanisms Due to Local and Regional Cancer of 2348
the Head and Neck
TUMOR-INDUCED ALGESIA 2348
Pain Mechanisms Due to Chemotherapy and/or
2351
Radiotherapy
Pain Due to Surgery 2352
Pain Due to Mucositis 2353
EPIDEMIOLOGY 2353
PATHOGENESIS 2355
HEMATOPOIETIC CELL TRANSPLANTATION 2357
HEAD AND NECK RADIATION THERAPY 2358
COMBINED RADIATION THERAPY, SURGERY,
2361
AND/OR CHEMOTHERAPY
Pain Assessment 2362
Management of Oral Mucositis 2362
Pain Management 2364
BASIC ORAL CARE 2364
BLAND ORAL RINSES 2364
TOPICAL ANESTHETICS AND ANALGESICS 2365
TOPICAL ANTIMICROBIALS 2365
SYSTEMIC ANALGESICS 2366
ANTI-INFECTIVE APPROACHES 2367
Hyposalivation 2368
BIOLOGIC RESPONSE MODIFIERS AND
2369
CYTOKINES
COGNITIVE AND BEHAVIORAL
2369
INTERVENTIONS
Conclusion 2370
CHAPTER 46: Cancer-Related Bone Pain 2382

5958
Conclusion 2370
CHAPTER 46: Cancer-Related Bone Pain 2382
Epidemiology Review 2382
PATHOPHYSIOLOGY 2384
EVALUATION OF THE PATIENT WITH BONE
2387
CANCER
Radiography 2387
Bone Scan 2387
Computed Tomography 2387
18F-FDG-PET-CT 2387
Magnetic Resonance Imaging 2388
TREATMENT 2388
CYCLOOXYGENASE-2-SPECIFIC INHIBITORS 2389
CORTICOSTEROIDS 2390
BISPHOSPHONATES 2390
CALCITONIN 2392
OPIOIDS/OPIATE ANTAGONISTS 2392
ADJUVANT ANALGESICS 2393
N-METHYL-D-ASPARTATE ANTAGONISM AND
2393
α2 AGONISTS
HORMONAL THERAPY 2393
RADIONUCLEOTIDES 2394
PROCEDURAL INTERVENTIONS 2394
Intralesional Injection 2395
Percutaneous Vertebroplasty/Kyphoplasty 2395
Rhizotomy 2396
ASSOCIATED PROCESSES 2396
Avascular Necrosis 2396
GRANULOCYTE COLONY-STIMULATING

5959
Conclusion 2397
CHAPTER 47: Cancer-Related Visceral Pain 2402
Epidemiology Review 2402
Characteristics of Visceral Pain 2403
ANATOMY AND PHYSIOLOGY 2403
SENSITIZATION 2407
LOCALIZATION 2408
VISCERAL AFFERENTATION 2410
ASCENDING PATHWAYS 2411
Visceral Pain Syndromes 2412
ORAL MUCOSA 2412
Paraneoplastic Pemphigus 2412
Oropharyngeal Mucositis and Stomatitis 2413
MEDIASTINUM 2413
5-Fluorouracil-Induced Anginal Chest Pain 2413
Pleura 2413
Pancoast Syndrome 2414
PANCREAS 2414
Midline Retroperitoneal Syndrome 2414
Pancreatic Cancer 2415
LIVER PAIN 2415
Hepatic Distension Syndrome 2415
INTESTINAL PAIN 2416
Chronic Intestinal Obstruction 2416
Peritoneal Carcinomatosis 2416
Radiation Enteritis 2417
Intraperitoneal Chemotherapy Pain 2417
PELVIC PAIN 2417
Malignant Perineal Pain 2417
5960
Malignant Perineal Pain 2417
Ureteral Obstruction 2418
Ovarian Cancer Pain 2418
Tumor-Related Gynecomastia 2418
Intravesical Chemotherapy or Immunotherapy 2419
Corticosteroid-Induced Perineal Discomfort 2419
ADRENAL PAIN SYNDROME 2419
Vascular Obstruction 2419
Venous Thrombosis 2420
Superior Vena Cava Obstruction 2420
Acute Mesenteric Vein Thrombosis 2421
PAIN SYNDROMES RELATED TO INTRAVENOUS
2421
CHEMOTHERAPEUTIC AGENTS
Hepatic Artery Infusion Pain 2421
COMPLEX VISCERAL PAIN SYNDROMES 2421
POSTRADIATION VISCERAL PAIN 2422
Radiation Enteritis and Proctitis 2422
Burning Perineum Syndrome 2422
Radiation Cystitis 2423
POSTCHEMOTHERAPY VISCERAL PAIN 2423
Treatment 2423
N-METHYL-D-ASPARTATE RECEPTOR
2424
ANTAGONISTS
CORTICOSTEROIDS 2424
GABAPENTIN 2424
SHORT INTERFERING RNA THERAPEUTICS 2424
T-TYPE CALCIUM CHANNEL ANTAGONISTS 2425
AMPA/KAINATE ANTAGONISTS 2426
P38 KINASE INHIBITORS 2426

5961
P2X PURINOCEPTOR 3 ANTAGONISTS 2427
NEWER OPIOID DERIVATIVES FOR THE
2429
TREATMENT OF CHRONIC PAIN
Cebranopadol 2429
PROCEDURAL INTERVENTIONS 2430
Ganglion Impar Block 2430
Thoracic Sympathetic Ganglion Block 2430
Interpleural Catheters 2431
Surgery 2432
Dorsal Myelotomy for Treatment of Intractable Visceral
2434
Cancer Pain
Hypophysectomy and Cancer Pain 2434
Conclusion 2435
CHAPTER 48: Radiotherapy and Chemotherapy in
2442
Cancer Pain Management
Introduction 2442
BONE DISEASE 2449
CLINICAL APPLICATIONS OF RADIATION
2450
THERAPY
Response of Tumors to Radiotherapy 2452
TRACHEA, BRONCHI, AND LUNGS 2452
PANCREATIC CANCER 2453
PELVIS 2453
SKIN AND SUBCUTANEOUS TISSUES 2455
BRAIN METASTASES 2455
Bone Metastases 2456
Single-Fraction Radiation 2459
Stereotactic Radiation for Nonspine Bone Metastases 2462
Reirradiation 2463

5962
Single-Fraction Radiation 2459
Stereotactic Radiation for Nonspine Bone Metastases 2462
Reirradiation 2463
Pathologic Fracture 2465
Spinal Cord Compression 2468
RADIATION TOLERANCE OF THE SPINAL CORD 2477
CLINICAL MANAGEMENT 2478
Treatment of Diffuse Bone Metastases 2480
WIDE-FIELD RADIOTHERAPY 2481
RADIOPHARMACEUTICALS 2482
Role of Palliative Chemotherapy 2486
CLINICAL APPLICATIONS 2491
PALLIATIVE CHEMOTHERAPY 2491
LYMPHOMA 2492
BREAST CANCER 2492
HEAD AND NECK CANCER 2494
OVARIAN CANCER 2494
LUNG CANCER 2495
GASTROINTESTINAL CANCERS 2495
PROSTATE CANCER 2496
DECISION MAKING ABOUT CHEMOTHERAPY 2497
SIDE EFFECTS AND COMPLICATIONS 2499
Endocrine Therapy 2499
ENDOCRINE THERAPY FOR RELIEF OF CANCER
2500
PAIN
Bisphosphonates 2501
Summary 2501
CHAPTER 49: Cancer Pain in Children 2516
Overview of Childhood Cancer 2516
5963
TREATMENT 2517
SURVIVORSHIP 2517
Pain in Children: How Does This Differ from That in
2517
Adults?
INFANTS–PRESCHOOL 2518
SCHOOL AGE–ADOLESCENCE 2519
Pediatric Cancer Pain 2519
EPIDEMIOLOGY OF PEDIATRIC CANCER PAIN 2520
UNDERTREATMENT AND IMPACT OF
2521
PEDIATRIC CANCER PAIN
Evaluation of Pediatric Cancer Pain 2522
HISTORY AND PHYSICAL EXAM 2523
SENSORY EXPERIENCE—SELF-REPORT 2524
SENSORY EXPERIENCE—OBSERVATION 2524
EMOTIONAL AND COGNITIVE EXPERIENCE 2525
FUNCTIONAL AND QUALITY OF LIFE
2526
ASSESSMENT
PAST PAIN-DIRECTED THERAPIES 2527
CANCER HISTORY—DIAGNOSIS 2527
CANCER HISTORY—TREATMENTS 2529
PAST MEDICAL, PSYCHIATRIC, SOCIAL, AND
2530
SPIRITUAL HISTORY
PROXY REPORTS 2530
INTEGRATING DATA IN EVALUATION OF THE
2531
WHOLE CHILD
INCORPORATING TECHNOLOGY INTO
2532
ASSESSMENT
Etiologies of Cancer Pain 2532
DISEASE-RELATED PAIN 2533

5964
DISEASE-RELATED PAIN 2533
Bone Marrow Infiltration 2533
Brain and Spinal Tumors 2533
Visceral Pain 2535
Bone Tumors 2535
PROCEDURE-RELATED PAIN 2536
Postlumbar Puncture Headache 2539
Postoperative Pain 2540
Phantom Limb Pain 2541
TREATMENT-RELATED PAIN 2542
Bone Marrow Expansion 2542
Mucositis 2542
Neuropathic Pain 2545
PAIN FROM OTHER ETIOLOGIES 2546
Infection 2546
Graft-versus-host Disease 2547
Bone Complications of Therapy 2548
PAIN IN SURVIVORSHIP 2548
Management of Pain 2549
Pharmacologic Management of Cancer-Related Pain in
2550
Children
Overview of Opioid Analgesia in Children 2552
ADVERSE EFFECTS 2553
DEPENDENCE AND ADDICTION 2554
TOLERANCE TO OPIOIDS 2554
“WEAK” OPIOID 2555
ADJUVANT THERAPIES FOR NEUROPATHIC
2555
PAIN
Physical and Psychological Therapies for Pain in the

5965
HYPNOTHERAPY 2558
EXPRESSIVE ARTS THERAPIES 2559
MASSAGE 2560
BIOFEEDBACK 2561
BOTANICALS 2562
CANNABIS 2563
MAGNETS 2564
SPIRITUALITY/RELIGIOSITY 2564
THERAPEUTIC YOGA 2565
Palliative Care for Children with Cancer 2566
Summary 2567
ACUTE PAIN 2583
CHAPTER 50: Acute Pain Management in Children 2583
Pain Assessment in Infants and Children 2584
Analgesic Pharmacology in Infants and Children 2587
Nonopioid Analgesics 2587
ONTOGENY OF PROSTANOID BIOSYNTHESIS
2588
AND CYCLO-OXYGENASES
ASPIRIN AND OTHER SALICYLATES 2588
ACETAMINOPHEN 2588
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS 2589
KETAMINE 2592
ANTICONVULSANTS 2593
Opioids 2593
ONTOGENY OF OPIOID ACTIONS 2594
CODEINE 2595

TRAMADOL 2596
OXYCODONE 2596

5966
CODEINE 2595
TRAMADOL 2596
OXYCODONE 2596
MORPHINE 2597

HYDROMORPHONE 2599
METHADONE 2600
FENTANYL 2601
MEPERIDINE 2603
Opioid Administration in Infants and Children 2603
INTERMITTENT INTRAVENOUS BOLUS DOSING 2604
CONTINUOUS OPIOID INFUSIONS 2605
PATIENT-, NURSE-, AND PARENT-CONTROLLED
2605
ANALGESIA
TREATMENT OF OPIOID SIDE EFFECTS 2607
LOCAL ANESTHETICS AND REGIONAL
2610
ANESTHESIA IN INFANTS AND CHILDREN
CUTANEOUS ANALGESIA 2611
WOUND INFILTRATION 2611
Epidural Analgesia in Infants and Children 2611
DRUGS AND DRUG DOSING USED FOR
2613
EPIDURAL ANALGESIA
Peripheral Nerve Blocks in Children 2617
SUPRACLAVICULAR 2619
INFRACLAVICULAR 2619
SCIATIC NERVE BLOCK 2620
Sciatic-Subgluteal Approach 2620
Popliteal Approach 2621
FEMORAL BLOCK 2622

5967
PAIN ASSOCIATED WITH SICKLE CELL 2626
VASOOCCLUSIVE EPISODES
CHILDREN WITH TRAUMA 2626
CHILDREN WITH DEVELOPMENTAL
2627
DISABILITIES
Conclusions 2627
CHAPTER 51: Acute Pain in Adults 2637
Acute and Chronic Effects of Acute Pain 2638
Neurobiology of Acute Pain 2640
PRIMARY AFFERENTS AND PERIPHERAL
2640
NERVE NEUROTRANSMITTERS
SPINAL CORD AND SUPRASPINAL STRUCTURES 2641
Prevention 2642
PREVENTIVE ANALGESIA 2642
Treatment Methods 2644
SYSTEMIC ANALGESIC TECHNIQUES 2645
Opioids 2645
Nonsteroidal Anti-inflammatory Agents 2648
Excitatory Amino Acids 2652
Anticonvulsants 2653
α-Adrenergic Medications 2654
Steroids 2655
Serotoninergic Medications 2656
NONSELECTIVE NORADRENERGIC AND
2656
SEROTONINERGIC MEDICATIONS
INTRAVENOUS PATIENT-CONTROLLED 2658
ANALGESIA
REGIONAL ANALGESIC TECHNIQUES 2661
Single-Dose Neuraxial Opioids 2661

5968
REGIONAL ANALGESIC TECHNIQUES 2661
Single-Dose Neuraxial Opioids 2661
Continuous Epidural Analgesia 2663

PERIPHERAL REGIONAL ANALGESIA 2673

Intra-articular Analgesia 2675
ENHANCED RECOVERY AFTER SURGERY
2676
PATHWAYS
Analgesia in Special Populations 2677
WAR TRAUMA 2677
AMBULATORY SURGICAL PATIENTS 2681
ELDERLY PATIENTS 2682
OPIOID-TOLERANT PATIENTS 2684
OBESITY, OBSTRUCTIVE SLEEP APNEA, AND
2688
SLEEP
Gender or Sex Differences in Analgesia 2690
Inpatient Pain Services 2695
Long-term Impact of Acute Pain 2696
CHAPTER 52: Regional Anesthesia Techniques for
2714
Acute Pain Management
Continuous Epidural Analgesia 2714
THORACIC EPIDURAL ANALGESIA 2715
BLOCK TECHNIQUE: EPIDURAL 2717
Subarachnoid/Intrathecal Analgesia 2718
TECHNIQUE 2718
CLINICAL SUBARACHNOID ANALGESIA 2720
Opioids 2720
Clonidine 2721
Combined Spinal and Epidural 2721
TECHNIQUE OF COMBINED SPINAL EPIDURAL 2722
5969
Contraindications of Neuraxial Techniques 2723
SEPSIS, FEVER, AND VIRAL INFECTIONS 2724
COAGULOPATHY, THROMBOCYTOPENIA, AND
2724
BLEEDING DISORDERS
CENTRAL NERVOUS SYSTEM DISORDERS 2725
Analgesic Adjuvants for Central and Peripheral
2726
Analgesia
INTRODUCTION 2726
NEURAXIAL OPIOIDS 2727
PERINEURAL OPIOIDS 2727
PERINEURAL CLONIDINE AND
2728
DEXMEDETOMIDINE
PERINEURAL DEXAMETHASONE 2729
Transversus Abdominis Plane Block, Ilioinguinal
2730
Iliohypogastric Block, Rectus Sheath Block
TRANSVERSUS ABDOMINIS PLANE BLOCK 2730
Landmark Technique 2730
Ultrasound-Guided Transversus Abdominis Plane 2731
ILIOHYPOGASTRIC AND ILIOINGUINAL BLOCK 2732
RECTUS SHEATH BLOCK 2733
Peripheral Nerve Blocks and Catheters 2734
Interscalene Block 2736
INDICATIONS 2736
LANDMARKS 2736
TECHNIQUES 2736
Nerve Stimulation 2736
Ultrasound Guidance 2737
CLINICAL EFFECTS 2738
Supraclavicular Block 2739

5970
Nerve Stimulation 2736
Ultrasound Guidance 2737
CLINICAL EFFECTS 2738
Supraclavicular Block 2739
INDICATIONS 2739

LANDMARKS 2740
ULTRASOUND TECHNIQUE 2740
CLINICAL EFFECTS 2741
Infraclavicular Block 2742
INDICATIONS 2742
LANDMARKS 2742
TECHNIQUE 2743
CLINICAL EFFECTS 2744
Axillary Block 2745
INDICATIONS 2745
LANDMARKS 2745
TECHNIQUES 2746
Nerve Stimulation 2746
Transarterial Technique 2746
Ultrasound Guidance 2746
CLINICAL EFFECTS 2748
Suprascapular and Axillary Nerve Block 2748
INDICATIONS 2748
LANDMARKS 2748
ULTRASOUND TECHNIQUE 2748
Axillary Nerve Block 2749
CLINICAL EFFECTS 2750
Brachial Plexus Terminal Branch Blocks at the Elbow
2750

5971
TECHNIQUES 2751
Nerve Stimulation 2751
Ultrasound Guidance 2751
CLINICAL EFFECTS 2754
Paravertebral Nerve Block 2755
INDICATIONS AND LANDMARKS 2755
TECHNIQUES 2755
Landmark Technique 2756
Ultrasound Technique 2756
CONTRAINDICATIONS 2758
CLINICAL EFFECTS 2758
Nerve Blocks of the Lumbar Plexus 2759
INDICATIONS AND LANDMARKS 2759
TECHNIQUES 2760
Landmark Technique 2760
Ultrasound Guidance 2762
COMPLICATIONS 2763
CLINICAL EFFECTS 2764
Femoral Block 2764
INDICATIONS 2764
LANDMARKS 2765
TECHNIQUES 2765
Nerve Stimulator-Guided Femoral Block 2765
Ultrasound Technique 2766
COMPLICATIONS 2767
CLINICAL EFFECTS 2767
Adductor Canal Block 2768

INDICATIONS 2768

5972
Adductor Canal Block 2768
INDICATIONS 2768
CLINICAL EFFECTS 2771
TECHNIQUE 2771
Ultrasound Guidance 2771
Landmark Approach 2772
COMPLICATIONS 2773
Fascia Iliaca Block 2773
INDICATIONS 2773
TECHNIQUES 2774
Landmark Approach 2774
Ultrasound Guidance 2774
CLINICAL EFFECTS 2776
COMPLICATIONS 2777
Lateral Femoral Cutaneous Nerve Block 2777
INDICATIONS AND LANDMARKS 2777
TECHNIQUES 2778
Landmark Technique 2778
Ultrasound Guidance 2778
CLINICAL EFFECTS 2779
COMPLICATIONS 2779
Obturator Nerve 2779
INDICATIONS AND LANDMARKS 2780
TECHNIQUES 2780
Landmark Technique 2780
Ultrasound Guidance 2781
COMPLICATIONS 2782
Sacral Plexus-Sciatic Nerve Block 2782

5973
TECHNIQUES 2783
Landmark Technique 2783
Ultrasound Technique 2787
CLINICAL EFFECTS 2790
COMPLICATIONS 2791
Ankle Block 2791
INDICATIONS 2791
TECHNIQUES 2791
Landmark Technique 2792
Classic Ultrasound Technique 2793
CLINICAL EFFECTS 2794
COMPLICATIONS 2795
Quadratus Lumborum Block 2795
INDICATIONS 2795
ULTRASOUND TECHNIQUE 2797
Quadratus Lumborum 1 2797
CLINICAL EFFECTS 2798
COMPLICATIONS 2798
PECS/Serratus Anterior Plane Block 2799
INDICATIONS 2799
ULTRASOUND TECHNIQUE 2800
PECS I and PECS II 2800
Serratus Anterior Plane Block 2801
CLINICAL EFFECTS 2802
COMPLICATIONS 2802
Complications of Peripheral Nerve Blocks 2802
NEUROLOGIC COMPLICATIONS 2803

POSTSURGICAL INFLAMMATORY
2805

5974
COMPLICATIONS 2802
Complications of Peripheral Nerve Blocks 2802
NEUROLOGIC COMPLICATIONS 2803
POSTSURGICAL INFLAMMATORY
NEUROPATHY 2805

NONNEUROLOGIC COMPLICATIONS 2805

SUMMARY OF TREATMENT OF LOCAL
2806
ANESTHETIC SYSTEMIC TOXICITY
Summary 2808
CHAPTER 53: Burn Pain 2832
The Nature of Burn Pain 2833
Psychological Factors 2837
Generalized Treatment Paradigm for Burn Pain 2840
Pharmacologic Approaches 2845
OPIOIDS 2845
NONOPIOIDS 2847
ANXIOLYTICS 2848
ANESTHETICS 2848
PHARMACOLOGIC OPTIONS FOR
2850
BACKGROUND PAIN MANAGEMENT
PHARMACOLOGIC OPTIONS FOR PROCEDURAL
2851
PAIN MANAGEMENT
PHARMACOLOGIC OPTIONS FOR
2852
POSTOPERATIVE PAIN MANAGEMENT
Nonpharmacologic Approaches 2852
COGNITIVE INTERVENTIONS AND COPING
2852
STYLES
PREPARATORY INFORMATION 2854
BEHAVIORAL INTERVENTIONS 2855

5975
Conclusion 2860
ACKNOWLEDGMENT 2861
PAIN IN SPECIAL POPULATIONS 2868
CHAPTER 54: Persistent Pain in Children 2868
Epidemiology of Chronic Pain in Children 2868
MUSCULOSKELETAL PAIN 2869
Arthritis 2870
Nonrheumatologic Musculoskeletal Pain 2870
Fibromyalgia Syndrome 2871
Complex Regional Pain Syndrome 2872
Back Pain 2872
Temporomandibular Disorders 2873
HEADACHE 2873
CHRONIC ABDOMINAL PAIN 2874
DISEASE- OR TREATMENT-RELATED PAIN 2875
Sickle Cell Disease 2875
Cystic Fibrosis 2876
Phantom Limb 2876
ADDITIONAL CONSIDERATIONS 2876
Impact of Persistent Pain on Children and Families 2877
Clinical Evaluation of the Child with Chronic Pain 2880
BACKGROUND 2880
HISTORY 2882
MEASUREMENT OF PAIN AND FUNCTIONING 2884
PHYSICAL EVALUATION 2889
CLINICAL FORMULATION 2889
FEEDBACK WITH THE FAMILY 2890
Treatment 2892
GENERAL PRINCIPLES OF TREATMENT 2892

5976
Treatment 2892
GENERAL PRINCIPLES OF TREATMENT 2892
SPECIFIC INTERVENTIONS FOR
2894
CHRONIC/PERSISTENT PAIN
Pharmacologic Interventions 2894
Psychological Interventions 2899
School and Social Reintegration 2902
Sleep 2905
Intensive Rehabilitation Therapy 2907
Specific Entities 2908
MUSCULOSKELETAL PAIN 2908
COMPLEX REGIONAL PAIN SYNDROMES 2909
BACK PAIN 2911
HEADACHE 2912
FUNCTIONAL GASTROINTESTINAL PAIN 2915
Barriers to Care 2916
Conclusion 2917
CHAPTER 55: Pain in the Older Person 2933
Overview 2933
THE PREVALENCE OF PAIN IN OLDER ADULTS 2933
Pain in the Older Person 2934
IMPACT OF PAIN ON FUNCTIONING AND
2934
QUALITY OF LIFE
UNDERTREATMENT OF PAIN IN OLDER
2935
PERSONS
CHANGE IN PAIN PROCESSING AND
2936
MODULATION
Assessment of Pain in the Older Person 2937
CLINICAL EVALUATION OF PAIN 2937

5977
Pharmacologic Treatment of Pain in Older Persons 2940
PHARMACOKINETICS AND
PHARMACODYNAMICS ASSOCIATED WITH 2940
AGING
SAFE, EFFECTIVE USE OF NONOPIOIDS IN THE
2941
OLDER PERSON
Acetaminophen 2941
Nonsteroidal Anti-inflammatory Drugs 2942
Safe Nonsteroidal Anti-inflammatory Drug Product
2943
Selection and Monitoring Use
SAFE, EFFECTIVE USE OF OPIOIDS IN THE
OLDER PERSON POTENTIAL RISKS OF OPIOID 2944
ANALGESICS
Potential Safety Concerns with Opioids 2945
Prudent Product Selection and Use 2946
SAFE, EFFECTIVE USE OF ADJUVANTS IN THE
2948
OLDER PERSON
Additional Treatments for Pain of Older Person 2950
INTERVENTIONAL APPROACHES 2950
PHYSICAL MODALITIES 2951
PSYCHOSOCIAL MODALITIES 2952
COMPLEMENTARY AND INTEGRATIVE HEALTH 2953
MULTIDISCIPLINARY PAIN TREATMENTS 2954
Summary 2955
CHAPTER 56: Obstetric Pain 2967
Historical Notes 2967
Pain of Childbirth 2968
CHILDBIRTH PAIN MECHANISMS AND 2970
PATHWAYS
FACTORS THAT AFFECT THE PAIN OF
5978
PATHWAYS
FACTORS THAT AFFECT THE PAIN OF 2973
CHILDBIRTH
EFFECTS OF PAIN ON THE MOTHER AND FETUS 2973
Physiologic Changes of Pregnancy 2976
RESPIRATORY CHANGES 2977
CARDIOVASCULAR CHANGES 2978
Aortocaval Compression 2979
Implications for Labor Analgesia 2980
CENTRAL NERVOUS SYSTEM CHANGES 2981
Anatomy of the Spinal Column and Analgesic
2981
Implications
Neurohormonal Changes and Analgesic Implications 2982
PHARMACOKINETIC CHANGES 2982
UTEROPLACENTAL UNIT 2982
Transfer of Drugs across the Placenta 2983
Nonpharmacologic Methods of Labor Analgesia 2984
ANTENATAL CHILDBIRTH EDUCATION 2984
LABOR SUPPORT 2984
HYDROTHERAPY 2985
INTRADERMAL WATER INJECTIONS 2985
HYPNOSIS 2986
TRANSCUTANEOUS ELECTRICAL
2986
STIMULATION
ACUPUNCTURE AND ACUPRESSURE 2986
Systemic Analgesia 2986
INHALATIONAL ANALGESIA 2987
PARENTERAL OPIOID ANALGESIA 2987
Patient-Controlled Intravenous Analgesia 2988

5979
Drugs for Initiation of Epidural Analgesia 2991
COMBINED SPINAL-EPIDURAL ANALGESIA 2993
Drugs for Initiation of Combined Spinal-Epidural
2995
Analgesia
MAINTENANCE OF EPIDURAL ANALGESIA 2996
OTHER CENTRAL NEURAXIAL TECHNIQUES 2998
Single-Shot and Continuous Spinal Analgesia 2998
Dural Puncture Epidural Analgesia 2998
Caudal Analgesia 2999
SIDE EFFECTS OF NEURAXIAL ANALGESIA 2999
Hypotension 2999
Pruritus 3000
Fetal Bradycardia 3000
Maternal Hyperthermia 3000
COMPLICATIONS OF NEURAXIAL ANALGESIA 3001
Unintentional Dural Puncture 3001
Respiratory Depression 3001
Other Regional Analgesic Techniques 3002
PARACERVICAL BLOCK 3002
LUMBAR SYMPATHETIC BLOCK 3002
PUDENDAL BLOCK 3003
PERINEAL INFILTRATION 3003
Effects of Analgesia on the Progress of Labor 3003
Nonobstetric Drug Therapy during Pregnancy and
3004
Lactation
DRUG CLASSIFICATION DURING PREGNANCY
3006
AND LACTATION
Analgesic Drugs during Pregnancy and Lactation 3006
CHAPTER 57: Pain and Sickle Cell Disease 3014
5980
DRUG CLASSIFICATION DURING PREGNANCY 3006
AND LACTATION
Analgesic Drugs during Pregnancy and Lactation 3006
CHAPTER 57: Pain and Sickle Cell Disease 3014
Introduction 3014
HISTORY 3014
NATURE OF THE SICKLE MUTATION 3016
CLASSIFICATION OF SICKLE CELL SYNDROMES 3016
GENOTYPES 3018
Pathophysiology 3019
VASO-OCCLUSION 3020
CELLULAR DEHYDRATION 3023
ADHESION TO VASCULAR ENDOTHELIUM 3024
INFLAMMATION AND REPERFUSION INJURY 3024
GENETIC MARKERS 3025
OTHER FACTORS 3027
Classification of Sickle Cell Pain Syndromes 3028
Acute Sickle Cell Pain Syndromes 3030
THE VASCULAR OCCLUSIVE CRISIS 3030
Predisposing Factors 3031
Precipitating Factors 3032
Phases of the Acute Vaso-occlusive Crisis 3033
The Prodromal Phase 3035
The Initial Phase 3036
The Established Phase 3036
The Resolving Phase 3037
The Relapsing or Postdromal Phase 3037
ACUTE CHEST SYNDROME 3041
ACUTE ABDOMINAL PAIN SYNDROMES 3047

5981
HAND–FOOT SYNDROME (DACTYLITIS) 3055
PRIAPISM 3055
ACUTE MULTIORGAN FAILURE 3059
Chronic Sickle Cell Pain 3059
AVASCULAR NECROSIS 3059
LEG ULCERS 3063
INTRACTABLE PAINFUL EPISODES 3067
NEUROPATHIC PAIN 3067
Management of Sickle Cell Pain 3068
NONPHARMACOLOGIC MANAGEMENT OF PAIN 3069
PHARMACOLOGIC MANAGEMENT OF PAIN 3070
Nonopioids and Sickle Cell Disease 3070
Opioids and Sickle Cell Disease 3071
Adjuvants and Sickle Cell Disease 3071
Management of Pain at Home 3072
Outpatient Management of Sickle Cell Pain 3073
Pain Management in the Day Unit 3074
Pain Management in the Emergency Department 3075
Management of Sickle Cell Pain in the Hospital 3075
Specific Approaches to Treatment 3077
Preventive Therapies 3078
Induction of Fetal Hemoglobin 3078
Hydroxyurea 3079
Hydroxyurea and the HUG Trials 3080
Benefits and Side Effects of Hydroxyurea 3081
Other Novel Approaches to Therapy 3083
CURATIVE THERAPIES 3084
Allogeneic Hematopoietic Stem Cell Transplant 3084
Gene Therapy 3085
5982
CURATIVE THERAPIES 3084
Allogeneic Hematopoietic Stem Cell Transplant 3084
Gene Therapy 3085
Conclusion 3087
CHAPTER 58: Pain in HIV 3106
Prevalence of Pain in HIV/AIDS 3107
Pain in Women with HIV/AIDS 3108
Pain in Children with HIV/AIDS 3108
Specific Pain Syndromes in HIV/AIDS 3109
GASTROINTESTINAL PAIN 3109
OROPHARYNGEAL PAIN 3109
ESOPHAGEAL PAIN 3110
ABDOMINAL PAIN 3110
ANORECTAL 3112
Chest Pain Syndromes 3112
CARDIAC PAIN 3113
PULMONARY/PLEURITIC PAIN 3113
CHEST WALL PAIN 3114
Musculoskeletal Pain 3114
ARTHROPATHY 3114
OSTEOPOROSIS 3115
Neurologic Manifestations 3115
PERIPHERAL NEUROPATHY 3115
DISTAL SYMMETRIC POLYNEUROPATHY 3117
TREATMENT OF HIV-ASSOCIATED SENSORY
3118
NEUROPATHY
INFLAMMATORY DEMYELINATING
3119
POLYNEUROPATHY
MONONEURITIS MULTIPLEX 3120

5983
Headache 3121
PRIMARY HEADACHES 3121
SECONDARY HEADACHES 3125
Management of Pain 3127
EVALUATION GUIDELINES 3127
PAIN MEASUREMENT/ASSESSMENT TOOLS 3127
MULTIMODAL TREATMENT APPROACH 3128
PHARMACOLOGIC TREATMENT 3128
Acetaminophen 3133
Nonsteroidal Anti-inflammatory Drugs 3133
Opioid Analgesics 3134
Antidepressant Agents 3136
Anticonvulsants 3138
Topical Capsaicin 3139
Cannabinoids 3140
Recombinant Human Nerve Growth Factor 3140
Combination Pharmacotherapy 3140
NONPHARMACOLOGIC THERAPIES 3141
UNDERTREATMENT OF PAIN 3142
BARRIERS TO PAIN MANAGEMENT 3143
Summary 3143
CHAPTER 59: The Treatment of Chronic Pain in
3153
Patients with History of Substance Abuse
Principle of Balance 3155
THE IMPORTANCE OF THE DEFINITIONS 3156
Basic Science of the Disease of Addiction 3158
BINARY CONCEPT OF PAIN AND ADDICTION 3161
PAIN AND OPIOID ADDICTION—A CONTINUUM
APPROACH 3163

5984
BINARY CONCEPT OF PAIN AND ADDICTION 3161
PAIN AND OPIOID ADDICTION—A CONTINUUM
3163
APPROACH
SEPARATING THE “MOTIVE” FROM
“BEHAVIOR” WHEN DEALING WITH PAIN AND 3164
ADDICTION
OPIOIDS FOR ANALGESIA OR OPIOID-
3166
STABILIZING EFFECT?
Recommendations for Terminating Opioid Therapy 3167
Assessment Tools 3169
Universal Precautions in Pain Medicine 3171
THE 10 PRINCIPLES OF UNIVERSAL
3172
PRECAUTIONS IN PAIN MEDICINE
PATIENT TRIAGE 3176
Treating the Pain Patient on Opioid Agonist Treatment 3177
The Treatment of Pain and Suffering in Our Society 3179
Conclusion 3181
CHAPTER 60: Compliance Monitoring in Chronic Pain
3186
Management
How Communication Influences Compliance
3186
Assessment
Interpreting Aberrant Behavior 3189
POTENTIAL TREATMENT TRAPS IN
3190
COMPLIANCE MONITORING
Borrowing from Tomorrow to Pay for Today 3190
Avoiding Excessive Pill Loads 3191
Using Pill Load Limits to Modify Behavior 3193
Compliance Monitoring Tips and Traps 3193
Urine Drug Testing in Pain Medicine 3194
SPECIMEN CHOICE 3195
5985
FREQUENCY OF TESTING 3196
TESTING STRATEGIES 3196
PRESUMPTIVE VERSUS DEFINITIVE TESTING 3198
LIMITATIONS OF TEST INTERPRETATION 3200
Dealing with Unexpected Urine Toxicology Results 3201
Decision to Terminate Opioid Therapy 3202
FUTURE CONSIDERATIONS 3204
VISCERAL PAIN 3209
CHAPTER 61: Headache 3209
General Principles 3209
PRIMARY HEADACHE SYNDROMES 3210
ANATOMY AND PHYSIOLOGY 3210
SECONDARY HEADACHE 3213
MIGRAINE 3215
Clinical Features 3215
Frequent Migraine 3216
Principles of Management of Migraine 3217
Nonpharmacologic Management of Migraine 3218
Preventive Treatments of Migraine 3218
Acute Attack Therapies of Migraine 3220
Medication Overuse 3224
TENSION-TYPE HEADACHE 3225
Clinical Features 3225
Pathophysiology 3225
Management 3226
TRIGEMINAL-AUTONOMIC CEPHALALGIAS 3226
Cluster Headache 3226
Managing Cluster Headache 3229
PAROXYSMAL HEMICRANIA 3231

5986
TRIGEMINAL-AUTONOMIC CEPHALALGIAS 3226
Cluster Headache 3226
Managing Cluster Headache 3229
PAROXYSMAL HEMICRANIA 3231
SHORT-LASTING UNILATERAL NEURALGIFORM
HEADACHE ATTACKS WITH CONJUNCTIVAL
3232
INJECTION AND TEARING OR CRANIAL
AUTONOMIC ACTIVATION
OTHER PRIMARY HEADACHES 3233
Primary Stabbing Headache 3233
Primary Cough Headache 3234
Primary Exertional Headache 3234
Primary Sex Headache 3235
Hypnic Headache 3236
Primary Thunderclap Headache 3237
Hemicrania Continua 3238
New Daily Persistent Headache 3239
Low Cerebrospinal Fluid Volume Headache 3240
Raised Cerebrospinal Fluid Pressure Headache 3243
Posttraumatic Headache 3244
OTHER IMPORTANT FORMS OF SECONDARY
3244
HEADACHE
Giant Cell Arteritis 3244
Cervicogenic Headache 3245
ACKNOWLEDGMENT 3245
CHAPTER 62: Noncardiac Chest Pain 3253
Epidemiology 3256
Natural History 3259
Pathophysiology 3260

5987
SUSTAINED ESOPHAGEAL CONTRACTIONS 3267
ESOPHAGEAL HYPERSENSITIVITY 3268
ALTERED AUTONOMIC ACTIVITY 3273
PSYCHOLOGICAL COMORBIDITY 3273
Diagnosis of Noncardiac Chest Pain 3276
CARDIOLOGY EVALUATION 3276
GERD-RELATED NCCP 3277
BARIUM ESOPHAGRAM 3277
UPPER ENDOSCOPY 3278
AMBULATORY 24-HOUR ESOPHAGEAL pH
3280
MONITORING
THE WIRELESS pH SYSTEM 3281
THE PROTON PUMP INHIBITOR TEST 3283
MULTICHANNEL INTRALUMINAL IMPEDANCE 3287
ESOPHAGEAL DYSMOTILITY 3288
ESOPHAGEAL MANOMETRY 3288
PROVOCATIVE TESTING 3290
EDROPHONIUM (TENSILON) TEST 3290
ERGONOVINE STIMULATION TEST 3291
PENTAGASTRIN STIMULATION TEST 3291
Sensory Testing of the Esophagus 3291
ACID PERFUSION TEST (BERNSTEIN TEST) 3295
ELECTRICAL STIMULATION 3296
INTRALUMINAL ULTRASONOGRAPHY 3297
BALLOON DISTENSION 3298
ESOPHAGEAL EVOKED POTENTIALS 3303

BRAIN IMAGING 3304

SENSORY TESTING—PITFALLS IN STUDY
3305

5988
SENSORY TESTING—PITFALLS IN STUDY
DESIGN 3305

PSYCHOLOGICAL EVALUATION 3306

Treatment 3307
GERD-RELATED NCCP 3307
NON–GERD-RELATED NCCP 3310
PAIN MODULATORS 3313
Trazodone 3315
Serotonin Norepinephrine Reuptake Inhibitors 3315
Selective Serotonin Reuptake Inhibitors 3316
Adenosine Antagonists 3317
Octreotide 3318
Benzodiazepines 3319
ENDOSCOPIC TREATMENT AND SURGERY FOR
3319
NCCP
JOHREI THERAPY 3321
PSYCHOLOGICAL TREATMENT 3321
FUTURE THERAPY 3323
CHAPTER 63: Abdominal, Peritoneal, and
3341
Retroperitoneal Pain
Clinical Approach to Abdominal Pain 3342
PAIN LOCALIZATION AND CHARACTER 3343
TIME COURSE 3344
CONTEXTUAL INFORMATION 3345
PHYSICAL EXAMINATION 3348
DIAGNOSTIC TESTING IN ABDOMINAL PAIN 3349
Mechanisms of Visceral Pain 3349
VISCERAL NOCICEPTION 3350
CENTRAL PROCESSING OF SOMATIC AND
5989
HYPERSENSITIVITY
Susceptibility Factors 3355
GENETIC FACTORS 3355
ADVERSE LIFE EVENTS AND STRESS 3356
PSYCHIATRIC DISEASES 3357
MICROBIAL COLONIZATION 3358
Biomarkers of Abdominal Pain 3358
Treatment of Abdominal Pain 3360
LIFESTYLE MODIFICATIONS 3360
PATIENT–PROVIDER RELATIONSHIP 3362
PLACEBO RESPONSE 3362
OPIOIDS 3363
NONOPIOID ANALGESICS 3364
NEUROMODULATORS 3365
ANTIDEPRESSANTS 3365
PSYCHOLOGICAL THERAPIES 3366
BLOCKING AFFERENT PATHWAYS 3367
SMOOTH MUSCLE RELAXANTS 3369
ACID SUPPRESSANTS 3370
ALTERING THE MICROBIOME 3370
SEROTONIN 3371
SUBSTANCE P 3372
COMPLEMENTARY AND ALTERNATIVE
3372
MEDICINE THERAPY
Conclusion 3374
CHAPTER 64: Pelvic Pain in Females 3392
Acute Pelvic Pain 3393

INTRODUCTION 3393

5990
CHAPTER 64: Pelvic Pain in Females 3392
Acute Pelvic Pain 3393
INTRODUCTION 3393
OVERVIEW OF ASSESSMENT 3394

GYNECOLOGIC FACTORS 3395

Pelvic Inflammatory Disease 3395
Adnexal Pathology 3397
Hematometra/Hematocolpos 3398
Acute Exacerbation of Chronic Pelvic Pain 3398
COMPLICATIONS SPECIFIC TO PREGNANCY 3399
Ectopic Pregnancy 3400
Miscarriage 3401
Fibroid Degeneration 3402
Ovarian Cyst Accident 3403
Ligamentous Stretch 3403
Urinary Retention and Uterine Incarceration 3403
COMPLICATIONS OF ASSISTED CONCEPTION 3404
Ovarian Hyperstimulation Syndrome 3404
Pelvic Infection 3406
Dysmenorrhea 3406
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS 3407
HORMONAL TREATMENTS 3408
SURGICAL TREATMENTS 3408
NONPHARMACOLOGIC INTERVENTIONS 3409
Mittelschmerz 3409
Chronic Pelvic Pain 3410
INTRODUCTION 3410
FACTORS ASSOCIATED WITH CHRONIC PELVIC
3410

5991
Abuse 3410
Psychological 3411
Personality 3411
OVERVIEW OF ASSESSMENT 3412
History 3412
Examination 3413
Investigations 3413
Therapeutic Trial 3414
Diagnostic Laparoscopy 3415
Empirical Treatment 3415
THE IMPORTANCE OF VISCERAL
3416
HYPERSENSITIVITY IN CHRONIC PELVIC PAIN
GYNECOLOGIC FACTORS IN CHRONIC PELVIC
3416
PAIN
Endometriosis 3416
Adenomyosis 3420
Adhesions 3421
Chronic Pelvic Inflammatory Disease 3422
Pelvic Venous Congestion 3422
GASTROINTESTINAL FACTORS IN CHRONIC
3423
PELVIC PAIN
Irritable Bowel Syndrome 3423
Constipation 3423
UROLOGIC FACTORS IN CHRONIC PELVIC PAIN 3424
Interstitial Cystitis/Bladder Pain Syndrome 3424
Urethral Syndrome 3425
MUSCULOSKELETAL FACTORS IN CHRONIC
PELVIC PAIN 3425

Fibromyalgia 3426

5992
Trigger Points 3426
Pelvic Floor Abnormalities 3426
Hernia 3427
Sacroiliac Joint Pain 3427
NEUROLOGIC FACTORS IN CHRONIC PELVIC
3428
PAIN
Pudendal Neuropathy 3428
Neuropathy Secondary to a Pfannenstiel Incision 3429
Dyspareunia 3430
OVERVIEW 3430
Vaginismus 3432
Vulval Pain Syndromes 3433
Conclusion 3436
CHAPTER 65: Pelvic Pain in Males 3445
Taxonomy and Phenotyping Chronic Pelvic Pain 3446
CLASSICAL PATHOLOGIES 3447
PELVIC PAIN SYNDROMES AND NONPELVIC
3447
PAIN SYNDROMES
Male Urogenital Pain Syndromes 3449
MALE-SPECIFIC PELVIC PAIN SYNDROMES 3450
SUBCLASSIFICATION OF THE PELVIC PAIN
3450
SYNDROMES BY ORGAN
THE IMPORTANCE OF TAXONOMY AND
3451
PHENOTYPING
Epidemiology 3452
INCIDENCE/PREVALENCE 3452
Prostate Pain Syndrome 3452
Scrotal Pain Syndrome 3453
Penile Pain Syndrome 3453

5993
NONVISCERAL SOMATIC PAINS 3455
PERIPHERAL MECHANISMS 3457
CENTRAL MECHANISMS 3457
MUSCLES AND PELVIC PAIN 3458
Pelvic Muscle Pain Syndromes 3458
Spinal and Abdominal Muscle Pain Syndromes 3460
PELVIC NERVES AND PAIN 3461
Peripheral Nerve Pain Syndromes 3461
Functional Problems and Male Pelvic Pain 3464
Psychological Consequences of Male Pelvic Pain 3465
Male Urogenital Pelvic Pain Syndromes—Treatment 3466
SEX DIFFERENCES AND THERAPIES 3466
SPECIFIC PAIN SYNDROME TREATMENTS 3466
Prostate Pain Syndrome 3466
Scrotal/Testicular/Epididymal Pain Syndromes 3468
GENERIC TREATMENT APPROACH 3469
Psychology and Sexual Counseling 3469
Trigger Point Therapy 3470
Nerve Blocks 3470
Surgery 3470
Drugs 3471
Neuromodulation 3471
Overview and Conclusion 3472
REGIONAL PAIN 3480
CHAPTER 66: Cranial Neuralgias 3480
Classical Trigeminal Neuralgia 3482
HISTORY 3482
EPIDEMIOLOGY 3485

5994
HISTORY 3482
EPIDEMIOLOGY 3485
ETIOLOGY AND PATHOPHYSIOLOGY 3486

SYMPTOMS AND SIGNS 3488

DIFFERENTIAL DIAGNOSIS 3491
TREATMENT 3496
Treatment—Medical Management 3496
Treatment—Nerve and Neurolytic Blockade 3500
Treatment—Surgical 3502
Painful Trigeminal Neuropathy 3507
MULTIPLE SCLEROSIS 3507
NEOPLASM 3508
HERPES ZOSTER AND POSTHERPETIC
3510
NEURALGIA
Etiology 3510
Epidemiology 3510
Symptoms and Signs 3511
Diagnosis 3512
Treatment 3512
Nervus Intermedius Neuralgia 3514
ETIOLOGY 3516
SYMPTOMS AND SIGNS 3516
DIAGNOSIS 3517
TREATMENT 3517
Glossopharyngeal Neuralgia 3517
ETIOLOGY 3519
SYMPTOMS AND SIGNS 3519
DIAGNOSIS 3519

5995
ETIOLOGY 3521
SYMPTOMS AND SIGNS 3521
DIAGNOSIS 3522
TREATMENT 3522
Other Terminal Branch Neuralgias 3522
Other Cranial Neuralgia–Related Causes of Pain:
3524
Anesthesia Dolorosa
ETIOLOGY 3524
SYMPTOMS AND SIGNS 3524
DIAGNOSIS 3524
TREATMENT 3525
Conclusion 3525
CHAPTER 67: Facial Pain 3538
Trigeminal and Other Cranial Nerve Neuropathic
3539
Conditions
TRIGEMINAL NEUROPATHY 3539
Trigeminal Neuralgia Type 1 3540
Trigeminal Neuralgia Type 2 3540
Symptomatic Trigeminal Neuralgia 3541
Neuropathic Trigeminal Neuralgia 3541
Postherpetic Trigeminal Neuralgia 3542
Deafferentation Trigeminal Neuralgia 3542
Atypical Facial Pain 3542
GLOSSOPHARYNGEAL NEURALGIA 3542
NERVUS INTERMEDIUS NEURALGIA 3543
Odontogenic and Temporomandibular Joint Disorders 3544
ODONTOGENIC PAIN 3544

Steps for Diagnosis 3546

5996
Steps for Diagnosis 3546
Dental Findings 3546

Oral Soft Tissue Findings 3549

Radiographic Examination 3549
TEMPOROMANDIBULAR DISORDERS 3550
Chronic Headache Disorders Causing Facial Pain 3554
PRIMARY HEADACHE CONDITIONS 3554
Migraine Headache 3554
Tension Headache 3556
Cluster Headache 3557
Exertional Headache 3558
Hypnic Headache 3559
Secondary Headache Conditions 3559
MEDICATION OVERUSE HEADACHE 3559
SINUS HEADACHES 3560
HEAD INJURY HEADACHES 3561
SHORT-LASTING, UNILATERAL,
NEURALGIFORM HEADACHE ATTACKS WITH 3561
CONJUNCTIVAL INJECTION AND TEARING
SHORT-LASTING, UNILATERAL,
NEURALGIFORM HEADACHE ATTACKS WITH 3562
CRANIAL AUTONOMIC FEATURES
PAROXYSMAL HEMICRANIAS 3562
CONTACT POINT HEADACHE 3563
CHAPTER 68: Neck and Arm Pain 3568
Anatomy of the Neck and Arm 3569
CERVICAL SPINE 3569
Ligaments of the Cervical Spine 3576

5997
VERTEBRAL ARTERIES 3582
CERVICAL NERVES 3583
THE CERVICAL AND BRACHIAL PLEXUS 3586
PECTORAL GIRDLE AND SHOULDER ANATOMY 3601
Epidemiology of Neck and Arm Pain 3609
Evaluation of the Patient 3611
HISTORY AND PHYSICAL EXAMINATION 3611
History 3612
Location/Radiation 3612
Onset 3614
Modifying Factors and Drug History 3615
Associated Symptoms 3615
Family History 3616
Age and Psychosocial History 3616
Past Medical History and Review of Systems 3617
Surgical History 3618
Physical Examination 3619
LABORATORY EVALUATION 3638
RADIOGRAPHIC STUDIES 3639
Common Causes of Neck and Arm Pain 3642
MECHANICAL NECK PAIN AND CERVICOGENIC
3642
HEADACHE
Cervical Spondylosis and Radiculopathy 3642
Cervicogenic Headache 3648
DIFFUSE IDIOPATHIC SKELETAL
3652
HYPEROSTOSIS
CERVICAL RADICULOPATHIES 3653
UPPER EXTREMITY PERIPHERAL NERVE
ENTRAPMENT SYNDROMES AND BRACHIAL 3659

5998
UPPER EXTREMITY PERIPHERAL NERVE
ENTRAPMENT SYNDROMES AND BRACHIAL 3659
PLEXUS NEUROPATHY
Carpal Tunnel Syndrome 3661
Cubital Tunnel Syndrome 3662
LESIONS OF THE BRACHIAL PLEXUS 3664
Acute Brachial Plexus Neuritis 3665
Thoracic Outlet Syndrome 3667
CHAPTER 69: Chest Wall Pain 3679
General Considerations 3679
Anatomy of the Chest Wall 3680
SKELETAL STRUCTURES OF THE CHEST WALL 3680
Thoracic Spine 3681
Ribs 3683
Sternum 3683
JOINTS OF THE CHEST WALL 3684
INTERCOSTAL SPACES 3684
INTERCOSTAL NERVES 3685
Neoplastic Chest Wall Pain 3686
EPIDURAL SPINAL CORD COMPRESSION 3687
SUPERIOR VENA CAVA SYNDROME 3687
COSTOPLEURAL SYNDROME 3688
Nonneoplastic Chest Wall Pain 3689
NEUROPATHIC PAIN 3689
Neuropathic Pain of Central Origin 3690
Peripheral Neuropathic Chest Wall Pain 3691
CHEST WALL PAIN OF SKELETAL ORIGIN 3695
Abnormalities of the Thoracic Spine 3695
Costochondral Dislocation 3703

5999
Chest Wall Pain of Myofascial Origin 3704
Breast Pain 3705
Postsurgical Chest Wall Pain 3706
CHEST PAIN AND PSYCHOLOGICAL FACTORS 3709
CHEST WALL PAIN OF CARDIAC ORIGIN 3710
Conclusion 3710
CHAPTER 70: Lower Extremity Pain 3750
Lumbosacral Plexopathy 3750
NEOPLASMS 3753
RADIATION-INDUCED PLEXOPATHY 3755
DIABETIC AND NONDIABETIC LUMBOSACRAL
3756
RADICULOPLEXUS
ABSCESS 3756
RETROPERITONEAL HEMATOMA 3757
ANEURYSMS 3757
TRAUMA 3758
OBSTETRIC-RELATED PLEXOPATHY 3758
Specific Nerve Entrapment Syndromes 3759
LATERAL FEMORAL CUTANEOUS NERVE
3759
ENTRAPMENT
Etiology 3761
Symptoms and Signs 3761
Diagnosis 3762
Treatment 3763
FEMORAL NERVE ENTRAPMENT 3764
Etiology 3766
Symptoms and Signs 3767
Diagnosis 3767
Treatment 3768

6000
FEMORAL NERVE ENTRAPMENT 3764
Etiology 3766
Symptoms and Signs 3767
Diagnosis 3767
Treatment 3768
SAPHENOUS NERVE ENTRAPMENT 3769
Etiology 3770
Symptoms and Signs 3771
Diagnosis 3771
Treatment 3772
OBTURATOR NERVE ENTRAPMENT 3772
Etiology 3773
Symptoms and Signs 3774
Diagnosis 3775
Treatment 3775
SCIATIC NERVE ENTRAPMENT 3776
Etiology 3778
Symptoms and Signs 3779
Diagnosis 3781
Treatment 3781
FIBULAR (PERONEAL) NERVE ENTRAPMENT 3782
Etiology 3784
Symptoms and Signs 3785
Diagnosis 3786
Treatment 3786
Foot Pain 3787
PES PLANUS 3787
Etiology 3787
Symptoms and Signs 3788

6001
Diagnosis and Treatment 3789
PLANTAR FASCIITIS 3790
Etiology 3790
Symptoms and Signs 3790
Diagnosis and Treatment 3790
HEEL PAD DEFICIENCY 3791
Etiology 3791
Symptoms and Signs 3791
Diagnosis and Treatment 3792
TARSAL TUNNEL SYNDROME 3792
Anatomy 3792
Etiology 3792
Symptoms and Signs 3793
Diagnosis 3793
Treatment 3794
LISFRANC JOINT INSTABILITY 3794
Etiology 3794
Symptoms and Signs 3795
Diagnosis 3795
Treatment 3795
POSTERIOR TIBIAL TENDON INSUFFICIENCY 3795
Etiology 3795
Symptoms and Signs 3796
Diagnosis 3796
Treatment 3796
DORSAL FOOT GANGLIA 3796
Etiology 3796
Symptoms and Signs 3796
Diagnosis and Treatment 3797
6002
Symptoms and Signs 3796
Diagnosis and Treatment 3797
METATARSALGIA 3797
Etiology 3797
Symptoms and Signs 3797
Diagnosis 3798
Treatment 3798
HALLUX VALGUS 3798
Etiology 3798
Symptoms and Signs 3799
Diagnosis 3799
Treatment 3800
HALLUX RIGIDUS 3800
Etiology 3800
Symptoms and Signs 3801
Diagnosis 3801
Treatment 3801
INTRACTABLE KERATOSIS 3802
Etiology 3802
Symptoms and Signs 3802
Diagnosis 3802
Treatment 3802
SESAMOIDITIS 3802
Etiology and Pathophysiology 3802
Symptoms and Signs 3803
Diagnosis 3803
Treatment 3803
GOUT 3803
Etiology 3803

6003
INTERDIGITAL (MORTON’S) NEUROMA 3805
Etiology 3805
Symptoms and Signs 3805
Diagnosis 3806
HAMMERTOES 3808
Etiology 3808
Diagnosis 3808
Treatment 3808
CLAW TOE DEFORMITY 3809
Etiology 3809
Diagnosis 3809
Treatment 3809
HARD CORN (CLAVUS DURUM) 3810
Treatment 3810
SOFT CORN (CLAVUS MOLLUM) 3810
Treatment 3810
INGROWN TOENAIL (ONYCHOCRYPTOSIS) 3811
Treatment 3811
NECK AND LOW BACK PAIN 3820
CHAPTER 71: Neck Pain 3820
Definition 3820
Referred Pain 3821
CERVICOGENIC HEADACHE 3823
Pursuing Diagnosis 3824
TRAUMA 3825
ACUTE NECK PAIN 3826
Serious Conditions 3827
Inflammatory Disorders 3828
Widespread Pain 3829

6004
TRAUMA 3825
ACUTE NECK PAIN 3826
Serious Conditions 3827
Inflammatory Disorders 3828
Widespread Pain 3829
Rare Conditions 3829
Spurious Conditions 3829
Unknown 3830
CHRONIC NECK PAIN 3830
Cervical Disk Stimulation 3831
Medial Branch Blocks 3833
Prevalence 3834
WHIPLASH 3834
Etiology 3835
Clinical Features 3835
Diagnosis 3837
CERVICOGENIC HEADACHE 3838
Differential Diagnosis 3838
Diagnosis 3838
Sources 3839
Minimally Invasive Tests 3839
Prevalence 3841
Treatment 3842
NECK PAIN 3842
Conservative Therapy 3842
Injections 3843
Interventional Pain Medicine 3844
CERVICOGENIC HEADACHE 3846
Summary 3849

6005
CAUSES 3862
Management Algorithm 3864
TRIAGE 3866
Medical History 3868
Psychological and Social History 3875
Physical Examination 3876
Other Examination 3877
Ancillary Investigations 3878
Formulation 3880
INITIAL MANAGEMENT 3881
Pain 3882
REVIEW 3890
VIGILANCE 3891
REINFORCEMENT 3891
Yellow Flags 3891
Discussion 3893
Conclusion 3894
CHAPTER 73: Chronic Low Back Pain 3900
Introduction 3900
DEFINITION 3901
REFERRED PAIN 3901
SOURCES 3903
CAUSES 3903
Lumbar Intervertebral Disks 3903
Lumbar Zygapophysial Joints 3904
PREVALENCE 3904
REFUTED CAUSES 3907
ACCEPTED CAUSES 3907
UNTESTED CAUSES 3908

6006
PREVALENCE 3904
REFUTED CAUSES 3907
ACCEPTED CAUSES 3907
UNTESTED CAUSES 3908
Assessment 3908
MEDICAL HISTORY 3911
PSYCHOSOCIAL HISTORY 3917
PHYSICAL EXAMINATION 3917
REVIEW OF PREVIOUS INVESTIGATIONS 3919
Provisional Diagnosis 3920
Ancillary Investigations 3922
CLEARANCE 3922
NOT INDICATED 3923
MAGNETIC RESONANCE IMAGING 3924
DISK STIMULATION 3926
SINUVERTEBRAL NERVE BLOCKS 3928
LUMBAR MEDIAL BRANCH BLOCKS 3929
SACROILIAC JOINT BLOCKS 3930
SACRAL LATERAL BRANCH BLOCKS 3932
Treatment 3933
GENERAL TREATMENTS 3934
DRUG THERAPY 3934
Paracetamol (Acetaminophen) 3934
Nonsteroidal Anti-inflammatory Drugs 3935
Muscle Relaxants 3935
Benzodiazepines 3935
Antidepressants 3935
Pregabalin 3936
Opioids 3936

6007
Traction 3937
Manual Therapy 3937
McKenzie Therapy 3937
Transcutaneous Electrical Nerve Stimulation 3938
Other Physical and Electrical Modalities 3938
Lumbar Supports 3938
Exercise Therapy 3938
SIMPLE NEEDLE TREATMENTS 3939
Acupuncture 3939
Trigger Point Injection 3940
Prolotherapy 3940
BACK SCHOOL 3940
PSYCHOLOGICAL INTERVENTIONS 3941
MULTIDISCIPLINARY PAIN MANAGEMENT 3941
FUNCTIONAL RESTORATION 3944
SPECIFIC, TARGETED TREATMENTS 3945
Discogenic Pain 3945
Zygapophysial Joint Pain 3948
Sacroiliac Pain 3952
INVASIVE TREATMENTS 3956
Implanted Devices 3956
Spinal Surgery 3956
Conclusion 3957
CHAPTER 74: Surgery for Low Back Pain 3971
Rationale 3972
Effectiveness 3973
BEFORE EVIDENCE-BASED MEDICINE 3973
ADVENT OF EVIDENCE-BASED MEDICINE 3975
SINCE EVIDENCE-BASED MEDICINE 3978

6008
Rationale 3972
Effectiveness 3973
BEFORE EVIDENCE-BASED MEDICINE 3973
ADVENT OF EVIDENCE-BASED MEDICINE 3975
SINCE EVIDENCE-BASED MEDICINE 3978
Discussion 3980
CHAPTER 75: Failed Back Surgery 3984
Causes of Failed Back Surgery 3985
MISMATCH: SURGERY NEEDED VERSUS
3985
SURGERY PERFORMED (“WRONG SURGERY”)
INCOMPLETE EVALUATION AND/OR
3987
DIAGNOSIS (“RESIDUAL PATHOLOGY”)
COMPLICATIONS 3988
TECHNICAL FAILURE 3989
RESIDUAL PATHOLOGY 3989
Spinal Pathology 3989
Extraspinal Pathology 3989
RECURRENT PATHOLOGY 3991
NEW PATHOLOGY 3991
Structural Etiologies of Failed Back Surgery 3991
FORAMINAL STENOSIS 3993
PAINFUL DISK (DISCOGENIC PAIN) 3994
DISK HERNIATION 3995
FACET JOINT PAIN 3995
SACROILIAC JOINT PAIN 3996
SPINAL STENOSIS AND AXIAL LOW BACK PAIN 3996
NEUROPATHIC PAIN 3997
EPIDURAL FIBROSIS 3998
DECONDITIONING 3998

6009
Preoperative Versus Current Pain 4002
Location of Pain (Especially Low Back Pain Versus Leg
4002
Pain)
Response to Mechanical Changes 4002
Quality of Pain 4003
TIME COURSE OF APPEARANCE OF PAIN 4003
Preoperative Low Back Pain or Leg Pain Never
4003
Improves or Early Onset of Old Symptoms
New Leg Pain Soon after Surgery 4003
Pain Improves but Recurs 1 to 6 Months after Surgery 4003
Pain Improves but Recurs and Is Different 4004
ROLE OF RADIOLOGIC EVALUATION OF
4004
FAILED BACK SURGERY
ROLE OF DIAGNOSTIC INJECTIONS 4005
Anesthetic Injections 4005
Provocation Disk Injections (Discography) 4005
Treatments 4005
NONSPECIFIC TREATMENTS 4006
Rehabilitation and Exercise 4006
Medications 4007
SOME OF THE SPECIFIC TREATMENTS FOR
4008
SPECIFIC DISORDERS
Discogenic Pain 4008
Facet Joint Pain 4008
Sacroiliac Joint Pain 4008
Spinal Stenosis 4009
Neuropathic Pain 4009
Lysis of Adhesions 4009
Psychological Interventions 4010

6010
Spinal Stenosis 4009
Neuropathic Pain 4009
Lysis of Adhesions 4009
Psychological Interventions 4010
Reoperation 4010
CHAPTER 76: Psychological Screening of Candidates
4017
for Spine Surgery or Placement of Implanted Devices
Introduction 4017
SPINAL SURGERY 4019
SPINAL CORD STIMULATION AND
4021
INTRATHECAL DRUG DELIVERY SYSTEMS
AFFECTIVE DISORDERS AS PREDICTORS OF
4023
OUTCOME
SOMATIZATION 4026
PAIN SENSITIVITY 4027
ANGER 4028
Cognitive Factors 4029
COPING STRATEGIES 4030
Behavioral Factors 4031
EARLY-LIFE TRAUMA AND ABUSE 4032
SUBSTANCE ABUSE 4032
COMPONENTS OF PSYCHOLOGICAL
4033
EVALUATIONS
VALIDATED PSYCHOLOGICAL MEASURES 4036
Pain Intensity Measures 4036
Mood and Personality 4038
Functional Capacity and Activity Interference Measures 4039
Pain Beliefs 4040
ELECTRONIC PAIN ASSESSMENT PROGRAMS 4042

6011
CHAPTER 77: Rational Pharmacotherapy for Pain 4056
Drugs Are Both Underused and Overused in Pain
4057
Management
Pharmacotherapy Alone Is Rarely Optimal Therapy for
4058
Chronic Pain
EVERY USE OF MEDICATION FOR PAIN IS AN
4059
EXPERIMENT
PATIENT PREFERENCE: SYMPTOM CONTROL
4060
VERSUS SIDE EFFECTS
WHENEVER POSSIBLE TREAT THE CAUSE OF
4061
THE PAIN
SYNERGISM AND POTENTIATION 4061
OUTCOMES ANALYSES OF PAIN
4062
PHARMACOTHERAPY
APPROVED DRUGS AND DRUGS FOR
4064
NONAPPROVED USES
RATIONAL PHARMACOTHERAPY 4066
Conclusion 4067
CHAPTER 78: Nonsteroidal Anti-inflammatory Drugs
4069
and Acetaminophen
Mechanism of Action 4073
PROSTAGLANDIN SYNTHESIS AND
4073
PHARMACOLOGY
CENTRAL SITES OF ACTION 4073
PERIPHERAL SITES OF ACTION 4074
COX-1 AND COX-2 SELECTIVITY 4074
Induction of COX-2 4076

Pharmacokinetics 4077
ABSORPTION 4077

6012
PERIPHERAL SITES OF ACTION 4074
COX-1 AND COX-2 SELECTIVITY 4074
Induction of COX-2 4076
Pharmacokinetics 4077
ABSORPTION 4077
Oral 4077

Injectables 4078
Topical 4078
Intranasal 4081
DISTRIBUTION 4081
ELIMINATION 4082
PATHOPHYSIOLOGIC CONDITIONS AFFECTING
4082
THE KINETICS OF NSAIDS
Renal Failure 4082
Hepatic Disease 4083
Specific Drugs 4083
SALICYLATES 4084
Aspirin 4084
Diflunisal 4084
ACETIC ACID DERIVATIVES 4084
Indomethacin 4084
Sulindac 4085
Tolmetin and Etodolac 4085
Ketorolac 4086
Diclofenac 4088
PROPIONIC ACID DERIVATIVES 4089
Ibuprofen 4089
Ketoprofen 4090

6013
Naproxen 4090
Oxaprozin 4091
OXICAM DERIVATIVES 4092
Meloxicam 4092
COX-2 SELECTIVE NSAIDs 4093
Celecoxib 4093
Etoricoxib 4094
Valdecoxib and Parecoxib 4094
ACETAMINOPHEN 4095
NSAID Combination Medications 4097
SIDE EFFECTS, WARNINGS, AND
4099
CONTROVERSIES
Cardiovascular Effects 4099
Allergy and Hypersensitivity 4102
Gastrointestinal Toxicity 4103
Hematologic Effects 4105
Renal Toxicity 4107
Hepatic Toxicity 4108
Central Nervous System Effects 4109
Surgical Complications 4109
Conclusion 4110
DEDICATION 4110
CHAPTER 79: Opioid Analgesics 4120
Classification Based on Interactions with an Opioid
4121
Receptor
Classification Based on Opioid Agonist or Antagonist
4128
Activity
Opioid Pharmacodynamics 4129

6014
The Pharmacodynamic Effects of Opioids 4129
Central Nervous System Opioid Effects 4130
ANALGESIA 4130
MOOD EFFECTS 4131
SEDATION 4132
NAUSEA AND VOMITING 4132
RESPIRATORY DEPRESSION 4133
CONSTRICTION OF THE PUPIL 4135
ANTITUSSIVE EFFECT 4135
HYPOTHALAMIC EFFECTS 4135
CENTRAL NERVOUS SYSTEM EXCITATION 4136
OPIOID TOLERANCE, DEPENDENCE, AND
4136
ADDICTION
THE OPIOID-TOLERANT PATIENT AND OPIOID-
4137
INDUCED HYPERALGESIA
Clinically Observable Tolerance 4137
Proposed Mechanisms of Tolerance 4138
THE OPIOID-DEPENDENT PATIENT 4142
THE OPIOID-ADDICTED PATIENT WITH PAIN 4144
PERIPHERAL EFFECTS OF OPIOIDS 4144
EFFECTS ON SMOOTH MUSCLE AND THE
4145
CARDIOVASCULAR SYSTEM
PRURITUS 4146
OPIOID EFFECTS IN PREGNANCY AND ON THE
4146
NEONATE
ROUTES FOR OPIOID ADMINISTRATION 4147
ALTERNATIVE NONINVASIVE ROUTES 4149
SUBLINGUAL ADMINISTRATION 4149
EPIDURAL, INTRATHECAL, AND
4152

6015
METHADONE 4156
LEVORPHANOL 4158
OXYMORPHONE 4158
OXYCODONE 4158
FENTANYL 4159
MEPERIDINE 4160
CODEINE 4160
HYDROCODONE 4161
PROPOXYPHENE 4161
TRAMADOL 4161
TAPENTADOL 4162
PENTAZOCINE, NALBUPHINE, AND
4162
BUTORPHANOL
BUPRENORPHINE 4163
Abuse-Deterrent Opioid Formulations 4168
Selecting among the Opioids for Clinical Use 4171
Conclusions and Insights into the Future of Opioids for
4171
Pain
BIASED LIGANDS 4172
DEDICATION 4172
CHAPTER 80: Skeletal Muscle Relaxants and
4178
Analgesic Balms
Skeletal Muscle Relaxants 4178
MECHANISM OF ACTION 4182
Types of Skeletal Muscle Relaxants 4184
CENTRALLY ACTING SEDATIVE-HYPNOTIC
MUSCLE RELAXANTS 4184

Chlorzoxazone 4184
Metaxalone 4184

6016
CENTRALLY ACTING SEDATIVE-HYPNOTIC
4184
MUSCLE RELAXANTS
Chlorzoxazone 4184
Metaxalone 4184
Methocarbamol 4184
Carisoprodol 4185
ANTIHISTAMINE MUSCLE RELAXANT 4185
Orphenadrine Citrate 4185
TRICYCLIC ANTIDEPRESSANT-LIKE MUSCLE
4185
RELAXANT
Cyclobenzaprine 4185
γ-AMINOBUTYRIC ACID AGONIST MUSCLE
4187
RELAXANTS
Diazepam 4187
Baclofen 4187
CENTRAL α2 AGONIST MUSCLE RELAXANTS 4187
Tizanidine 4187
Acute Low Back Pain 4188
Chronic Low Back Pain 4189
Topical Analgesic Balms 4190
TOPICAL COUNTERIRRITANTS 4192
Conclusion 4193
CHAPTER 81: Neuropathic Pain Pharmacotherapy 4197
Antidepressants 4199
TRICYCLIC ANTIDEPRESSANTS 4201
SELECTIVE SEROTONIN AND NOREPINEPHRINE
4205
REUPTAKE INHIBITORS
SELECTIVE SEROTONIN REUPTAKE INHIBITORS 4206
Antiepileptics 4206

6017
CARBAMAZEPINE 4214
OXCARBAZEPINE 4215
LAMOTRIGINE 4216
VALPROATE 4216
OTHER ANTICONVULSANTS 4217
Opioids 4217
Tramadol 4220
Tapentadol 4221
NMDA Receptor Antagonists 4221
Systemic Sodium Channel Blockers 4224
Simple Analgesics 4225
Nonsteroidal Anti-inflammatory Agents 4225
Topical Agents 4226
CAPSAICIN 4226
TOPICAL LIDOCAINE PATCHES 4227
TOPICAL KETAMINE 4229
Cannabinoids 4230
Drug Combinations 4234
Future Drugs 4239
Evidence-Based Recommendations for Drug Therapy in
4240
Neuropathic Pain
Intrathecal Drugs for Neuropathic Pain 4241
Neuropathic Pain—Not Only Pharmacotherapy 4242
CHAPTER 82: Local Anesthetics 4260
Physicochemical Properties of Local Anesthetics 4260
MOLECULAR STRUCTURE 4260
CHIRALITY 4261
ACID–BASE BALANCE 4262
LIPOPHILIC–HYDROPHILIC BALANCE 4263

6018
ACID–BASE BALANCE 4262
LIPOPHILIC–HYDROPHILIC BALANCE 4263
Local Anesthetic Pharmacology 4264
PHARMACODYNAMICS 4264
PHARMACOKINETICS 4265
Absorption 4265
Distribution 4267
Biotransformation and Excretion 4267
Effects of Disease States on Local Anesthetic
4267
Pharmacokinetics
Regional Administration of Local Anesthetics for Pain
4268
Relief
DIFFERENTIAL BLOCKADE 4268
SITE OF INJECTION 4269
Neuraxial Anesthesia 4269
Peripheral Nerve Blockade 4271
Intravenous Regional Anesthesia 4271
Infiltration Anesthesia 4272
Topical Anesthesia 4272
POTENCY, ONSET, AND DURATION 4273
pH ADJUSTMENT OF LOCAL ANESTHETICS 4274
VASOCONSTRICTOR EFFECT 4275
MIXTURES OF LOCAL ANESTHETICS 4275
SPECIAL STATES: PREGNANCY 4276
Systemic Administration of Local Anesthetics for Pain
4277
Relief
INTRAVENOUS LIDOCAINE FOR ACUTE
4277
POSTOPERATIVE PAIN
INTRAVENOUS LIDOCAINE FOR CHRONIC
4278

6019
SYSTEMIC TOXICITY 4280
ALLERGIES 4281
METHEMOGLOBINEMIA 4282
Prolonged-Duration Local Anesthetics 4282
PSYCHOLOGICAL TECHNIQUES 4289
CHAPTER 83: Anger and Pain 4289
Cultural Background 4289
Psychoanalytic Background 4290
Current Research in Anger and Its Relation to Pain 4295
PHYSIOLOGIC MECHANISMS IN ANGER AND
4295
PAIN RESEARCH
PSYCHOLOGICAL CONSTRUCTS IN ANGER AND
4299
PAIN RESEARCH
ANGER MANAGEMENT STYLE 4301
Anger-In 4303
Anger-Out 4305
Opioid Deficit Hypothesis and the Role of Endogenous
4307
Opioid Functioning
Measurement of Anger 4309
STATE-TRAIT ANGER EXPRESSION
4311
INVENTORY-2
THE TARGETS AND REASONS FOR ANGER IN
4312
PAIN SUFFERERS
MULTIDIMENSIONAL ANGER INVENTORY 4312
NOVACO ANGER SCALE AND PROVOCATION
4313
INVENTORY
ANGER DISORDERS SCALE 4314
MINNESOTA MULTIPHASIC PERSONALITY
INVENTORY-2-RESTRUCTURED FORM 4314

6020
MULTIDIMENSIONAL ANGER INVENTORY 4312
NOVACO ANGER SCALE AND PROVOCATION
4313
INVENTORY
ANGER DISORDERS SCALE 4314
MINNESOTA MULTIPHASIC PERSONALITY
4314
INVENTORY-2-RESTRUCTURED FORM
Psychotherapeutic Management 4314
CONSIDERATIONS IN THE SELECTION OF
4317
PSYCHOTHERAPY
BEHAVIORAL AND COGNITIVE-BEHAVIORAL
4319
THERAPIES
Summary 4322
CHAPTER 84: Cognitive-Behavioral Therapy for
4331
Chronic Pain
Introduction 4331
HISTORY AND DEVELOPMENT OF COGNITIVE-
4332
BEHAVIORAL THERAPY FOR PAIN
EVIDENCE FOR COGNITIVE-BEHAVIORAL
4333
THERAPY FOR CHRONIC PAIN
Components of Cognitive-Behavioral Therapy for
4334
Chronic Pain
CHRONIC PAIN PSYCHOEDUCATION 4335
Education about the Neurobiology of Chronic Pain 4336
Resetting Expectations about the Outcomes of Chronic
4336
Pain—the A-B-C Model
Changing Behaviors—SMART Method 4338
RELAXATION TECHNIQUES 4338
BEHAVIORAL ACTIVATION AND TIME-BASED
4341
PACING
SLEEP HYGIENE 4343

6021
THIRD-WAVE THERAPIES—ACCEPTANCE AND
4349
COMMITMENT THERAPY
TREATING COMORBID CONDITIONS 4350
Depression and Anxiety 4350
Posttraumatic Stress Disorder 4351
COGNITIVE-BEHAVIORAL THERAPY WITHIN
INTERPROFESSIONAL PAIN PROGRAMS AND 4352
PAIN REHABILITATION PROGRAMS
Effectiveness of Interprofessional Pain Management
4352
Programs and Pain Rehabilitation Programs
COGNITIVE-BEHAVIORAL THERAPY TO
PREVENT THE TRANSITION FROM ACUTE TO 4353
CHRONIC PAIN
Summary 4354
CHAPTER 85: Pain and Anxiety and Depression 4360
Prevalence of Anxiety and Depressive Disorders in
4360
Chronic Pain
Impact of Anxiety and Depressive Disorders on
4362
Functioning
The Interaction of Anxiety, Depression, and Chronic
4365
Pain
THE FEAR-AVOIDANCE MODEL 4366
A Contextual Behavioral Approach to Anxiety and
4367
Depressive Disorders
Treatment of Anxiety and Depressive Disorders 4369
EVIDENCE FROM PHARMACOLOGIC
APPROACHES 4369

EVIDENCE FROM PSYCHOLOGICAL

4371
APPROACHES
COGNITIVE-BEHAVIORAL THERAPY FOR
6022
Treatment of Anxiety and Depressive Disorders 4369
EVIDENCE FROM PHARMACOLOGIC
4369
APPROACHES
EVIDENCE FROM PSYCHOLOGICAL
4371
APPROACHES
COGNITIVE-BEHAVIORAL THERAPY FOR
CHRONIC PAIN: EFFECTS ON DEPRESSION AND 4372
ANXIETY
Developments in Cognitive Behavioral Therapy 4373
Summary 4376
CHAPTER 86: Hypnosis 4383
History of Hypnosis in Pain and Symptom Control 4383
Hypnosis by Definition 4386
CONSCIOUS, UNCONSCIOUS, AND CONTENT OF
4387
CONSCIOUSNESS
Central Mechanisms 4389
CENTRAL MECHANISMS OF HYPNOSIS 4389
HIGH AND LOW HYPNOTIZABILITY 4390
CENTRAL MECHANISMS OF HYPNOTIC
4391
ANALGESIA
Pain as a Plastic Experience 4394
Testing Hypnotizability 4396
Current Research and Applications of Medical Hypnosis
4398
for Pain
EFFICACY AND EFFECTIVENESS 4400
REVIEW OF RESEARCH STUDIES ACCORDING
4403
TO PAIN PROBLEMS OR SITUATIONS
Perioperative and Procedural Uses 4404
Complex Regional Pain Syndrome 4406
Phantom Limb Pain 4407
6023
Irritable Bowel Syndrome 4414
Headaches 4415
Cancer 4416
Osteoarthritis 4418
Medical Hypnosis Techniques 4418
PRINCIPLES OF PREPARATION, INDUCTION,
4418
AND SUGGESTIONS
COMMON INDUCTION PROCEDURES 4421
SUGGESTIONS AND IMAGERY 4423
Chronic Pain Management 4426
ERICKSONIAN NATURALISTIC APPROACHES TO
4429
PAIN AND SYMPTOM MANAGEMENT
Conclusions 4431
CHAPTER 87: Group Therapy for Chronic Pain 4441
Rationale and Basic Considerations of Group Treatment
4442
for Pain
EVIDENCE FOR EFFICACY OF GROUP
TREATMENT FOR CHRONIC PAIN 4442
MANAGEMENT
GROUP VERSUS INDIVIDUAL TREATMENT 4442
GROUP COGNITIVE-BEHAVIORAL THERAPY
VERSUS WAIT-LIST, TREATMENT AS USUAL, 4447
OR OTHER GROUP TREATMENTS
BEHAVIORAL VERSUS EXERCISE AND
4467
PHYSICAL THERAPY GROUP TREATMENTS
MINDFULNESS-BASED APPROACHES TO PAIN
MANAGEMENT 4468

ACCEPTANCE-BASED APPROACHES TO PAIN

4473
MANAGEMENT

6024
MINDFULNESS-BASED APPROACHES TO PAIN 4468
MANAGEMENT
ACCEPTANCE-BASED APPROACHES TO PAIN
4473
MANAGEMENT
Factors Affecting Psychotherapeutic Outcome 4476

THE IMPORTANCE OF COGNITIVE CHANGE 4477

COMPLIANCE WITH HOMEWORK AND SKILLS
4479
PRACTICE TO MAINTAIN TREATMENT GAINS
IMPORTANCE OF THERAPIST SKILL AND
4480
ADEQUATE TIME WITH THERAPIST
IMPORTANCE OF GROUP PROCESS 4481
Advantages of Group Treatment 4482
EFFICIENCY AND COST-EFFECTIVENESS 4482
SOCIAL PROXIMITY AND SUPPORT 4483
VICARIOUS LEARNING AND MODELING OF
4483
COLLABORATIVE APPROACH
INTERPERSONAL GROUP PROCESS 4484
Practical Issues 4485
OPEN VERSUS CLOSED GROUPS 4485
LENGTH OF GROUP 4485
NUMBER OF PARTICIPANTS 4486
INDIVIDUALS WHO MAY BE INAPPROPRIATE
4487
FOR GROUPS
Summary and Conclusions 4487
Future Directions 4488
Appendix 87.1: Search Strategies 4490
CHAPTER 88: Motivating Chronic Pain Patients for
4500
Behavioral Change
Neural Mechanisms of Motivation 4502

6025
MOTIVATION ENHANCEMENT THERAPY 4507
Help Patients Recognize the Problems and Goals 4508
DECISIONAL BALANCE 4510
SELF-MOTIVATIONAL STATEMENTS 4511
What Not to Do in Motivation Enhancement Therapy 4513
Dealing with Setbacks and Resistance 4514
SIMPLE REFLECTION 4515
AMPLIFIED REFLECTION 4516
DOUBLE-SIDED REFLECTION 4516
AGREEMENT WITH TWIST 4517
PERSONAL CHOICE AND CONTROL 4517
SHIFTING FOCUS 4518
Research Outcomes 4518
Volitional Approach: Implementation Intentions 4520
IMPLEMENTATION INTENTIONS: OUTCOMES 4522
Conclusion 4523
PHYSICAL AND OTHER NONINTERVENTIONAL
4529
THERAPEUTIC MODALITIES
CHAPTER 89: Basic Concepts in Biomechanics and
4529
Musculoskeletal Rehabilitation
Basic Considerations 4530
KINETIC CHAIN THEORY 4530
ADVERSE NEURAL TENSION 4532
Lower Limb 4534
Upper Limb 4535
NEUROMUSCULAR CONTROL 4537
BIOMECHANICAL CONSIDERATIONS IN THE
SETTING OF COMMON PHYSICAL 4538
EXAMINATION TECHNIQUES

6026
Biomechanical Considerations in Common
4542
Musculoskeletal Pain Syndromes
CERVICALGIA 4543
PERISCAPULAR AND THORACIC PAIN 4545
LUMBAR PAIN 4549
SACROILIAC AND HIP GIRDLE PAIN 4551
Conclusion 4555
CHAPTER 90: Pain Rehabilitation 4560
Historical Overview: Pain Rehabilitation and Functional
4560
Restoration
HISTORY OF PAIN REHABILITATION 4560
HISTORY OF FUNCTIONAL RESTORATION AND
4562
WORK REHABILITATION
WHAT IS PAIN REHABILITATION? 4563
STAKEHOLDERS IN REHABILITATION 4564
Models of Rehabilitation 4566
BIOPSYCHOSOCIAL APPROACH VERSUS
4566
BIOMEDICAL MODEL FOR PAIN MANAGEMENT
TREATMENT APPROACHES: PAIN
4569
REHABILITATION
Acute Rehabilitation 4569
More Comprehensive Team Models: A Pain Continuum 4570
Multidisciplinary Treatment 4571
Interdisciplinary Treatment 4572
Outcomes of Multi- and Interdisciplinary Treatment
4573
Programs
Team Building and Stakeholder Coordination 4574
CASE MANAGEMENT 4574
APPLYING TEAM VALUES 4576

6027
Rehabilitation Specialists: Activities and Conceptual 4578
Models
THE THERAPIST’S ROLE: BUILDING AN
4579
EFFECTIVE THERAPEUTIC RELATIONSHIP
INCORPORATING BEHAVIORAL APPROACHES
4580
IN PAIN REHABILITATION
PHYSICAL THERAPY 4581
THERAPEUTIC EXERCISE 4582
EXERCISE PRESCRIPTION 4584
OCCUPATIONAL THERAPY 4585
Activities of Daily Living 4585
Pacing 4587
PAIN PSYCHOLOGY 4588
RELAXATION TRAINING 4589
Work Rehabilitation: Work Conditioning and Work
4591
Hardening
OUTCOMES OF WORK CONDITIONING AND
4595
WORK HARDENING PROGRAMS
Measuring Physical Capacity 4595
FUNCTIONAL CAPACITY TESTING 4596
FUNCTIONAL CAPACITY TESTING UTILITY 4598
What Does an “Invalid” Test Mean? 4599
Role of Opioid Management in Pain Rehabilitation 4600
Conclusion 4602
CHAPTER 91: Assessment and Treatment of Substance
4612
Use Disorders
Assessment and Treatment of Substance Use Disorders
—Addiction Medicine Perspective 4613

SCREENING AND RECOGNITION 4614

6028
What Does an “Invalid” Test Mean? 4599
Role of Opioid Management in Pain Rehabilitation 4600
Conclusion 4602
CHAPTER 91: Assessment and Treatment of Substance
4612
Use Disorders
Assessment and Treatment of Substance Use Disorders
4613
—Addiction Medicine Perspective
SCREENING AND RECOGNITION 4614
History 4614
Physical Examination 4615
Laboratory 4615
Self-report Questionnaires 4617
PRESCRIPTION DRUG MONITORING PROGRAM 4618
DIAGNOSTIC ASSESSMENT 4618
Co-occurring Psychiatric Disorders 4620
MONITORING DURING ONGOING PAIN
4621
TREATMENT
TREATMENT AND/OR REFERRAL 4621
Brief Interventions 4622
Specialty Substance Use Disorders Treatment 4623
Medically Supervised Withdrawal 4623
Opioid Maintenance Treatment 4624
Intensive Outpatient Treatment 4625
Inpatient Treatment 4626
Specific Behavioral Treatments 4626
Pharmacotherapies 4629
Conceptions of Opioid Use Disorder—The Pain
4640
Medicine Perspective
HISTORY OF OPIOID USE FOR CHRONIC PAIN

6029
Conclusions: Bridging the Gap between Addiction and 4649
Pain Medicine
CHAPTER 92: Biophysical Agents for Pain
4656
Management in Physical Therapy
Superficial Thermal Agents 4658
THERMOTHERAPY 4658
CRYOTHERAPY 4661
Light Therapy 4663
LASER 4663
MONOCHROMATIC INFRARED ENERGY 4666
Therapeutic Ultrasound 4667
Electrical Current 4672
TRANSCUTANEOUS ELECTRICAL NERVE
4672
STIMULATION
INTERFERENTIAL CURRENT 4675
IONTOPHORESIS 4677
Somatosensory Desensitization 4680
Emerging Interventions 4683
MANUAL LYMPHATIC DRAINAGE 4683
CUPPING 4684
MIRROR THERAPY AND GRADED MOTOR
4689
IMAGERY
Conclusion 4691
CHAPTER 93: Exercise Therapy for Low Back Pain 4705
Individualized Exercise Programs 4708
MUSCULOSKELETAL EXAMINATION FOR LOW
4708
BACK PAIN
DESIGNING INDIVIDUALIZED EXERCISE
4710
PROGRAMS

6030
MUSCULOSKELETAL EXAMINATION FOR LOW 4708
BACK PAIN
DESIGNING INDIVIDUALIZED EXERCISE
4710
PROGRAMS
EXERCISE RECOMMENDATIONS BASED ON THE
CLINICAL COURSE 4711

Acute Lower Back Pain 4711

Subacute Lower Back Pain 4712
RECURRENT LOWER BACK PAIN STAGE OF
4712
MANAGEMENT
PERSISTENT LOWER BACK PAIN STAGE OF
4712
MANAGEMENT
Quota Programs for Exercise Dosage 4713
RELAPSE MANAGEMENT 4714
THE APPLICATION OF COMMON EXERCISE
4714
APPROACHES FOR LOWER BACK PAIN
Specific Exercise 4714
Global Exercise 4717
Psychological and Educational Approaches 4719
Evidence to Support Exercise Therapy for Lower Back
4720
Pain
EVIDENCE FOR SPECIFIC EXERCISE
4720
APPROACHES
Efficacy of Spinal Stabilization Exercises 4720
Efficacy of Directional Preference Exercises 4722
EVIDENCE FOR USING CLASSIFICATION
4722
SYSTEMS FOR EXERCISE SELECTION
Matching the Exercise Program to the Patient 4722
EVIDENCE FOR GLOBAL EXERCISE
4724

6031
MEDICINE
COMPLEMENTARY AND INTEGRATIVE HEALTH 4737
BRIDGING THE DIVIDE: ONE KIND OF
4737
MEDICINE
WHAT IS DIFFERENT ABOUT
COMPLEMENTARY AND ALTERNATIVE 4738
MEDICINE?
WHO USES COMPLEMENTARY AND
4740
INTEGRATIVE HEALTH?
CATEGORIZING COMPLEMENTARY AND
4741
INTEGRATIVE HEALTH THERAPIES
Why Consider Complementary and Integrative Health
4743
Therapies in Pain Management?
CHALLENGES OF EVIDENCE-BASED
COMPLEMENTARY AND ALTERNATIVE 4744
MEDICINE THERAPIES
The Complementary and Integrative Health Therapies:
4746
The Evidence
BIOLOGICALLY BASED THERAPIES 4746
Manipulation 4746
Therapeutic Massage 4748
Natural Medicine Therapies 4749
Body Awareness Therapy 4749
Breath Pattern Retraining 4750
Prolotherapy 4751
The Tensegrity Model 4752
The Fascia Model 4752
Trigger Point Manipulation 4753
ENERGY-BASED THERAPIES 4754
Veritable Energy Therapies 4755
6032
Prolotherapy 4751
The Tensegrity Model 4752
The Fascia Model 4752
Trigger Point Manipulation 4753
ENERGY-BASED THERAPIES 4754
Veritable Energy Therapies 4755
Putative Energy Therapies 4757
Biofield Therapies 4761
Conclusion 4764
IMPLANTED ELECTRICAL STIMULATORS 4771
CHAPTER 95: Stimulation of the Peripheral Nervous
4771
System for Pain Relief
Pathophysiology and Mechanisms of Analgesia 4773
Stimulation Technologies 4774
Implantation Techniques 4777
OPEN SURGICAL PLACEMENT 4778
PERCUTANEOUS PLACEMENT WITH
4780
FLUOROSCOPIC GUIDANCE
PERCUTANEOUS PLACEMENT WITH
4781
ULTRASOUND GUIDANCE
PLACEMENT AT THE NERVE ROOT/DORSAL
4782
ROOT GANGLION
Patient Selection and Preoperative Workup 4783
Clinical Indications and Outcomes 4784
EXTREMITY PAIN 4785
Peripheral Nerve Stimulation 4785
Brachial and Lumbar Plexus Stimulation 4786
Dorsal Root Ganglion Stimulation 4786
TRUNCAL PAIN 4787

6033
HEADACHE AND FACIAL PAIN 4789
Occipital Neuralgia 4791
Migraine Headache 4791
Cluster Headache 4793
Trigeminal Neuralgia and Facial Pain 4793
Complications 4794
PERIPHERAL NERVE STIMULATION 4794
PERIPHERAL FIELD STIMULATION 4795
DORSAL ROOT GANGLION STIMULATION 4795
Conclusion and Future Directions 4796
CHAPTER 96: Spinal Cord Stimulation 4803
History 4803
Basic Science of Conventional Spinal Cord Stimulation 4805
INTRODUCTION 4806
NEUROPHYSIOLOGY AND NEUROCHEMISTRY 4806
Basic Science of New Spinal Cord Stimulation
4811
Waveforms
HIGH-FREQUENCY SPINAL CORD
4811
STIMULATION
BURST SPINAL CORD STIMULATION 4813
MODERATE CHANGES OF CONVENTIONAL
4815
SPINAL CORD STIMULATION PARAMETERS
COMPUTER MODELING STUDIES 4816
CONVENTIONAL SPINAL CORD STIMULATION
4818
MECHANISMS IN ISCHEMIC PAIN
PERIPHERAL VASCULAR DISEASE 4818
SPINAL CORD STIMULATION FOR ANGINA
PECTORIS AND CARDIAC DISEASE 4820

MECHANISMS OF SPINAL CORD STIMULATION

6034
PERIPHERAL VASCULAR DISEASE 4818
SPINAL CORD STIMULATION FOR ANGINA
4820
PECTORIS AND CARDIAC DISEASE
MECHANISMS OF SPINAL CORD STIMULATION 4824
IN VISCERAL ABDOMINAL PAIN
Indications 4826
NEUROPATHIC PAIN 4826
ISCHEMIC PAIN 4827
VISCERAL PAIN AND DYSFUNCTION 4828
Potential Beneficial Outcomes 4828
TECHNICAL GOAL 4828
CLINICAL GOALS 4828
Prognostic Factors 4829
Patient Selection 4830
Technique 4832
Screening Trial 4832
SCREENING ELECTRODE CHOICE 4832
ELECTRODE POSITIONING 4833
PARAMETER ADJUSTMENT 4833
PROCEDURAL RISK REDUCTION 4833
TRIAL DURATION 4834
REMOVAL OF TRIAL ELECTRODE 4834
Device Options 4834
CHOICE OF ELECTRODE 4835
CHOICE OF PULSE GENERATOR 4837
PROGRAMMING A SPINAL CORD STIMULATION
4837
SYSTEM
Patient Management 4838
SPINAL CORD STIMULATION PATIENT

6035
BIOLOGIC FAILURE 4840
PSYCHOLOGICAL FAILURE 4840
TECHNICAL FAILURE 4840
EQUIPMENT FAILURE 4841
Cost-effectiveness 4841
Spinal Cord Stimulation Challenges 4842
CHAPTER 97: Deep Brain and Motor Cortex
4854
Stimulation
Deep Brain Stimulation 4855
BASIC CONSIDERATIONS 4855
EFFICACY OF DEEP BRAIN STIMULATION 4856
SURGICAL TECHNIQUE 4859
Motor Cortex Stimulation 4861
BASIC CONSIDERATIONS 4861
EFFICACY OF MOTOR CORTEX STIMULATION 4863
SURGICAL TECHNIQUE 4865
Transcranial Magnetic Stimulation 4868
BASIC CONSIDERATIONS 4868
EFFICACY OF REPETITIVE TRANSCRANIAL
4869
MAGNETIC STIMULATION FOR PAIN
Conclusion 4870
INTERVENTIONAL PAIN MANAGEMENT 4876
CHAPTER 98: Diagnostic and Therapeutic Nerve
4876
Blocks
Common Principles 4877
PHYSICIAN 4877

PATIENT 4877
PREPARATION 4878
CONTRAINDICATIONS 4879
6036
PHYSICIAN 4877
PATIENT 4877
PREPARATION 4878
CONTRAINDICATIONS 4879
COMPLICATIONS 4880
Systemic Effects 4880
Physiologic Effects 4882
Damage to Nonneural Structures 4882
Damage to Nerves 4883
PROCEDURE 4883
Blind Techniques 4883
Fluoroscopy-Guided Techniques 4884
Computed Tomography–Guided Techniques 4886
Ultrasound-Guided Techniques 4886
Test Blocks 4888
Prognostic Blocks 4889
SPINAL NERVE BLOCKS 4890
SYMPATHETIC BLOCKS 4892
Diagnostic Blocks 4895
PRINCIPLES 4895
Controls 4895
Criteria for Positive Response 4897
APPLICATIONS 4897
Nerve Blocks for Cervical Zygapophysial Joint Pain 4897
Nerve Blocks for Lumbar Zygapophysial Joint Pain 4900
Other Diagnostic Nerve Blocks 4906
Diagnostic Intra-articular Blocks 4906
Therapeutic Nerve Blocks 4911
Conclusion 4915

6037
CAUDAL INJECTIONS: EVIDENCE 4929
CAUDAL INJECTIONS: ADVERSE EVENTS 4931
INTERLAMINAR INJECTIONS: TECHNIQUE 4931
NONIMAGE-GUIDED INTERLAMINAR
4934
TECHNIQUE: EVIDENCE
IMAGE-GUIDED INTERLAMINAR TECHNIQUE:
4935
EVIDENCE
INTERLAMINAR TECHNIQUE: ADVERSE
4936
EVENTS
TRANSFORAMINAL INJECTIONS 4936
TRANSFORAMINAL INJECTIONS UNDER
4941
FLUOROSCOPIC GUIDANCE: EVIDENCE
TRANSFORAMINAL INJECTIONS:
4946
DETERMINANTS OF EFFICACY
TRANSFORAMINAL INJECTIONS: ADVERSE
4947
EVENTS
TRANSFORAMINAL INJECTIONS UNDER
COMPUTED TOMOGRAPHY GUIDANCE: 4948
EVIDENCE, ADVERSE EVENTS
TRANSFORAMINAL EPIDURAL STEROID
INJECTIONS: THEIR ROLE IN TREATING THE 4949
RADICULAR PAIN PATIENT
CHAPTER 100: Intrathecal Drug Delivery in the
4957
Management of Pain
History of the Development of Intrathecal Drug 4957
Delivery Systems
Basic Pharmacology of Intrathecal Drug Administration 4958
Selection of Agents for Intrathecal Drug Delivery 4960
Specific Agents for Intrathecal Drug Delivery 4963
OPIOIDS 4963

6038
History of the Development of Intrathecal Drug 4957
Delivery Systems
Basic Pharmacology of Intrathecal Drug Administration 4958
Selection of Agents for Intrathecal Drug Delivery 4960
Specific Agents for Intrathecal Drug Delivery 4963
OPIOIDS 4963
Morphine 4963
Hydromorphone 4964
Fentanyl and Sufentanil 4964
Opioid-Induced Hyperalgesia and Intrathecal Opioids 4965
LOCAL ANESTHETICS 4966
α2-ADRENERGIC AGONISTS 4967
CALCIUM CHANNEL ANTAGONISTS 4969
N-METHYL-D-ASPARTATE RECEPTOR
4970
ANTAGONISTS
γ-AMINOBUTYRIC ACID AGONISTS 4971
GABAPENTIN 4971
SOMATOSTATIN AND SOMATOSTATIN
4972
ANALOGUES
TRICYCLIC ANTIDEPRESSANTS 4973
ACETYLCHOLINESTERASE INHIBITORS 4974
ADENOSINE 4974
NITRIC OXIDE 4975
PROSTAGLANDIN INHIBITORS 4975
CALCITONIN GENE-RELATED PEPTIDE
4976
ANTAGONISTS
SUBSTANCE P ANTAGONISTS 4976
Patient Selection for Intrathecal Drug Delivery 4977
Trialing Techniques for Intrathecal Drug Delivery 4980

6039
Complications of Spinal Drug Delivery 4992
SURGICAL COMPLICATIONS 4993
Wound Hematoma/Seroma and Epidural Hematoma 4993
Infectious Complications 4994
Cerebrospinal Fluid Leak and Postdural Puncture
4996
Headache
Neurologic Injury 4997
DEVICE-RELATED COMPLICATIONS 4997
Catheter and Pump Problems 4997
Complications Associated with Refill of the Pump
4999
Reservoir
PHARMACOLOGIC COMPLICATIONS AND
5001
DRUG-RELATED SIDE EFFECTS
Side Effects of Intrathecal Opioids 5001
Opioid Tolerance 5003
Intrathecal Inflammatory Masses (Intrathecal
5005
Granuloma)
Drug Withdrawal 5008
Patient Outcomes and Intrathecal Drug Infusion 5009
CANCER PAIN 5009
INTRATHECAL DRUG DELIVERY FOR CHRONIC
5010
NONCANCER PAIN
Conclusion 5012
ACKNOWLEDGMENT 5013
CHAPTER 101: Intradiscal Therapies for Low Back
5017
Pain
Discogenic Pain 5017
Pathology 5019
Therapies 5026

6040
Conclusion 5012
ACKNOWLEDGMENT 5013
CHAPTER 101: Intradiscal Therapies for Low Back
5017
Pain
Discogenic Pain 5017
Pathology 5019
Therapies 5026
ABLATION 5027
Ramus Communicans Lesions 5027
Intranuclear Radiofrequency 5027
PERCUTANEOUS INTRADISCAL
5028
RADIOFREQUENCY THERMOCOAGULATION
Intradiscal Electrothermal Therapy 5028
L’DISQ 5029
Coblation 5029
Biacuplasty 5029
CHEMICAL THERAPIES 5031
Intradiscal Steroids 5031
Etanercept 5033
Methylene Blue 5034
Antibiotics 5034
Proliferants 5035
BIOLOGICS 5035
Sealant 5036
Platelet-Rich Plasma 5036
α2 Macroglobulin 5036
Stem Cells 5036
Discussion 5037
CHAPTER 102: Neurolytic Blockade for Noncancer
6041
HISTORY AND TRENDS 5047
LIMITATIONS 5047
Chemical Neurolytic Blockade 5049
PRINCIPLES 5049
PHENOL 5049
ALCOHOL 5050
APPLICATIONS 5050
GLYCEROL 5051
Cryoneurotomy 5052
Thermal Radiofrequency 5053
INTRODUCTION 5053
PHYSICS 5053
PATHOLOGY 5056
PHYSIOLOGY 5057
APPLICATIONS 5057
Trigeminal Neuralgia 5057
Central Ablative Procedures 5058
Medial Branch Neurotomy 5061
Sacral Lateral Branch Neurotomy 5078
Discussion 5080
SURGICAL APPROACHES 5091
CHAPTER 103: Surgery of the Peripheral Nervous
5091
System as a Treatment for Pain
Peripheral Neurectomy 5092
BASIC CONSIDERATIONS 5092
Pathophysiology of Neuropathic Pain 5092
Rationale for Neuroma Relocation Surgery 5094
CLINICAL CONSIDERATIONS 5095
Preoperative Evaluation 5095

6042
INDICATIONS AND OUTCOMES FOR
5098
TREATMENT OF NEUROPATHIC PAIN
Amputation Stump Pain 5098
Intercostal and Intercostobrachial Pain 5098
Perineal and Inguinal Pain 5099
Meralgia Paresthetica 5099
Saphenous Neuralgia 5100
Morton’s Neuroma 5100
General Results of Neurectomy for Neuropathic Pain 5100
INDICATIONS AND OUTCOMES FOR
5102
TREATMENT OF NOCICEPTIVE PAIN
Axial Spine Pain 5102
Extremity Joint Pain 5104
Pelvic Pain 5104
Cancer Pain 5104
Nerve Entrapment Release 5105
BASIC CONSIDERATIONS 5105
Pathophysiology of Nerve Entrapment Pain 5105
Nerve Entrapment and Systemic Disease 5106
CLINICAL CONSIDERATIONS 5107
Preoperative Evaluation 5107
Operative Technique 5112
INDICATIONS AND OUTCOMES 5112
Entrapments of the Median Nerve 5112
Entrapments of the Ulnar Nerve 5114
Entrapments of the Radial Nerve 5116
Entrapment of the Suprascapular Nerve 5117
Thoracic Outlet Syndrome 5118
Entrapments of the Lower Extremities 5119

6043
INDICATIONS AND OUTCOMES 5127
Cranial and Cervical Pain 5128
Occipital Neuralgia 5128
Thoracic Pain 5129
Postsurgical Truncal Pain 5129
Sacral Pain 5130
Extremity Pain 5132
Visceral Pain 5133
Axial Spine Pain 5133
Postherpetic Neuralgia 5134
Sympathectomy 5134
BASIC CONSIDERATIONS 5134
Sympathetic Efferents 5134
Sympathetically Maintained Pain 5135
CLINICAL CONSIDERATIONS 5137
Preoperative Evaluation 5137
Operative Techniques 5141
INDICATIONS AND OUTCOMES 5142
POSTOPERATIVE COMPLICATIONS 5143
Conclusion 5144
CHAPTER 104: The Surgical Management of
5159
Trigeminal Neuralgia
Patient Presentation 5159
Anatomy 5160
Pathophysiology 5161
Evaluation for Surgery 5162
Microvascular Decompression 5164
OUTCOMES 5167
Percutaneous Rhizotomy 5168

6044
Pathophysiology 5161
Evaluation for Surgery 5162
Microvascular Decompression 5164
OUTCOMES 5167
Percutaneous Rhizotomy 5168
OUTCOMES 5170
Percutaneous Radiofrequency Rhizotomy 5170
Percutaneous Balloon Compression 5170
Radiosurgery 5171
OUTCOMES 5172
Conclusions 5173
CHAPTER 105: Ablative Neurosurgical Procedures for
5178
Chronic Pain
Dorsal Root Entry Zone Lesioning 5179
INDICATIONS 5179
ANATOMY AND PHYSIOLOGY 5180
TECHNIQUE 5180
OUTCOMES 5181
Cordotomy 5182
INDICATIONS 5182
ANATOMY AND PHYSIOLOGY 5183
TECHNIQUE 5185
OUTCOMES 5186
Cingulotomy 5187
INDICATIONS 5187
ANATOMY AND PHYSIOLOGY 5188
TECHNIQUE 5189
OUTCOMES 5190
Thalamotomy 5191

6045
ANATOMY AND PHYSIOLOGY 5197
TECHNIQUES 5199
OUTCOMES 5200
Conclusion 5201
PART SIX: Provision of Pain Treatment 5207
CHAPTER 106: Interdisciplinary Chronic Pain
Management: Overview and Lessons from the Public 5207
Sector
History of Interdisciplinary Chronic Pain Management 5207
EMPIRICAL SUPPORT FOR INTERDISCIPLINARY
5209
CHRONIC PAIN MANAGEMENT
THEORETICAL BASIS OF THE
5213
INTERDISCIPLINARY APPROACH
COMPOSITION OF THE INTERDISCIPLINARY
5214
TEAM AND ROLES OF MEMBERS
The Process of Interdisciplinary Chronic Pain
5220
Management
Interdisciplinary Chronic Pain Management in Veterans
Healthcare Administration: Overview of a Model 5223
System
Future Considerations for Interdisciplinary Chronic Pain
5227
Management
Conclusion 5228
CHAPTER 107: Spine Clinics 5232
Treatment Components 5235
Treatment Providers 5236
CONSERVATIVE CARE GATEKEEPERS 5236
PAIN MANAGEMENT 5236
PSYCHOLOGY 5237

6046
Future Considerations for Interdisciplinary Chronic Pain 5227
Management
Conclusion 5228
CHAPTER 107: Spine Clinics 5232
Treatment Components 5235
Treatment Providers 5236
CONSERVATIVE CARE GATEKEEPERS 5236
PAIN MANAGEMENT 5236
PSYCHOLOGY 5237
PHYSICAL THERAPY 5237

OCCUPATIONAL THERAPY 5238

SPINE SURGERY 5239
CHRONIC PAIN MANAGEMENT PROGRAM 5240
POTENTIAL BENEFITS OF A SPINE SPECIALTY
5241
CLINIC
COORDINATION OF CARE 5243
RESEARCH AND EDUCATION 5243
Conclusion 5245
CHAPTER 108: Pain Management in Primary Care 5248
Introduction 5248
PREVALENCE OF PAIN IN THE UNITED STATES 5248
ECONOMIC IMPLICATIONS OF CHRONIC PAIN 5248
CHRONIC PAIN MANAGEMENT: THE STATUS
5249
QUO
SEARCHING FOR SOLUTIONS 5250
A New Approach to Chronic Pain Management 5250
WHO TREATS CHRONIC ILLNESS? 5251
WHY PRIMARY CARE IS INVOLVED? 5252

6047
Disagreement among Experts—To Treat and Not to 5254
Treat
Barriers to Treating Pain 5255
Addressing Barriers to Care 5259
MYTHS AND BIASES 5259
PATIENT RESISTANCE 5260
REGULATORY SCRUTINY 5261
PATIENT EXPECTATIONS 5261
Pain Practitioner: A Primary Care Model 5261
TRAINING 5262
COLLABORATION WITH PAIN SPECIALISTS 5262
NEW FOCUS 5262
ASSESSMENT AND EVALUATION DURING
5263
SHORT VISITS
THE 15-MINUTE OFFICE VISIT 5264
Validating the Patient 5264
Assessment Tools 5265
Substance Misuse Screening 5266
Goal Setting and Plan of Action 5266
PHARMACOLOGIC TREATMENT 5267
REFERRAL TO AN ADDICTION SPECIALIST 5269
MOTIVATING BEHAVIOR CHANGE IN PATIENTS
5269
WITH CHRONIC PAIN
Conclusion 5275
CHAPTER 109: Pain Management at the End of Life 5279
Introduction 5279
PALLIATIVE CARE 5280
HOSPICE 5281
Pain Syndromes Common at the End of Life 5282

6048
PALLIATIVE CARE 5280
HOSPICE 5281
Pain Syndromes Common at the End of Life 5282
CANCER 5283
NONCANCER DIAGNOSES 5283
Pain Assessment at the End of Life 5284
CHALLENGES IN PAIN ASSESSMENT 5284
PAIN ASSESSMENT IN THE COGNITIVELY
5285
IMPAIRED
PAIN ASSESSMENT IN THOSE UNABLE TO
5286
COMMUNICATE
PAIN MEASUREMENT IN RESEARCH
5287
CONDUCTED AT END OF LIFE
Pain Management Strategies at End of Life 5287
ROUTES OF DRUG DELIVERY 5287
Oral, Sublingual, Transmucosal, and Buccal Routes 5287
Transmucosal Immediate-Release Fentanyl Products 5288
Enteral and Rectal 5289
Parenteral 5290
Spinal (Epidural/Intrathecal) 5291
Topical 5291
Transdermal 5292
INTRACTABLE PAIN OR UNMANAGEABLE
5292
ADVERSE EFFECTS OF TREATMENT
Effect of Organ Dysfunction on Pharmacokinetics 5293
Myoclonus 5293
Intractable Pain at End of Life 5295
Fears of Hastening Death 5298
Suffering and Existential Distress 5299

6049
Background 5315
MEDICAL ETHICS AND ERIKSON’S GOLDEN
5316
RULE
TRUST 5316
MUTUALITY 5318
MORALS AND ETHICS 5318
Case Vignettes and Analysis 5320
CASE 1: OPIOID-INDUCED HYPERALGESIA 5320
Background and First Attempt at Change of Treatment
5320
Plan to Opioid Cessation
Physician Consultation with a Colleague 5322
Modification in Engagement with Patient and Treatment
5322
Plan following the Consultation and Reflection
Analysis 5323
CASE 2: CHANGE IN THE CENTERS FOR
DISEASE CONTROL AND PREVENTION 5325
GUIDELINES
Background 5325
Analysis 5325
CASE 3: OPIOID PRESCRIPTIONS FROM OTHER
PHYSICIANS FOUND IN CHECK OF STATE DRUG 5327
MONITORING PROGRAM
Background 5327
Analysis 5329
Building Trust through Mutuality 5330
DIALOGUE 5330
EMPATHY 5331
NARRATIVE MEDICINE 5332
Conclusion 5333
CHAPTER 111: Training Pain Specialists 5336
6050
Building Trust through Mutuality 5330
DIALOGUE 5330
EMPATHY 5331
NARRATIVE MEDICINE 5332
Conclusion 5333
CHAPTER 111: Training Pain Specialists 5336
The Evolution of Pain Medicine as a Subspecialty 5336
Pain Medicine as a Primary Medical Specialty 5343
Training in Pain Medicine in Europe 5346
Training and Credentialing in Interventional Pain
5348
Medicine
Conclusion 5351
ACKNOWLEDGMENTS 5353
CHAPTER 112: Emergencies in the Pain Clinic 5356
The American Society of Anesthesiologists Closed
5356
Claims Project
Bleeding Complications 5359
Infectious Complications 5363
Local Anesthetic Systemic Toxicity 5368
UNINTENDED DESTINATIONS FOLLOWING
5370
LOCAL ANESTHETIC ADMINISTRATION
VASOVAGAL REACTIONS 5371
Complications Associated with Intrathecal Drug
5372
Delivery
OPIOID WITHDRAWAL 5374
Anaphylactic and Anaphylactoid Reactions 5375
CATASTROPHIC NEURAL INJURIES AND THE
5377
ADMINISTRATION OF PARTICULATE STEROIDS
Conclusion 5382

6051
The Assessment of Pain in the Emergency Department 5391
Oligoanalgesia in the Emergency Department 5393
Pain and Opioid Abuse in the Emergency Department 5394
Definitions 5395
Pain and “Drug-Seeking Behavior” in the Emergency
5398
Department
Pain and Substance Abuse in the Emergency
5400
Department: A Balanced Perspective
The Example of Sickle Cell Disease 5402
Pain Treatment and Procedural Sedation in the
5403
Emergency Department
Specific Treatment Modalities 5404
NONOPIOIDS 5405
OPIOIDS 5406
PATIENT-CONTROLLED ANALGESIA 5408
ALTERNATIVE DELIVERY ROUTES 5408
PROCEDURAL SEDATION AND ANALGESIA 5408
Evolving Emergency Department Pain Management
5415
Practice
Conclusion 5416
CHAPTER 114: Pain Management in the Intensive Care
5422
Unit
Pain, Analgesia, and Critical Illness 5422
Evaluation and Monitoring of Pain in the Intensive Care
5426
Unit
Managing Pain and Analgesia in the Intensive Care Unit 5430
PHARMACOLOGIC TREATMENT OF PAIN IN THE
5431
INTENSIVE CARE UNIT: PARENTERAL OPIOIDS
Fentanyl 5433

6052
Morphine 5435
Remifentanil 5436
PHARMACOLOGIC TREATMENT OF PAIN IN THE
5437
INTENSIVE CARE UNIT: ADJUVANT THERAPY
Ketamine 5437
Methadone 5438
Other Analgesics and Adjuvant Agents 5439
NONPHARMACOLOGIC MANAGEMENT OF PAIN
5440
IN THE INTENSIVE CARE UNIT
REGIONAL ANESTHETIC APPROACHES TO PAIN
5441
IN THE INTENSIVE CARE UNIT
Integrated Analgesia Management in the Intensive Care
5442
Unit
ANALGOSEDATION IN THE INTENSIVE CARE
5442
UNIT
ANALGESIA AS A COMPONENT OF
COMPREHENSIVE BUNDLED INTENSIVE CARE 5445
UNIT CARE
Pain and Analgesia at the End of Life in the Intensive
5446
Care Unit
Conclusions 5448
ACKNOWLEDGMENTS 5448
CHAPTER 115: The Future of Pain Medicine: An
5457
Epilogue
Index 5464

6053