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Acute Pain: Mechanisms, Management, and Treatment Options

ACUTE PAIN
IT WILL BE POTENTIAL TO KILL YOUR
PATIENTS
Mulyono Soedirman
FK UNHAS / RSPAD GATOT SOEBROTO
JAKARTA
Acute Pain: Mechanisms, Management, and Treatment Options

Overview
Pain: Definition and Features
Physiologic Consequences of Acute Pain
JCAHO and Pain Management
Characteristics of Acute, Chronic, Peripheral
Neuropathic Pain
Assessment of Pain and Pain Relief
Pain Mechanisms
Role of Prostanoids in Pain
Treatment Options for Acute Pain
Other Approaches
Acute Pain Services
Acute Pain: Mechanisms, Management, and Treatment Options

Pain

Definition and Features


Acute Pain: Mechanisms, Management, and Treatment Options

Definition

“Pain is an unpleasant sensory and emotional experience


associated with actual or potential tissue damage or
described in terms of such damage.”

International Association for the Study of Pain. Pain. 1979;6:249.


Acute Pain: Mechanisms, Management, and Treatment Options

Features of Acute Pain


• Onset
• Intensity
• Somatic vs visceral
• May be referred

Siddall PJ, Cousins MJ. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia
and Management of Pain. 3rd ed; 1998:675–713.
Acute Pain: Mechanisms, Management, and Treatment Options

Physiologic Consequences of Acute Pain


Acute Pain: Mechanisms, Management, and Treatment Options

Physiologic Consequences of Acute Pain


• General stress response/neuroendocrine
• Respiratory
• Cardiovascular
• Gastrointestinal/urinary
• Musculoskeletal

Bonica JJ. The Management of Pain. 2nd ed. Vol. 1; 1990.


Acute Pain: Mechanisms, Management, and Treatment Options

General Stress Response

Endocrine/Metabolic
• ↑ ACTH, cortison, catecholamines, interleukin-1
• ↓ insulin

Water/Electrolyte Flux
• H2O, Na+ retention

ACTH = adrenocorticotropic horrmone


Kehlet H. Reg Anesth.1996;21(6S):35–37.
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Respiratory Effects

Acute
Pain

↓ Tidal ↓ Vital ↓ FRC ↓ Alveolar ↓ Mobility


volume capacity ventilation
Atelectasis
Hypostatic pneumonia
V/Q inequality

FRC = functional residual capacity; V/Q = ratio ventilation:perfusion of the lung


Craig DB. Anesth Analg. 1981;60:46.
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Respiratory Effects (Cont’d)


Acute
Pain

Muscle spasm
Muscle splinting
Impaired
ventilation

Cough suppression

Lobular collapse Hypoxemia

Infection/pneumonia
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Cardiovascular Effects

Acute
Pain

Coronary Sympathetic
vasoconstriction overactivity

↑ Anxiety, pain ↑ HR, ↑ PVR, ↑ BP, ↑ cardiac output


• Ischemia
• Angina
• MI Ischemia

MI = myocardial infarction; HR = heart rate; PVR = peripheral vascular resistance; BP = blood


pressure
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Bowler DB, et al. In: Cousins MJ, Phillips GD, eds. Acute Pain Management; 1986:187–236.
Acute Pain: Mechanisms, Management, and Treatment Options

Effects on Peripheral Circulation

Acute
Pain

↓ Limb blood flow1


↓ Venous emptying2
↑ Venous thrombosis/embolism3

1. Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
2. Modig J, et al. Acta Anaesth Scand. 1980;24:305–309.
3. Modig J, et al. Anesth Analg. 1983;62:174–180.
Acute Pain: Mechanisms, Management, and Treatment Options

Gastrointestinal and Urinary Effects

Acute
Gastrointestinal Pain Urinary

↑ Intestinal secretions
Sympathetic
↑ Smooth muscle ↑ Urinary sphincter
overactivity
sphincter tone activity
↓ Intestinal motility
Urinary retention

Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Nimmo WS. Br J Anaesth. 1984.56:29–37.
Acute Pain: Mechanisms, Management, and Treatment Options

Musculoskeletal Effects

Acute
Pain
↑ Muscle
spasm

↑ Sensitivity of peripheral
Sympathetic
nociceptors
overactivity

Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Musculoskeletal Effects (Cont’d)

Acute
Pain

↓ Mobility

Reflex
vasoconstriction

• Impaired muscle
metabolism
• Muscle atrophy
• Delayed normal
muscle function
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Effects on Pain-Signaling Systems

Acute
Pain

↑ Peripheral nociception ↑ Nerve excitability

• Hyperalgesia (1° + 2°)


Prolonged pain • Allodynia

Chronic pain Damaged spinal


pain-signaling systems

Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Psychologic Effects

Acute
Pain

Anxiety

Sleep deprivation

Depression

Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Acute Pain: Mechanisms, Management, and Treatment Options

Other Effects of Acute Pain

• Wound repair
• Impaired immunocompetence
• Hypercoagulable state

Drucker W, et al. J Trauma. 1996;40(3):S116–122.


Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.
Jorgensen L, et al. Br J Anaesth. 1991;66:8–12.
Acute Pain: Mechanisms, Management, and Treatment Options

Advantages of Effective Pain Management

• Patient comfort and satisfaction1,2,3


• Earlier mobilization4
• ↓ hospital stay3,4
• ↓ costs4

1. Eisenach JC, et al. Anesthesiology. 1988;68:444–448.


2. Harrison DM, et al. Anesthesiology. 1988;68:454–457.
3. Miaskowski C, et al. Pain. 1999;80:23–29.
4. Finley RJ, et al. Pain. 1984;2:S397.
Acute Pain: Mechanisms, Management, and Treatment Options

JCAHO and Pain Management


Acute Pain: Mechanisms, Management, and Treatment Options

Joint Commission on Accreditation


of Healthcare Organizations

• New standards in 2000–2001; scoring begins in 2001


• Record pain as the 5th vital sign
• Interdisciplinary management with needs assessment
• Patient’s right to pain assessment
• Monitor pain intervention responses
• Provide pain management education

Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.


Sklar DP. Ann Emerg Med. 1996;27:412–413.
Acute Pain: Mechanisms, Management, and Treatment Options

Pain: The Fifth Vital Sign

• Pain should be considered the “fifth vital sign”


• Patients should be assessed for pain every time pulse,
blood pressure, core temperature, and respiration are
measured
• Healthcare professionals should recognize a report of
unrelieved pain as a “red flag”

American Pain Society Quality Improvement Committee. JAMA. 1995;1847–1880.


Acute Pain: Mechanisms, Management, and Treatment Options

JCAHO Revised Standards: The Patient’s Rights

• Patients have the right to appropriate assessment and


management of pain
• The patient’s right to pain management is respected and
supported
• Patients are involved in all aspects of their care,
including pain management

Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.


Acute Pain: Mechanisms, Management, and Treatment Options

A Team Approach to Implementing the JCAHO


Revised Standards for Pain Management

Others Medical

Nursing
Pharmacy

Managers Dietetic

Rehabilitation
Joint Commission on Accreditation of Healthcare Organizations. Jt Comm Perspect. 1999;19(5):6–8.
Acute Pain: Mechanisms, Management, and Treatment Options

Characteristics of Acute, Chronic,


and Peripheral Neuropathic Pain
Acute Pain: Mechanisms, Management, and Treatment Options

Characteristics of Acute Pain

• Sudden, sharp, intense, localized


• Usually self-limited
• May be associated with physiologic changes, eg,
sweating, ↑ HR, ↑ BP

Siddall PJ, et al. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and
Management of Pain; 1998:675–713.
Acute Pain: Mechanisms, Management, and Treatment Options

Characteristics of Chronic Pain

• Gnawing, aching, diffuse


• No definite beginning or end
• Varies in intensity; may remit briefly
• Associated with psychological and social difficulties
• Acute pain may be superimposed

Siddall PJ, et al. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clinical Anesthesia and
Management of Pain; 1998:675–713.
Acute Pain: Mechanisms, Management, and Treatment Options

Characteristics of Peripheral Neuropathic Pain

• Caused by pathologic changes in peripheral nerves


• Spontaneous pain
• Burning, tingling, numbness
• Allodynia, hyperalgesia

Rathmell JP. Katz JA. In: Benzon H, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:288–294.
Acute Pain: Mechanisms, Management, and Treatment Options

Assessment of Pain and Pain Relief


Acute Pain: Mechanisms, Management, and Treatment Options

Patient’s Perception of Pain

Pain is subjective and may be influenced by:


• Age1,2
• Gender1
• Culture2
• Communication/language skills
• Previous experience

1. Burns JW, et al. Anaesthesia. 1989;44:2–6.


2. Preble L, Sinatra R. In: Sinatra RS, et al, eds. Acute Pain Mechanisms and Management. St. Louis:
Mosby-Year Book; 1992:140–150.
Acute Pain: Mechanisms, Management, and Treatment Options

Benefits of Patient Preparation

• Less postoperative pain1


• Fewer postoperative analgesic medications
• Reduced hospitalization2

1. Croog SH, et al. J Am Dent Assoc. 1994;125:1353–1359.


2. Boeke S, et al. Pain. 1991;45:293–297.
Acute Pain: Mechanisms, Management, and Treatment Options

Example of Measurement Tool for Assessing Pain


Visual Analog Scale (VAS)

No pain Pain as bad as it could possibly be

Carr DB, et al. AHCPR Pub. No. 92–0032. 1992.


Acute Pain: Mechanisms, Management, and Treatment Options

Frequency of Pain Assessment


and Documentation

• Preoperatively
• Routinely at regular intervals postoperatively
• With each new report of pain
• At suitable intervals after each analgesic intervention

Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.


Acute Pain: Mechanisms, Management, and Treatment Options

Pain Mechanisms
Acute Pain: Mechanisms, Management, and Treatment Options

The Somatosensory System


Somatosensory
cortex
Frontal
cortex Thalamus
Hypothalamus
Descending
pathway Ascending tracts
Periaqueductal
gray matter Midbrain

Medulla

Dorsal horn area Spinal cord

Noxious stimuli activate receptors in periphery


Acute Pain: Mechanisms, Management, and Treatment Options

Peripheral Sensitization

Cell Damage Inflammation Sympathetic


Terminals

Release of pain and inflammatory mediators


eg, bradykinin, H+, prostaglandins

High Threshold Nociceptor


• Central
sensitization
Low Threshold • Hyperalgesia
• Allodynia
Spinal cord
Acute Pain: Mechanisms, Management, and Treatment Options

Central Sensitization
Peripheral
Sensitization Tissue Injury

• ↑ C-fiber output
• Hyperalgesia (1°, 2°)
• Allodynia
• Activation of NMDA
receptors

Spinal cord
Acute Pain: Mechanisms, Management, and Treatment Options

Hyperalgesia
Primary
• Sensitization of primary neurons → ↓ threshold to noxious stimuli within site
of injury
• May include response to innocuous stimuli
• ↑ pain from suprathreshold stimuli
• Spontaneous pain
Secondary
• Sensitization of primary neurons in surrounding uninjured areas
• May involve:
– Peripheral sensitization
– Central sensitization

Raja SN, et al. In: Wall PB, Melzack R, eds. Textbook of Pain. 4th ed; 1999:11–57.
Acute Pain: Mechanisms, Management, and Treatment Options

Allodynia
• Pain evoked by innocuous stimuli
• Central sensitization → pain produced by Aβ fibers1
• Possibly mediated by spinal NMDA receptors2

1. Woolf CJ. Drugs. 1994;47(suppl 5):1–9.


2. Dolan S, Nolan AM. Neuroreport. 1999;10(3):449–452.
Acute Pain: Mechanisms, Management, and Treatment Options

Pain Mediators
Cell Damage

Brain
Aa K+ BK

PG

Nociceptor

Spinal cord

HISTAMINE

Mast Cell
Peptides, eg, SUBSTANCE P
SEROTONIN

Platelet
Aa = arachidonic acid; BK = bradykinin; PG = prostaglandin
Acute Pain: Mechanisms, Management, and Treatment Options

Role of Neurotransmitters
Excitatory
• Glutamate, aspartate, ATP
• Mediate afferent synaptic transmission

Inhibitory
• GABA, glycine, norepinephrine, 5-HT, adenosine, Ach
• Analgesia at spinal and higher levels
• Altered function → hyperalgesia, neuropathic or chronic
pain

GABA = γ -aminobutyric acid; 5-HT = 5-hydroxytryptamine (serotonin); Ach = acetylcholine


Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:7–9.
Acute Pain: Mechanisms, Management, and Treatment Options

Role of Neuropeptides
Excitatory
• Substance P, neurokinin A
• ↑ Ca2+, induce sensitization, hyperalgesia
• Transsynaptic transmitters

Inhibitory
• Somatostatin, enkephalins, endorphins, dynorphins (?)
• Modulate intracellular cAMP, K+
• Act at µ , δ , κ opioid receptors

cAMP = cyclic adenosine monophosphate


Dougherty PM, Raja SN. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia;
1999:7–9.
Acute Pain: Mechanisms, Management, and Treatment Options

Role of Prostanoids in Pain


Acute Pain: Mechanisms, Management, and Treatment Options

Prostanoid Production by Cyclooxygenase (COX)

Arachidonic acid
Cyclooxygenase activity of COX

PGG2

Peroxidase activity of COX

PGH2

PGD2 PGF2 PGE2 PGI2 TXA2


α

PG = prostaglandin; TX = thromboxane
Acute Pain: Mechanisms, Management, and Treatment Options

Prostanoids and Their Physiologic Activities


Prostanoid
PGE2 Activities/Properties
• Produced in many organs, (eg, kidney,
intestinal tract)
• GI mucosal protection/repair
• Vasodilates
• Diuresis and natriuresis
• Inhibits inflammatory/ allergic cells

• ↑ platelet activation
• ↑ intravascular platelet aggregation
Thromboxane A2
• ↑ smooth muscle contraction in arteries and bronchi

• ↓ platelet aggregation
• Vasodilates
• ↑ renin release in kidney
Prostacyclin (PGI2)
Acute Pain: Mechanisms, Management, and Treatment Options

Treatment Options for Acute Pain


Acute Pain: Mechanisms, Management, and Treatment Options

WHO Analgesic Ladder


Fre
ed
Op can om fr
ioid ce om
to s for m r pain
± N evere oder
a
± Aon-op pain te
dju ioid
van
Pa
in
t 3
Op or pers
ioid inc i
for rea sting
mo m sin
d i l g
± N erat d to
e
± Aon-o pain
p
dj u i oi d
Pa van
in t
or p e
inc rsis 2
rea tin
sin g
No g
± n-op
Ad i
juv oid
an
t

World Health Organization, 1990. Used with permission.


Acute Pain: Mechanisms, Management, and Treatment Options

Analgesic Options for Acute Pain Management

• Opioid analgesics
• Nonopioid analgesics
– acetaminophen
– tramadol
– anti-inflammatory agents
• Combination analgesic products
• Local anesthetics, nerve, neuraxial blocks
Acute Pain: Mechanisms, Management, and Treatment Options

Opioid Analgesics
• Binding at µ , δ , κ receptors
• Highly efficacious
• May be combined with anti-inflammatory agents
• Effects may be reversed
• Side effects common
• Pain recurrence

Fishman SM, Borsook D. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional
Anesthesia; 1999:51–54.
Acute Pain: Mechanisms, Management, and Treatment Options

Adverse Effects of Opioids

• CNS depression, sedation


• Respiratory depression
• ↓ GI motility, nausea, vomiting
• Urinary retention
• Pruritus
Acute Pain: Mechanisms, Management, and Treatment Options

Nonopioid Analgesics

Acetaminophen Tramadol

Mechanism ↑ pain threshold • µ -receptor binding


of action • inhibits re-uptake of
norepinephrine and
serotonin (5-HT3)

Adverse effects Hepatotoxic Opioid-like effects

Sisson CB. In: Benzon HT, et al, eds. Essentials of Pain Medicine and Regional Anesthesia; 1999:59–62.
Acute Pain: Mechanisms, Management, and Treatment Options

Anti-inflammatory Agents
• Inhibit cyclooxygenase (COX), key enzyme in prostaglandin
synthesis
• Conventional anti-inflammatory analgesics inhibit both COX-
1 and COX-2 isoenzymes
• COX-1 inhibition → gastrotoxicity, ↓ platelet aggregation
• Some newer agents target COX-2 but do not inhibit COX-1 at
full therapeutic doses (specific cox-2 inhibitor, the COXIBS,
e.g. Celecoxib, the savest anti inflamatory agents in this
decade, that effective also as pain killer).
Acute Pain: Mechanisms, Management, and Treatment Options

Combination Analgesic Products

• Usually two or more agents with different yet


complementary mechanisms of action
• Severity of dose-related side effects may be reduced,
since lower doses of each agent are utilized
• Range of side effects increased
Acute Pain: Mechanisms, Management, and Treatment Options

Local Anesthetics, Nerve, Neuraxial Blocks

• Na+ channel blockade


• Possible interaction at pre- and postsynaptic junctions
• Tachyphylaxis
• Dose-related CNS, cardiovascular toxicity
Acute Pain: Mechanisms, Management, and Treatment Options

Nonpharmacologic Treatment Options for Pain


Cognitive-Behavioral
• Relaxation
• Preparatory information
• Imagery
• Hypnosis
• Biofeedback
Physical Agents
• Application of superficial heat and cold
• Massage
• Exercise
• Immobilization (eg, to provide rest and maintain
alignment after musculoskeletal procedures)
• Electroanalgesia (eg, TENS)
• Chiropractic
• Acupuncture

Carr DB, et al. AHCPR Pub. No. 92-0032. 1992.


Acute Pain: Mechanisms, Management, and Treatment Options

Other Approaches
Acute Pain: Mechanisms, Management, and Treatment Options

Multimodal Analgesia
An Example

Morphine
• Reduced doses of each
analgesic
• Improved antinociception due
to synergistic/additive effects
Potentiation
• May reduce severity of side
effects of each drug

NSAID,
acetaminophen,
nerve blocks

Kehlet H, Dahl JB. Anesth Analg. 1993;77:1048–1056.


Acute Pain: Mechanisms, Management, and Treatment Options

New Approaches to Treatment of Acute Pain

• Bradykinin receptor antagonist


• COX-2 specific inhibition
• Cytokine suppressive anti-inflammatory agents
(CSAIDs)
• Neuropeptide inhibitors
• Epibatidine analogues

Rang HP, Urban L. Br J Anaesth. 1995;75(2):145–156.


Acute Pain: Mechanisms, Management, and Treatment Options

Acute Pain Services


Acute Pain: Mechanisms, Management, and Treatment Options

Management of Surgical Pain


The Unmet Needs

• Pain is undertreated
• Inadequate knowledge of pain management
• Inadequate pain assessment

Rawal N. Anesth Pain Med. 1999;24(1):68–73.


Sinatra R. In: Cousins MJ, Bridenbaugh PO. Neural Blockade in Clinical Anesthesia and Management of
Pain; 1998:793–835.
American Pain Society Quality Improvement Committee. JAMA. 1995;1847–1880.
Acute Pain: Mechanisms, Management, and Treatment Options

Acute Pain Services


Goals
• Improve management of surgical pain
• Promote continuing education and training of healthcare
providers
• Increase awareness of importance of effective pain
management
• Serve as clinical research center

Chin ML. In: Ashburn MA, Rice LJ, eds. The Management of Pain; 1998:537–545.
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options
Acute Pain: Mechanisms, Management, and Treatment Options