Overview of Cancer Pain Syndromes

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Overview of cancer pain syndromes

AUTHORS: Russell K Portenoy, MD, Lara K Dhingra, PhD
SECTION EDITOR: Janet Abrahm, MD
DEPUTY EDITOR: Melinda Yushak, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Feb 21, 2022.
INTRODUCTION
Pain is an unpleasant sensory and emotional experience that affects most aspects of life,
including physical functioning, daily activity, psychologic and emotional status, and social
life. Pain is a complex symptom and there is substantial heterogeneity in how it is
experienced and in how it is manifested ( table 1).
In many cases, the constellation of symptoms and signs can suggest a specific cancer pain
syndrome [1]. The identification of such a syndrome may help to elucidate the etiology of the
pain, direct the diagnostic evaluation, clarify the prognosis for the pain or the disease itself,
and guide therapeutic intervention.
Cancer pain syndromes can be broadly characterized as acute or chronic. Acute pain
syndromes usually accompany diagnostic or therapeutic interventions, whereas chronic pain
syndromes usually are directly related to the neoplasm itself or to an antineoplastic therapy.
This topic review will provide an overview of acute and chronic cancer pain syndromes.
Cancer pain assessment is discussed elsewhere. (See "Assessment of cancer pain".)
ACUTE PAIN SYNDROMES
Most acute cancer pain syndromes are iatrogenic, ie, related to a diagnostic test or
treatment ( table 2) [1]. However, some are disease-related, such as pain due to acute
hemorrhage into a tumor, bone pain from a pathologic fracture, and visceral pain from acute
obstruction or perforation of a hollow structure ( table 3).
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Analgesic management of these acute pain syndromes is discussed in the following topics:
● "Breakthrough pain" is typically defined as a transient flare of moderate to severe pain

occurring on a background of chronic pain that is adequately controlled by an opioid
regimen [2]; this flare of pain is typically short lived and is usually related directly to the
cancer, a cancer treatment, or a diagnostic test. The management of breakthrough pain
is discussed elsewhere. (See "Cancer pain management with opioids: Optimizing
analgesia", section on 'Management of breakthrough pain'.)
● In patients receiving chronic opioid therapy for persistent cancer pain, the term
"breakthrough pain" is not used to describe singular events of acute, severe, and
longer lasting pain that occur after surgery or after an injury, whether or not the pain is
related to the cancer (eg, pathologic bone fracture). The management of this sort of
severe acute pain is similar to that for patients who are receiving long-term opioids for
chronic non-cancer pain. (See "Management of acute pain in the patient chronically
using opioids for non-cancer pain".)
Directly related to cancer — Acute pain syndromes that are directly related to the tumor
may necessitate urgent treatment of the underlying lesion, in addition to aggressive pain
control.
● Hemorrhage into a tumor – The prototype for this type of pain is bleeding into a site
of hepatocellular carcinoma (HCC). This is typically accompanied by severe right upper
quadrant pain, and is a potentially life-threatening complication, if the tumor ruptures.
Urgent intervention for control of bleeding may be needed, in addition to transfusion
and pain control. If measures such as transarterial embolization are unsuccessful,
emergency surgery may be required. (See "Clinical features and diagnosis of
hepatocellular carcinoma", section on 'Clinical features'.)
● Pathologic fracture – A pathologic fracture is a bone fracture that occurs within a

preexisting lesion such as a skeletal metastasis or a primary bone tumor. (See "Clinical
presentation and evaluation of complete and impending pathologic fractures in
patients with metastatic bone disease, multiple myeloma, and lymphoma".)
Patients describe the sudden onset of back or limb pain, with or without antecedent
trauma. Surgical stabilization of long bone fractures, if feasible and consistent with the
overall goals of care, may relieve pain and should be considered. Vertebral collapse may
be treated conservatively with analgesics or with an intervention, specifically
vertebroplasty or kyphoplasty; surgery is typically considered only rarely and typically
to address associated neurologic impairment. Radiation therapy (RT) is usually
considered for all pathologic fractures and often augments pain control over a period
of weeks or longer. (See "Radiation therapy for the management of painful bone
metastases".)
● Obstruction/perforation of a hollow viscus – Obstruction of a bile duct, ureter, or

bowel lumen by an intraabdominal or pelvic cancer or retroperitoneal fibrosis can also
present with acute severe pain. Relief may be obtained urgently through percutaneous
decompression, stenting, or occasionally surgery. (See "Supportive care for locally
advanced or metastatic exocrine pancreatic cancer" and "Clinical manifestations and
diagnosis of urinary tract obstruction (UTO) and hydronephrosis" and "Clinical
manifestations and diagnosis of retroperitoneal fibrosis" and "Management of small
bowel obstruction in adults".)
● Superior vena cava obstruction – Superior vena cava obstruction due to a tumor in
the mediastinum presents with some combination of facial and neck swelling, dyspnea,
dilated neck and chest wall veins, neck pain, or headache. Treatment usually involves
administration of a glucocorticoid and urgent RT, with or without endovenous
recanalization. (See "Malignancy-related superior vena cava syndrome".)
● Pain due to acute thrombosis – Deep venous thrombosis, most often in an extremity,
is a relatively common complication of cancer and is usually associated with pain and
swelling in the limb. (See "Risk and prevention of venous thromboembolism in adults
with cancer" and "Anticoagulation therapy for venous thromboembolism (lower
extremity venous thrombosis and pulmonary embolism) in adult patients with
malignancy".)
Associated with antineoplastic treatments — Acute pain can be associated with all types
of antineoplastic therapy, including chemotherapy, hormonal therapy, immunotherapy, and
RT ( table 4). Pain is highly prevalent during treatment, and the likelihood of significant
treatment-associated pain varies with the disease and its treatment. A systematic reviewed
not a pooled prevalence rate of 40 percent during cancer treatment across all treatments
and conditions [3].
Oral mucositis — The most common acute painful disorder associated with antineoplastic
therapy is oral mucositis [4]. Many types of systemic chemotherapy can result in this
complication, as can radiation to the head and neck region. Chemotherapy-associated
mucositis can affect the mucosa throughout the entire gastrointestinal tract, but pain most
often results from oral mucositis (stomatitis). Oral mucositis typically becomes clinically
evident during the first week after chemotherapy administration and evolves over weeks
after the start of fractionated RT. (See "Oral toxicity associated with systemic anticancer
therapy" and "Management and prevention of complications during initial treatment of head
and neck cancer".)
The incidence of chemotherapy-induced oral mucositis varies with the drug regimen and
dose, the use of concurrent therapies (especially RT), and host factors:
● High doses of chemotherapy that are part of a conditioning regimen for hematopoietic
stem cell transplantation cause noninfectious mucositis in approximately 70 percent of
patients by killing cells with high mitotic rates. Ulceration of the oropharyngeal mucosa
begins several days following initiation of the conditioning regimen. Initial symptoms
may consist of mild or moderate burning discomfort, but this often progresses to the
point where mucositis interferes with talking, eating, and swallowing. Significant pain
requiring opioid use persists in one-half of patients at three weeks after transplant.
(See "Early complications of hematopoietic cell transplantation", section on 'Oral
mucositis'.)
● Standard doses of many common chemotherapeutic agents can also cause mucositis
( table 5). Newer targeted therapies, such as mammalian target of rapamycin (mTOR)
inhibitors (eg, everolimus) and small molecule inhibitors of the vascular endothelial
growth factor receptor (eg, sorafenib, regorafenib), can also cause painful stomatitis.
The frequency and severity are both drug- and dose-dependent. The three most
commonly used cytotoxic agents associated with oral mucositis are doxorubicin,
fluorouracil (FU), and methotrexate. (See "Oral toxicity associated with systemic
anticancer therapy", section on 'Mucositis' and "Non-cardiovascular toxicities of
molecularly targeted antiangiogenic agents", section on 'Oral toxicity'.)
● Mucositis develops in nearly all patients receiving RT to the head and neck region. RT-
induced mucositis is similar qualitatively to that induced by chemotherapy. It usually
develops two to three weeks after starting treatment. The Incidence and severity of RT-
induced mucositis depend on the field, total dose and duration of RT, and the use of
concomitant chemotherapy.
Although newer RT approaches such as three-dimensional conformal RT (3D-CRT) and

intensity-modulated RT (IMRT) may reduce the incidence, mucositis remains a common
problem in patients treated for head and neck cancer. (See "Management of late
complications of head and neck cancer and its treatment" and "Management and
prevention of complications during initial treatment of head and neck cancer", section
on 'Mucositis'.)
● Pain due to mucositis may be more severe or prolonged when the ulcers become
superinfected with bacteria or fungus, and in the setting of graft-versus-host disease.
(See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host
disease".)
Numerous treatment strategies for established mucositis have been studied, as have several
preventive strategies.
A year 2020 evidence-based review by the Multinational Association of Supportive Care in

Cancer and the International Society of Oral Oncology [5] offers specific guidelines, which
are discussed in more detail elsewhere. (See "Oral toxicity associated with systemic
anticancer therapy".)
Chemotherapy-induced neuropathy — Many chemotherapeutic agents are neurotoxic.

Acute neuropathic pain in patients treated with chemotherapy may manifest as a
polyneuropathy, or less commonly, a mononeuropathy.
Chemotherapy-related polyneuropathy was first described in patients treated with the vinca
alkaloid vincristine. Other agents with a high incidence of polyneuropathy include cisplatin,
paclitaxel, oxaliplatin, thalidomide, and bortezomib [6]. All of these drugs can produce acute
paresthesias and dysesthesias. Although they can present acutely (eg, oxaliplatin-induced
pharyngolaryngeal spasm), the onset of pain associated with neuropathy in patients treated
with these agents is more often insidious. (See "Overview of neurologic complications of
conventional non-platinum cancer chemotherapy" and "Overview of neurologic
complications of platinum-based chemotherapy", section on 'Acute neurotoxicity'.)
Chemotherapy-induced neuropathic pain usually gradually improves after the treatment is

stopped or the dose is reduced; occasionally, neuropathic pain becomes chronic. (See
'Chemotherapy-related neuropathy' below.)
Rare overall, acute chemotherapy-related mononeuropathy is best described with vincristine.

Orofacial pain (particularly jaw pain) is the most common manifestation, with multiple sites
affected in the distribution of the trigeminal and glossopharyngeal nerves [7]. Other nerves,
including the recurrent laryngeal, optic, and auditory nerves, may also be affected.
Other chemotherapy-related acute pain syndromes — Specific chemotherapeutic agents

and hormone agents are associated with a variety of other acute pain syndromes, examples
of which are provided in the table ( table 6). Arthralgia or myalgia often accompanies
paclitaxel therapy and may occur with rapid glucocorticoid tapering (a syndrome known as
"pseudorheumatism"); bone pain may also occur during treatment with pegfilgrastim.
Painful rash on the palms and soles, a condition known as palmar-plantar erythrodysesthesia
syndrome, hand-foot syndrome, acral erythema, toxic erythema of the palms and soles, has
been associated with numerous drugs, including continuously infused fluorouracil,
capecitabine, vinorelbine, liposomal doxorubicin, docetaxel and paclitaxel, the tyrosine
kinase inhibitors sorafenib and sunitinib, high-dose methotrexate, and the mTOR inhibitor
everolimus. (See "Cutaneous adverse effects of conventional chemotherapy agents" and
"Cutaneous adverse events of molecularly targeted therapy and other biologic agents used
for cancer therapy".)
Intrathecal therapy for leptomeningeal metastatic disease, intraperitoneal therapy for

gynecologic tumors, intravesical therapy for bladder cancer, and hepatic intraarterial
injection of chemotherapy (typically hepatic transarterial chemoembolization) all can be
complicated by acute pain. When acute pain is anticipated, patient preparation, education,
and reassurance are important. (See "Treatment of leptomeningeal disease from solid
tumors" and "Intraperitoneal chemotherapy for treatment of ovarian cancer" and "Localized
hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for
local thermal ablation", section on 'TACE and bland particle embolization' and "Treatment of
primary non-muscle invasive urothelial bladder cancer".)
Radiation therapy-induced bone pain — Approximately one-third of patients undergoing

RT to a bone metastasis will experience an acute increase in focal bone pain [8]. This pain is
transitory, but if severe, it may necessitate treatment with an opioid or a short course of an
oral glucocorticoid. (See "Radiation therapy for the management of painful bone
metastases", section on 'Time course of relief and incidence of pain flare'.)
Radiation plexopathy — An acute, transient brachial plexopathy can occur after RT that
involves a nerve plexus ( table 4) [9]. Mimicking the syndrome known as acute brachial
plexitis (brachial neuritis), this disorder is characterized by pain, paresthesias, and weakness
in the shoulder, arm, and hand. The syndrome is usually self-limited but may cause
persistent pain or dysfunction. Newer methods of RT appear to have substantially reduced
the incidence of this condition. (See "Brachial plexus syndromes" and "Lumbosacral plexus
syndromes".)
Radiation enteritis and proctitis — Patients undergoing abdominal irradiation may

experience cramping, nausea, and vomiting (radiation enteritis). The corresponding
syndrome in those receiving pelvic irradiation (radiation proctitis) includes painful tenesmus
with diarrhea, mucus discharge, and bleeding. Newer RT methods such as 3D-CRT have
reduced the incidence and severity of these painful syndromes, but they have not eliminated
the risk of bowel toxicity when the RT field includes the intestinal viscera. (See "Overview of
gastrointestinal toxicity of radiation therapy", section on 'Enteritis' and "Radiation proctitis:
Clinical manifestations, diagnosis, and management".)
Symptoms can occur within hours after the onset of RT, but they more often develop several
weeks into therapy. Specific factors that increase the risk for RT-related bowel toxicity include
older age, concomitant chemotherapy, and at least in the setting of rectal cancer, the use of
postoperative rather than preoperative RT. (See "Neoadjuvant therapy for rectal
adenocarcinoma", section on 'Indications for neoadjuvant treatment'.)
CHRONIC PAIN SYNDROMES
Approximately three-fourths of cancer patients who have chronic pain have nociceptive
(somatic or visceral) or neuropathic syndromes that represent direct effects of the neoplasm
( table 7) [1]. (See "Assessment of cancer pain", section on 'Inferred pathophysiology and
treatment implications'.)
Other causes of chronic pain in cancer patients are antineoplastic treatments ( table 8)
[10], and disorders that are unrelated to the disease or its treatment.
A significant barrier to better understanding chronic cancer pain syndromes, their

prevalence, and their consequences, is the lack of consistent diagnostic criteria for specific
syndromes. At present, they are classified according to the putative mechanism (ie, tumor
related, treatment related) and the underlying pathophysiology (ie, nociceptive [somatic,
visceral] or neuropathic). Consensus-based core diagnostic criteria for several cancer-related
pain syndromes, specifically bone pain, chemotherapy-induced peripheral neuropathy, and
pancreatic cancer-related pain, have been published [11].
Tumor-related somatic pain syndromes — Tumor involvement of bone, joints, muscle, or

connective tissue can cause persistent somatic pain ( table 7).
Multifocal bone pain — Bone metastases are the most prevalent cause of chronic pain in
cancer patients. Skeletal metastases are a common manifestation of distant disease spread
from many types of solid cancers, especially those arising in the lung, breast, and prostate.
(See "Epidemiology, clinical presentation, and diagnosis of bone metastasis in adults".)
The pain associated with bone metastases may be due to direct invasion, secondary
pathologic fracture, or damage to adjacent structures. Although the factors that convert a
painless to a painful bone metastasis are not known, it is now well accepted that bone pain,
once established, has both inflammatory and neuropathic components [12]. The neuropathic
component is presumably induced by direct nerve injury and consequent pathologic
sprouting of both sensory and sympathetic nerve fibers [13,14]. Presumably, some
combination of these neural changes, the complex perineural release of growth factors
and/or chemical mediators, and mechanical distortion related to microfracture culminates in
bone pain. Diagnostic criteria for cancer-induced bone pain have been developed ( table 9)
[11].
Local field external beam radiation therapy (RT) is a well-recognized and effective palliative
modality for painful bone metastases; pain relief is seen in 80 to 90 percent of cases. (See
"Radiation therapy for the management of painful bone metastases".)
Although the majority of patients with multifocal bone pain have widespread bony
metastases, hematologic malignancies can rarely produce painful bone marrow expansion
[15]. This is presumably caused by nests of rapidly growing cells in the marrow.
In addition, a rare paraneoplastic form of renal phosphate wasting called oncogenic

osteomalacia can cause osteomalacia, multifocal bone pain, and fractures [16]. This rare
syndrome is most often associated with mesenchymal neoplasms, and complete tumor
removal can lead to rapid correction of the biochemical derangements, remineralization of
bone, and symptom improvement. (See "Hereditary hypophosphatemic rickets and tumor-
induced osteomalacia", section on 'Tumor-induced osteomalacia'.)
● Vertebral pain syndromes – The most common sites of bone metastases are the
vertebrae. Specific syndromes may evolve from lesions involving different spinal levels
( table 10). Back pain that develops at any level from vertebral metastases may signal
epidural extension, which is associated with the serious complications of spinal cord or
cauda equina compression. (See "Clinical features and diagnosis of neoplastic epidural
spinal cord compression".)
Neoplastic epidural spinal cord compression (ESCC) is a common complication of solid

tumors [17]. Most often, ESCC is caused by posterior extension of a vertebral body
metastasis into the epidural space ( figure 1). ESCC almost always presents initially as
back or neck pain. Untreated, tumor growth may eventually cause irreversible loss of
neurologic function. Because pain usually precedes neurologic impairment by weeks or
months, it is crucial to diagnose epidural disease extension in patients when pain is the
sole complaint so that effective treatment may be started to prevent or retard the
progression of neurologic impairment. (See "Clinical features and diagnosis of
neoplastic epidural spinal cord compression", section on 'Clinical features'.)
In patients with metastatic disease, worsening spine pain, pain described as worse
when recumbent, pain that develops in a radicular distribution (eg, around the chest
wall or into the arm or leg), or pain associated with a neurologic symptom or sign
typically indicates the need for magnetic resonance imaging (MRI). Total spine MRI is
the preferred approach to evaluate for ESCC in the context of metastatic disease. (See
"Clinical features and diagnosis of neoplastic epidural spinal cord compression", section
on 'Diagnostic evaluation'.)
For most patients, RT represents first-line definitive treatment for ESCC. Although
multiple fraction RT has been considered the standard of care, there is no evidence that
outcomes are better among those with advanced illness than those obtained with
single-fraction therapy [18]; a single palliative dose of RT is an option for patients with
limited prognosis. Glucocorticoid treatment also is useful to temporarily improve pain
and neurologic functioning, often providing a window of time during which RT can be
provided. Surgical decompression is considered if the tumor type is typically

radioresistant and the lesion is high grade, if the neurologic status is deteriorating
during RT, if ESCC occurs in a previously irradiated field, if the lesion is posterior and
can be easily extirpated, or if a tissue diagnosis is needed. (See "Treatment and
prognosis of neoplastic epidural spinal cord compression".)
● Pelvic and hip metastases – Pelvic metastases may involve the ilium, ischium, pubis,
or sacroiliac areas. In addition to local pain, tumor invasion of the hip joint may present
as hip or inguinal pain upon walking or as pain in the knee or thigh. Injury to structures
just inside the pelvic ring can result in related syndromes, such as a malignant
piriformis syndrome (pain in the buttock and/or sciatic distribution, often with
exacerbation during internal rotation of the hip) or a painful plexopathy ( table 7).
(See "Overview of lower extremity peripheral nerve syndromes", section on
'Compression/trauma in the sciatic notch/gluteal region'.)
Sacral syndrome is associated with the destruction of the sacrum due to neoplastic
infiltration. It is characterized by severe focal pain radiating to the buttocks, perineum,
and posterior thigh. Involvement of the lateral hip rotators makes movement at the hip
painful.
These lesions are typically treated with RT, but interventional pain strategies or surgery
may be considered in some cases [19].
● Base of skull metastases – Neoplastic injury to the base of the skull may occur from
the local extension of a nasopharyngeal cancer or from skeletal metastases involving
this area, usually due to breast, lung or prostate cancers [20-22]. Depending on their
location, base of skull metastases may cause specific pain syndromes ( table 11). In
most situations, the responsible lesion is readily identifiable on axial CT imaging with
bone windows or MRI.
Soft tissue pain — Sarcomas can arise in muscle, as can metastases [23]. In either case,
pain at the local site of involvement is common.
Muscle pain may also be due to muscular cramps, which in cancer patients can be associated
with neural injury (eg, radiculopathy or plexopathy) or caused by a biochemical abnormality
[24]. Biochemical abnormalities such as hypercalcemia or hyponatremia may be the result of
a paraneoplastic syndrome (see "Causes of hypotonic hyponatremia in adults").
Treatment of cancer-associated muscle cramps is nonspecific and employs the same

approaches used to manage cramps in other disorders [25,26].
Somatic chest wall pain is common among patients with lung cancer or mesothelioma, and
can be due to direct tumor infiltration of the ribs, intercostal spaces, or parietal pleura
( table 7). The pain usually is worsened by deep inspiration or cough. A malignant
intercostal mononeuropathy may accompany this lesion and yield a syndrome that has
mixed nociceptive and neuropathic features.
Soft tissue pain may also be caused by a paraneoplastic disorder (eg, hypertrophic
osteoarthropathy). (See 'Paraneoplastic syndromes' below.)
Tumor-related visceral pain syndromes — Visceral pain can be caused by obstruction of

any hollow viscus or injury to another pain-sensitive visceral structure such as the visceral
pleura, hepatic capsule, or peritoneum ( table 7) [1]. These syndromes are particularly
common in patients with gastrointestinal and gynecologic malignancies.
● Hepatic distention syndrome – Pain-sensitive structures in the region of the liver

include the hepatic capsule, vessels, and biliary tract. Stretching of the hepatic capsule
by a primary hepatoma or intrahepatic metastases can cause chronic cancer pain,
which is commonly described as dull, right sided subcostal pain. If the superior aspect
of the capsule is involved, diaphragmatic irritation may lead to referred pain to the top
of the ipsilateral shoulder.
Pain also may result from injury or invasion of the porta hepatis, with or without biliary
duct obstruction. This pain may be referred to the ipsilateral scapular region.
● Midline retroperitoneal syndrome – Tumor invasion of the pancreas or other

subdiaphragmatic midline structures (eg, with retroperitoneal lymphadenopathy) may
produce pain by injuring the deep somatic tissues of the posterior abdominal wall or by
invasion of the celiac plexus [27-29]. Pain is experienced in the epigastrium, low
thoracic region of the back, or both. It is often described as a dull ache or a "boring"
pain that is worse when lying down and relieved by sitting up.
● Chronic intestinal obstruction – Diffuse abdominal pain may be related to chronic

intestinal obstruction from either an abdominal neoplasm or scarring. The common
cancers that cause intestinal obstruction are ovarian (up to 42 percent of cases) and
colorectal (up to 24 percent of cases) [30,31]. In such cases, pain may be related to
distension proximal to an obstructed bowel segment, mural ischemia, or tension on the
mesentery.
Pain may be continuous or colicky, and may be referred to the dermatomes

represented by the spinal segments supplying the affected viscera. Nausea, vomiting
and constipation are important associated symptoms. Abdominal radiographs taken in
both the supine and upright positions may demonstrate the presence of air-fluid levels
and intestinal distention. CT or MRI usually reveals the extent of the intraabdominal
neoplasm. (See "Large bowel obstruction" and "Etiologies, clinical manifestations, and
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diagnosis of mechanical small bowel obstruction in adults" and "Palliative care of bowel
obstruction in cancer patients".)
● Peritoneal carcinomatosis – Carcinomatous seeding of the peritoneum leads to

peritoneal inflammation, mesenteric tethering, malignant adhesions, and ascites, all of
which can cause pain. Cancers of the ovary, colorectum and stomach are frequent
causes of this syndrome. Pain may be diffuse or focal, sharp or crampy, and worse
postprandially. Abdominal distention, nausea and constipation are common. CT may
reveal evidence of ascites, omental infiltration, and/or peritoneal nodules [32]. (See
"Malignancy-related ascites".)
● Malignant perineal pain – Malignancy-related perineal pain is most often associated

with tumors of the colon or rectum, female reproductive tract, and distal genitourinary
system. The pain may be exacerbated by sitting or standing, and there may be a
component of tenesmus or tenesmoid pain, or intermittent severe pain consistent with
bladder spasms [33]. Some patients describe a discrete syndrome that is characterized
by discomfort or pain that occurs rapidly after standing and disappears in other
positions; this symptom complex mimics an idiopathic tension myalgia syndrome. (See
"Chronic pelvic pain in nonpregnant adult females: Causes".)
● Adrenal pain syndrome – Adrenal metastases (which are most commonly seen in non-
small cell lung cancer) can produce unilateral flank pain which may radiate into the
ipsilateral upper and lower quadrants of the abdomen [34]. Severe acute pain may
result from adrenal hemorrhage [35]. (See "Clinical presentation and evaluation of
adrenocortical tumors".)
● Ureteral obstruction – Gastrointestinal, genitourinary and gynecologic cancers are the

most common causes of ureteral obstruction [36]. Although these patients may present
acutely, others present subacutely with flank pain which radiates to the inguinal region.
Pain is often colicky, ie, intermittent and wave-like. When severe, pain due to ureteric
obstruction may be associated with nausea and vomiting. Imaging studies may confirm
the nature of the syndrome by demonstrating ipsilateral hydronephrosis. (See 'Directly
related to cancer' above and "Clinical manifestations and diagnosis of urinary tract
obstruction (UTO) and hydronephrosis".)
Tumor-related neuropathic pain — Neuropathic pain syndromes that are directly caused by
neoplastic invasion may involve the spinal cord, nerve roots, plexuses, or peripheral nerves
( table 7). Approximately 40 percent of patients with chronic cancer-related pain have a
neuropathic pain syndrome.
Leptomeningeal metastases — Any solid or hematologic neoplasm can potentially

infiltrate the leptomeninges, but the common tumors are lung and breast cancer, lymphoma
and leukemia [37,38]. (See "Clinical features and diagnosis of leptomeningeal disease from
solid tumors".)
Clinical presentation is variable:
● Some patients have headache, which may or may not have characteristics typical for
intracranial hypertension (generalized aching or throbbing that is worse in the morning
and with Valsalva maneuvers, and sometimes associated with nausea and vomiting).
(See "Evaluation and management of elevated intracranial pressure in adults".)
● Others experience nonspecific back pain, or pain in a radicular distribution that can
affect any level of the neuraxis.
● These variable pains may be accompanied by an equally diverse set of neurologic

complications, including seizures, cognitive impairment, hemiparesis or hemisensory
syndromes, spinal cord syndromes, or any combination of motor or sensory
disturbance consistent with a cranial neuropathy or radiculopathy.
Given the variable presentation, leptomeningeal metastases can mimic any type of pain
syndrome or neurologic disorder, and should be suspected whenever pain or neurologic
impairment progresses and eludes initial diagnosis.
The diagnosis of a leptomeningeal neoplasm is made by the finding of malignant cells on

lumbar puncture. T1-weighted, gadolinium-enhanced cranial and spinal cord MRI may
identify or raise suspicion for leptomeningeal spread, and can be positive even if the
cerebrospinal fluid is initially negative. (See "Clinical features and diagnosis of
leptomeningeal disease from solid tumors", section on 'Diagnostic evaluation'.)
Cranial neuralgias — Malignancy-related cranial neuralgias can develop from metastases

involving the base of the skull or the leptomeninges, or from cancers that arise in the soft
tissue of the head, neck, or sinuses [39].
● Glossopharyngeal neuralgia – Glossopharyngeal neuralgia is characterized by

paroxysmal unilateral severe, stabbing or lancinating pain in the throat or neck which
may radiate to the ear and mastoid regions. Typical triggers include chewing,
swallowing, coughing, speaking, yawning, certain tastes, or touching the neck or
external auditory canal. The syndrome can occur in a pattern of episodes lasting weeks
to months, alternating with longer periods of remission.
Injury to the ninth cranial nerve is most often caused by leptomeningeal metastases, or
from primary tumors or metastatic deposits that involve the jugular foramen. (See
"Overview of craniofacial pain", section on 'Glossopharyngeal neuralgia'.)
● Trigeminal neuralgia – A syndrome that mimics idiopathic trigeminal neuralgia may

be caused by tumors of the middle or posterior cranial fossa. This pain may be labeled
a painful trigeminal neuropathy. However, because it most often presents with "electric
shock-like" or stabbing paroxysms that are similar to the symptoms seen in the
idiopathic syndrome, it may be called a malignant, or tumor-related, trigeminal
neuralgia. If a lesion that involves the trigeminal nerve produces different qualities of
pain, such as a constant aching or burning in the face, it is more appropriate to
describe the syndrome as a painful trigeminal neuropathy rather than a malignant
trigeminal neuralgia. (See "Trigeminal neuralgia", section on 'Clinical features'.)
Many patients with tumor-related trigeminal neuralgia are treated, at least initially, for
an idiopathic process. Over time, however, tumor growth leads to symptoms and signs
that raise suspicion as to the nature of the disorder (eg, change in the quality of the
pain or the development of neurologic deficits on examination) [40]. Imaging of both
the brain and skull base may be necessary to characterize or exclude a mass lesion as
the cause of the pain and associated features. (See "Trigeminal neuralgia", section on
'Mechanisms'.)
Radiculopathies — Any malignant process that compresses, distorts, or inflames nerve

roots may cause a painful radiculopathy. If multiple nerve roots are affected, it is called a
polyradiculopathy. A painful radiculopathy may result from leptomeningeal metastases,
intradural tumor (particularly meningioma, neurofibroma, and ependymoma) or tumor in
the epidural space. The latter situation is most common and may arise via posterior
extension of a tumor from a vertebral body metastasis, or growth into the intervertebral
foramen from a paraspinal site of disease ( figure 1). (See "Acute lumbosacral
radiculopathy: Etiology, clinical features, and diagnosis".)
Radicular pain may be continuous or intermittent, aching or sharp, or dysesthetic (eg,

burning or electrical-like) in quality; it may or may not be associated with neurologic signs.
When located in the thoracic level and bilateral in distribution, the pain may be experienced
as a tight band across the chest or abdomen, a presentation that signals a relatively high
likelihood of associated epidural disease. (See "Clinical features and diagnosis of neoplastic
epidural spinal cord compression", section on 'Pain'.)
A high index of suspicion for a malignant cause of radiculopathy or polyradiculopathy should

lead to a spinal MRI. If the patient has known vertebral metastasis or paraspinal disease, this
test can be done without contrast enhancement; if infiltration of nerve roots is suspected,
then a study with and without the injection of contrast is more informative.
Plexopathies — Tumor-related plexopathies may involve the cervical, brachial, or

lumbosacral plexus ( table 12) [41]. Pain is the usual presenting symptom.
● Cervical plexopathy – A malignant cervical plexopathy may be due to a head and neck
tumor, or to metastatic deposits that originate in the cervical lymph nodes. The pain,
which is often described as aching or burning, may be experienced in the periauricular,
postauricular, or anterior regions of the neck, or be referred to the lateral aspect of the
face, head or shoulder.
If there is involvement of the superior cervical (stellate) ganglion of the sympathetic

chain or of the sympathetic nerves adjacent to the carotid artery, Horner syndrome
(ipsilateral miosis, ptosis, and anhidrosis) may be present. (See "Horner syndrome".)
● Brachial plexopathy – Brachial plexopathy may present with shoulder, arm or hand
pain, with or without neurologic deficits or Horner syndrome.
The usual cause of a malignant brachial plexopathy is local extension of a primary or

metastatic tumor; cancers of the lung or breast, and lymphomas are the most common
etiology [41]. Primary brachial plexus tumors, such as schwannomas or neurofibromas,
are uncommon, and most occur as solitary tumors. These rarely cause symptomatic
plexopathies. However, multiple tumors occur in patients with neurofibromatosis type
1, and these are more likely than solitary tumors to present with pain or clinical deficits.
Initial signs and symptoms vary based on anatomic location (see "Brachial plexus
syndromes"):
• When the inferior plexus is involved first, as occurs with tumors of the lung arising
in the region of the superior sulcus (Pancoast tumors), pain typically begins in the
elbow and gradually spreads to involve the medial arm and hand. (See "Superior
pulmonary sulcus (Pancoast) tumors".)
• When the superior aspect of the plexus is injured first, as occurs when tumor arises
from cervical lymph nodes and grows inferiorly, the pain typically starts in the
shoulder.
The pain is classically followed by paresthesias in the distribution innervated by the

involved nerves ( figure 2). Weakness and sensory loss follow. Ultimately, a
panplexopathy may develop, with pain and dysfunction that affects the entire limb.
Among patients who have been previously treated for a malignancy, the differential
diagnosis of a new brachial plexopathy includes recurrent tumor and radiation injury. In
the setting of a known neoplasm and RT, distinguishing between cancer recurrence and
radiation-induced plexopathy can be challenging. (See "Brachial plexus syndromes",
section on 'Radiation-induced' and 'Postradiation pain syndromes' below.)
The diagnosis of neoplastic versus radiation-induced brachial plexopathy is suggested

by the symptoms and signs, and electrodiagnostic findings, and is confirmed by
imaging, or in some cases, by biopsy. In general, radiation-induced plexopathy is less
painful than neoplastic brachial plexopathy; the upper plexus is more commonly
involved, there often is relatively intense paresthesias, and radiation changes in the
skin and other soft tissues are evident (eg, poikiloderma, telangiectasias, atrophy,
hyperpigmentation, and lymphedema). Radiation is less likely to be associated with
Horner syndrome than plexopathy related to tumor recurrence.
The diagnosis of a radiation-induced rather than neoplastic plexopathy is supported by

the presence of so-called myokymic discharges on electromyography. These are
relatively specific for radiation-induced injury, but are not a universal feature, and their
absence does not exclude the diagnosis.
MRI or CT scan of the plexus can usually establish the diagnosis. Occasionally, biopsy is
needed. Because tumors adjacent to the spine may be responsible for a brachial
plexopathy, MRI of the epidural space may be needed. Imaging of the chest by CT or
MRI is most useful to detect a pulmonary tumor.
● Celiac plexus – Tumor invasion of the celiac plexus, most notably by pancreatic cancer,
is commonly associated with intense and often refractory midepigastric pain, which has
been labeled the midline retroperitoneal syndrome. Diagnostic criteria for this
syndrome have been proposed ( table 13) [8]. The pain is often described as gnawing
and radiates bilaterally under the ribs and into the midback. This pain is attributed to
local tumor growth and the proximity of tumors to the celiac plexus. (See "Supportive
care for locally advanced or metastatic exocrine pancreatic cancer", section on 'Pain'.)
● Lumbosacral plexopathy – Malignant lumbosacral plexopathy is primarily associated

with colorectal, cervical, and breast cancers, sarcomas, lymphomas, and sacral
chordomas. Neoplastic invasion typically presents with severe and progressive pain.
The distribution of the pain and associated signs and symptoms depends on the site of
anatomic involvement ( table 12).
The diagnostic evaluation of a patient with a lumbosacral plexopathy is described in

detail elsewhere. (See "Lumbosacral plexus syndromes".)
Peripheral mononeuropathies — Painful peripheral mononeuropathies can result from

direct tumor invasion of a peripheral nerve [41]. A classic example is malignant intercostal
neuropathy complicating a chest wall tumor.
Paraneoplastic syndromes — Paraneoplastic syndromes are a heterogeneous group of

disorders in cancer patients that are caused by substances released by a tumor or produced
in reaction to it. These substances can be hormones or other compounds, including
antibodies or other compounds produced through immune responses. Paraneoplastic

disorders are not caused by direct tumor invasion, metabolic and nutritional deficits,
infections, coagulopathy or side effects of cancer treatment.
Paraneoplastic syndromes most commonly affect the nervous system, but they can affect
many tissues. Approximately 40 percent of paraneoplastic neuropathies are associated with
pain [42]. Some examples of painful paraneoplastic syndromes are outlined in the table
( table 14), and two are described in more detail below:
● Subacute sensory neuronopathy – One of the best characterized painful neurologic

paraneoplastic syndromes is subacute sensory neuronopathy (sensory
ganglionopathy), a rare condition that is related to inflammation of the dorsal root
ganglion. Like many other neurologic paraneoplastic syndromes, it is most common in
patients with small cell lung cancer.
The sensory deficits typically begin with loss of vibratory sensation and joint position
sense following by impairment in pain and temperature sensation. Patients frequently
complain of the sensation of "pins and needles" or "electric shocks." The symptoms may
initially affect one extremity but, in a few weeks or months, they usually progress to
involve other extremities, the face, abdomen, or trunk. A severe sensory ataxia may
prevent walking or even self-care. In a subset of patients, hyperalgesia and
spontaneous pain remain the prominent symptom, and sensory ataxia is mild or even
absent. (See "Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and
muscle", section on 'Subacute sensory neuronopathy'.)
Other, more prevalent paraneoplastic polyneuropathies comprise axonopathies that

may accompany any tumor type but are often associated with plasma cell dyscrasias.
The pain associated with these types of neuropathy begins in the feet symmetrically
and gradually ascends as the lesion progresses. All of these paraneoplastic
neuropathies can be the initial manifestation of an underlying malignancy and their
occurrence should prompt a search for an occult cancer. (See "Paraneoplastic
syndromes affecting spinal cord, peripheral nerve, and muscle", section on 'Chronic
sensorimotor neuropathy'.)
● Hypertrophic osteoarthropathy – Hypertrophic osteoarthropathy is a syndrome

characterized by abnormal proliferation of the skin and osseous tissue at the distal
parts of the extremities. The secondary form is usually associated with lung cancer.
Clinical features include digital clubbing ( figure 3), periostosis of tubular bones
( image 1 and image 2), and synovial effusions, which are most prominent in the
large joints. Periostosis is usually accompanied by pain on palpation of the involved
area. Some patients present with a painful arthropathy in advance of clubbing. (See
"Malignancy and rheumatic disorders", section on 'Hypertrophic osteoarthropathy'.)
Headache — A new, changed, or progressive headache in a patient with a history of cancer

should be evaluated first with a thorough neurologic examination, and then with imaging
studies if the diagnosis of an intracranial mass lesion is suspected. (See "Evaluation of
headache in adults".)
Chronic pain related to antineoplastic treatments — Chemotherapy (including

glucocorticoid therapy, hormonal therapy, cytotoxic therapy, and biologic agents), RT, and
surgery each may be associated with a group of chronic pain syndromes ( table 8). As a
result of these syndromes, chronic pain is one of the most common and troubling conditions
among cancer survivors [43-45].
Chemotherapy-related neuropathy — Although painful peripheral neuropathy resulting

from cytotoxic therapy usually subsides over time, some patients develop persistent chronic
pain (see "Prevention and treatment of chemotherapy-induced peripheral neuropathy",
section on 'Chronic neurotoxicity'). Diagnostic criteria for chemotherapy-induced peripheral
neuropathic pain have been proposed ( table 15).
The pain is similar to other axonopathies, with initial involvement of the feet and distal legs,
followed by the hands and arms. The severity of the pain, and the presence and degree of
neurologic impairment vary widely depending on the agent to which the patient was
exposed and the dose. (See "Overview of neurologic complications of platinum-based
chemotherapy" and "Overview of neurologic complications of conventional non-platinum
cancer chemotherapy".)
Occasionally, patients develop a persistent Raynaud phenomenon; this has been observed in
approximately one-third of cancer patients with testicular tumors treated with regimens
containing cisplatin, vincristine, and bleomycin. (See "Treatment-related toxicity in testicular
germ cell tumors", section on 'Raynaud phenomenon'.)
Bone complications and glucocorticoids — Chronic use of glucocorticoids may cause

avascular necrosis of the femoral or humeral head, which is typically heralded by a painful
arthropathy. Radiologic changes on MRI or CT studies may not appear for a few months after
the initial report of pain.
Steroids also accelerate osteoporosis, which may predispose to vertebral compression

fractures associated with acute or chronic back pain. (See "Major adverse effects of systemic
glucocorticoids", section on 'Bone and muscle effects'.)
Antiandrogens and gynecomastia — Painful gynecomastia develops in the majority of

males receiving therapy for antiandrogens alone for advanced prostate cancer unless
prophylactic RT is administered. (See "Side effects of androgen deprivation therapy", section
on 'Gynecomastia'.)
Postsurgical pain syndromes — Well-defined pain syndromes may occur after the surgical
excision of cancer. The best characterized include postmastectomy pain syndrome, post-
radical neck dissection pain syndrome, post-thoracotomy pain syndrome, postoperative
frozen shoulder, postsurgery pelvic floor pain, stump and phantom limb pain following
amputation, and phantom breast pain ( table 16). These syndromes are predominantly
neuropathic and presumably related to nerve injury at the time of surgery. (See
"Management of late complications of head and neck cancer and its treatment" and
"Mastectomy", section on 'Pain' and "Mastectomy", section on 'Phantom breast syndrome'.)
Pain and phantom sensation after limb amputation — Chronic pain following limb
amputation may involve stump pain, phantom pain, or both. Stump pain may be due to
neuroma formation several months after amputation, but a poorly fitting prosthesis,
recurrent tumor, infection, or ischemia also may contribute [46].
Phantom sensation, the sensory experience that the amputated limb is still present, occurs
in most amputees. Phantom pain, which is often paroxysmal and atypical, and described by
some as an intense twisting or crushing sensation, is also common [47]. (See "Lower
extremity amputation", section on 'Phantom limb pain' and "Upper extremity amputation",
section on 'Phantom limb pain'.)
Numerous neurophysiologic explanations for phantom pain have been advanced, from
changes at the stump to functional cortical changes. Sensory deafferentation in primates
and arm amputation in humans causes cortical somatosensory reorganization; this
phenomenon may explain the elicitation of phantom pain by sensory stimulation at other
sites [48].
There is limited evidence that mirror therapy, motor imagery, and virtual visual feedback
reduce phantom limb pain [49]. The evidence in favor of mirror therapy appears to be the
strongest [50]. There is also emerging support for the efficacy of transcranial stimulation, in
particular transcranial magnetic stimulation [51]. There is only low-quality evidence
supporting several drug therapies, including gabapentin, ketamine, and morphine [52].
Postradiation pain syndromes — Chronic pain following RT is a late complication and often
must be differentiated from recurrent tumor.
Plexopathies — Radiation-induced cervical, brachial or lumbosacral plexopathies may

occur months to many years after RT [41,53]. The usual presenting signs are weakness and
sensory changes. Although they cause pain, it is rarely severe. Chronic perineal pain
following pelvic RT is often clinically associated with a sacral plexopathy. The pain is burning
in nature and may extend anteriorly to the vagina or scrotum [54].
The incidence of these syndromes has declined over the years due to lower-dose regimens
and better RT techniques. (See "Brachial plexus syndromes", section on 'Neoplastic and
radiation-induced brachial plexopathy' and "Lumbosacral plexus syndromes", section on

'Radiation plexopathy'.)
The main differential is with a plexopathy from recurrent tumor. As noted above, in the
setting of a known neoplasm and RT, distinguishing between cancer recurrence and
radiation-induced brachial plexopathy can be challenging. These issues are discussed above.
(See 'Plexopathies' above.)
Myelopathy — Chronic radiation myelopathy is another late complication which may

develop many years following the completion of RT. Sensory symptoms, including pain,
typically precede the development of progressive motor and autonomic dysfunction. The
pain is usually characterized as a burning dysesthesia and is localized to the area of spinal
cord damage or below this region. The neurologic findings may be consistent with a
transverse myelopathy, sometimes in a Brown-Sequard pattern. (See "Complications of
spinal cord irradiation", section on 'Late radiation-induced myelopathy' and "Anatomy and
localization of spinal cord disorders", section on 'Brown-Sequard (hemicord) syndrome'.)
Gastrointestinal tract — Chronic enteritis and proctitis may result from irradiation to the
abdomen and pelvis. Small bowel obstruction, strictures, gastroparesis and intestinal
pseudo-obstruction (eg, impaired gastrointestinal motility without any anatomical
obstruction), fistula formation, gastrointestinal perforation, and bleeding are all late
manifestations of radiation toxicity to the gastrointestinal tract, and persistent abdominal
pain often complicates these lesions. (See "Diagnosis and management of chronic radiation
enteritis" and "Overview of gastrointestinal toxicity of radiation therapy" and "Chronic
intestinal pseudo-obstruction: Etiology, clinical manifestations, and diagnosis" and
"Gastroparesis: Etiology, clinical manifestations, and diagnosis".)
Lymphedema — Lymphedema may result from RT to the breast or shoulder, or to the

pelvis. The most common symptoms are heaviness, changes in skin, and discomfort or pain.
The disorder carries a high burden and recent advances present opportunities to improve
prevention and management [55]. Some patients with lymphedema develop stretch injuries
to the plexus or nerve entrapment syndromes, and as a result, experience neuropathic pain
[56]. The new onset of severe or progressive pain in a lymphedematous limb suggests tumor
recurrence infection, or a secondary malignancy (eg, Stewart-Treves syndrome) and requires
reevaluation. (See "Clinical features and diagnosis of peripheral lymphedema" and "Lower
extremity lymphedema" and "Breast cancer-associated lymphedema".)
Osteonecrosis — Radiation can cause osteoradionecrosis as a result of endarteritis

obliterans in the bone. Osteoradionecrosis of the jaw may follow RT for head and neck
cancers and is associated with pain and mechanical dysfunction. Osteonecrosis of other
bones occurs less often but may complicate RT at virtually any site. (See "Management of
late complications of head and neck cancer and its treatment", section on
'Osteoradionecrosis and soft tissue necrosis'.)
Medication-related osteonecrosis of the jaw can also occur as an uncommon but potentially
serious side effect in patients with metastatic bone disease who are treated with high-
potency bisphosphonates or denosumab to prevent skeletal-related events. (See
"Medication-related osteonecrosis of the jaw in patients with cancer".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Neuropathic pain"
and "Society guideline links: Cancer pain".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Managing pain when you have cancer (The
Basics)" and "Patient education: Mouth sores from cancer treatment (The Basics)")
SUMMARY
● A cancer pain syndrome is defined as a clinically meaningful constellation of symptoms

and signs in a patient with cancer. The identification of a specific pain syndrome in
cancer patients may help to elucidate the etiology, help direct the diagnostic evaluation,
clarify the prognosis for the pain or the disease itself, and guide subsequent
therapeutic interventions. (See 'Introduction' above.)
● Cancer pain syndromes may be broadly divided into those that are acute and those that
are chronic. Acute pain syndromes usually accompany diagnostic or therapeutic
interventions, although some are directly related to the malignancy itself (eg,
hemorrhage into a hepatocellular cancer, pathologic fracture, obstruction or
perforation of a bile duct, ureter, or bowel lumen). (See 'Acute pain syndromes' above.)
● Chronic pain syndromes are usually directly related to the neoplasm itself ( table 7) or
to an antineoplastic therapy (including chemotherapy, surgery, or radiation therapy
( table 8)). (See 'Chronic pain syndromes' above.)
Use of UpToDate is subject to the Terms of Use.
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Topic 2804 Version 46.0
GRAPHICS
Revised definition of pain
Pain
An unpleasant sensory and emotional experience associated with, or resembling that associated
with, actual or potential tissue damage.
Notes
Pain is always a personal experience that is influenced to varying degrees by biological,

psychological, and social factors.
Pain and nociception are different phenomena. Pain cannot be inferred solely from activity in
sensory neurons.
Through their life experiences, individuals learn the concept of pain.
A person's report of an experience as pain should be respected. [1]
Although pain usually serves an adaptive role, it may have adverse effects on function and social
and psychological well-being.
Verbal description is only one of several behaviors to express pain; inability to communicate does
not negate the possibility that a human or a nonhuman animal experiences pain.
Reference:
1. Declaration of Montréal. International Association for the Study of Pain. Available at: https://www.iasp-
pain.org/DeclarationofMontreal (Accessed on October 29, 2020).
From: Raja SN, Carr DB, Cohen M, et al. The revised International Association for the Study of Pain definition of pain: concepts,
challenges, and compromises. PAIN 2020; 161:1976. DOI: 10.1097/j.pain.0000000000001939. Copyright © 2020 International
Association for the Study of Pain. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this
material is prohibited.
Graphic 129909 Version 2.0
Acute pain syndromes associated with diagnostic and therapeutic

interventions
Acute pain syndromes associated with diagnostic interventions:
Lumbar puncture-associated and post-lumbar puncture headache
Arterial or venous blood sampling
Endoscopy and biopsy
Endometrial biopsy
Transrectal prostate biopsy
Percutaneous biopsy
Bone marrow biopsy
Acute pain syndromes associated with therapeutic interventions:

Pleurodesis/chest tube insertions
Percutaneous biliary stents
Abdominal paracentesis
Vascular embolization
Suprapubic catheterization
Nephrostomy tube insertion
Acute pain syndromes associated with analgesic techniques:

Injection-related pain
Opioid hyperalgesia syndrome
Epidural injection pain
Acute pain syndromes directly related to cancer
Acute pain syndromes directly related to cancer:
Rupture of hepatocellular carcinoma
Pathologic fractures from bone metastases (vertebral or long bones)
Acute intestinal/biliary/ureteric obstruction or perforation
Acute pain syndromes associated with infections:
Herpes zoster and postherpetic neuralgia
Acute pain syndromes associated with thrombotic events:
Deep vein thrombosis (upper and lower extremities)
Superior vena cava obstruction
Acute pain syndromes associated with antineoplastic treatments
Acute pain syndromes associated with chemotherapy infusion techniques:
Intravenous infusion pain (eg, oxaliplatin)
Venous spasm
Chemical phlebitis (vinorelbine, 5-fluorouracil)
Vesicant extravasation
Anthracycline-associated localized skin flare reaction at or adjacent to drug administration site
Hepatic artery infusion pain
Abdominal pain associated with intraperitoneal chemotherapy
Pain associated with intravesical instillation of chemotherapy
Acute pain syndromes associated with chemotherapy toxicity:

Oral mucositis
Painful peripheral neuropathy and plexopathy
Headaches (eg, due to intrathecal methotrexate meningitis syndrome, l-asparaginase-associated dural

sinus thrombosis, all trans-retinoic acid [ATRA]-related headache)
Arthralgias and myalgias
Palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome)
Post-chemotherapy acute limb ischemia
Fluoropyrimidine-induced angina
Post-chemotherapy gynecomastia
Steroid-induced perineal burning
ATRA-induced diffuse bone pain
Acute pain syndromes associated with hormonal therapy:

Tumor flare in advanced prostate cancer treated with luteinizing hormone releasing factor (LHRH)
agonists
Pain flare in metastatic breast cancer treated with estrogen receptor (ER) agonists such as tamoxifen or
high-dose estrogen
Acute pain syndromes associated with immunotherapy:

Interferon-associated myalgias
Acute pain syndromes associated with growth factors:

Bone pain induced by hematopoietic colony stimulating factors
Acute pain syndromes associated with radiotherapy:
Incident pain associated with positioning
Oropharyngeal mucositis
Early onset brachial plexopathy
Acute radiation enteritis or proctitis
Acute vertebral bone pain after radiation
Acute and subacute radiation myelopathy
Chemotherapy agents associated with mucositis
Category Specific Drugs
Alkylating agents Busulfan
Carboplatin
Cisplatin
Cyclophosphamide
Ifosfamide
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Anthracyclines Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone
6-Mercaptopurine
Antimetabolites
6-Thioguanine
Capecitabine
Cytarabine
Fludarabine
Fluorouracil
Gemcitabine
Hydroxyurea
Methotexate
Pemetrexed
Pralatrexate
Antitumor antibiotics Dactinomycin
Bleomycin
Mitomycin
Taxanes Docetaxel
Paclitaxel
Topoisomerase inhibitors Etoposide
Irinotecan
Teniposide
Topotecan
Cabozantinib
Molecularly targeted agents
Cetuximab
Erlotinib
Everolimus
Lenvatinib
Palbociclib
Panitumumab
Regorafenib
Sorafenib
Sunitinib
Temsirolimus
Acute pain syndromes associated with chemotherapy and/or hormonal

therapy
Syndrome Description
Chemotherapy-induced headaches Common after treatment with intrathecal methotrexate for

leukemia, lymphoma, or leptomeningeal carcinomatosis, all
trans retinoic acid (ATRA) for leukemia
May be associated with vomiting, nuchal rigidity, fever,

irritability, and lethargy
May last for several days or longer, and may or may not occur
with repeated administration
Arthralgia and myalgia Pain in joints or muscles
Reported by 20 percent of patients treated with paclitaxel
Palmar-plantar erythrodysesthesia Painful rash on the palms and soles following administration
(hand-foot syndrome) of specific chemotherapies (particularly liposomal doxorubicin
and capecitabine)
Rash may progress to bullous formation and desquamation
Postchemotherapy acute limb Reduced blood supply to the fingers and toes, described in
ischemia (Raynaud's phenomenon) survivors of testicular cancer, who were treated with
bleomycin, vinblastine, and cisplatin
Fluoropyrimidine-induced angina Fluorouracil (FU) and capecitabine increase risk of cardiac

ischemic episodes, presumably resulting from coronary
vasospasm
Postchemotherapy gynecomastia Prevalent when receiving chemotherapy for testicular cancer
Painful and usually transitory
Steroid-induced perineal burning Perineal burning: has been described immediately (within 30
seconds) after intravenous steroid infusion
Diffuse bone pain Known to occur with all trans-retinoic acid (ATRA)
Flare syndrome in advanced prostate Characterized by increased bone pain, at times associated
cancer, after initiation of LHRH agonist with added risk of cord compression, bladder outlet
alone obstruction and hypercoagulability
Can result from treatment with LHRH (lutenising hormone

releasing hormone) agonist therapy
Flare syndrome in advanced breast Characterized by diffuse musculoskeletal pain, skin erythema
cancer change in liver function studies and hypercalcemia
Can result from initial administration of tamoxifen or other

estrogen receptor agonists
Interferon-associated myalgias Pain in joints, possibly accompanied by fever and severe

fatigue, appearing shortly after initial diagnosis
Typically decreases in severity after repeated dosing
Chronic pain syndromes directly related to cancer
Nociceptive pain syndromes: Somatic
Tumor-related bone pain
Multifocal bone pain
Bone metastases
Bone marrow expansion (hematologic malignancies)
Oncogenic hypophosphatemic osteomalacia
Vertebral syndromes
Atlanto-axial destruction and odontoid fracture
C7-T1 syndrome
T12-L1 syndrome
Sacral syndrome
Back pain secondary to spinal cord compression
Pain syndromes related to pelvis and hip
Pelvic metastases
Hip joint syndrome
Malignant piriformis syndrome
Base of skull metastases
Orbital syndrome
Parasellar syndrome
Middle cranial fossa syndrome
Jugular foramen syndrome
Occipital condyle syndrome
Clivus syndrome
Sphenoid sinus syndrome
Tumor-related soft tissue pain
Headache and facial pain
Ear and eye pain syndromes
Pleural pain
Paraneoplastic pain syndromes
Muscle cramps
Hypertrophic osteoarthropathy
Tumor-related gynecomastia (eg, in testicular neoplasms that secrete human chorionic

gonadotropin)
Paraneoplastic pemphigus
Paraneoplastic Raynaud phenomenon
Nociceptive pain syndromes: Visceral

Hepatic distention syndrome
Midline retroperitoneal syndrome
Chronic intestinal obstruction
Peritoneal carcinomatosis
Malignant perineal pain
Adrenal pain syndrome
Ureteric obstruction
Neuropathic pain syndromes

Leptomeningeal metastases
Malignant painful radiculopathy
Painful cranial neuralgias
Glossopharyngeal neuralgia
Trigeminal neuralgia
Radiculopathies
Lumbosacral radiculopathy
Cervical radiculopathy
Thoracic radiculopathy
Plexopathies
Cervical plexopathy
Malignant brachial plexopathy
Malignant lumbosacral plexopathy
Lower lumbosacral plexopathies, including sacral and coccygeal plexopathy and panplexopathy
Painful peripheral mononeuropathies
Paraneoplastic sensory neuropathy
Chronic pain syndromes associated with cancer treatment
Chemotherapy-related pain syndromes
Bony complications of long-term corticosteroids
Avascular necrosis
Vertebral compression fractures
Carpal tunnel syndrome
Chemotherapy-induced peripheral neuropathy
Raynaud's syndrome
Hormonal therapy-related pain syndromes
Arthralgias
Dyspareunia
Gynecomastia
Myalgias
Osteoporotic compression fractures
Radiation-related pain syndromes
Chest wall syndrome
Cystitis
Enteritis and proctitis
Fistula formation
Lymphedema
Myelopathy
Osteoporosis
Osteoradionecrosis and fractures
Painful secondary malignancies
Peripheral mononeuropathies
Plexopathies: Brachial, sacral
Stem cell transplantation-mediated graft-versus-host disease
Arthralgias/myalgias
Dyspareunia, vaginal pain
Dysuria
Eye pain
Oral pain and reduced jaw motion
Paresthesias
Scleroderma-like skin changes
Surgical pain syndromes
Lymphedema
Postamputation phantom pain
Postmastectomy pain
Postradical neck dissection pain
Postsurgery pelvic floor pain
Postthoractomy pain/frozen shoulder
Postsurgery extremity pain (eg, sarcoma)
From: Paice JA, Portenoy R, Lacchetti C, et al. Management of Chronic Pain in Survivors of Adult Cancers: American Society of
Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34(27):3325-45. Reprinted with permission. Copyright © 2016
American Society of Clinical Oncology. All rights reserved.
Core diagnostic criteria for cancer-induced bone pain from the ACTTION-APS
collaboration
Criteria
1 History of primary or metastatic bone cancer diagnosed using imaging and physical examination
2 Presence of continuous, background pain (usually described as annoying, dull, gnawing, aching,
and/or nagging) in 1 or more locations generally consistent with known distribution of bone lesions
3 Presence of evoked or spontaneous pain (often described as electric or shock-like) in 1 or more

locations generally consistent with known distribution of bone lesions, associated with weight
bearing or movement or can occur spontaneously
4 Clinical examination over the site of pain reveals:

Hyperalgesia to blunt, non-noxious pressure or pin-prick stimuli
Hypoesthesia to non-noxious thermal stimuli
Hypoesthesia to light touch stimuli
ACTTION: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities,
and Networks; APS: American Pain Society.
Reproduced from: Paice JA, Mulvey M, Bennett M, et al. AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions. J Pain
2017; 18:233. Table used with the permission of Elsevier Inc. All rights reserved.
Tumor-related vertebral pain syndromes in cancer patients
Syndrome Characteristics
Atlantoaxial destruction and Nuchal or occipital pain that often radiates over the posterior aspec
odontoid fracture of the skull
Patients usually present with insidious neurological deficits in one

or more extremities
C7-T1 syndrome Pain in the interscapular region caused by tumor invasion of a C7 or

T1 vertebra
T12-L1 syndrome Referred pain at the ipsilateral crest or sacroiliac joint caused by
tumor invasion of a T12 or L1 vertebra
Sacral syndrome Pain radiating to buttocks, perineum, or posterior thighs
Intense pain with hip adduction and internal rotation due to

stretching of pyriformis muscle
Spinal nerves section through thoracic vertebra
Tumor-related base of skull syndromes in cancer patients
Orbital syndrome Increasing pain in the retroorbital and supraorbital regions of the affected eye
Associated problems include blurred vision, diplopia, proptosis, chemosis

(conjunctival edema), external ophthalmoplegia, ipsilateral papilledema, and
decreased sensation in the ophthalmic division of the trigeminal nerve
Parasellar syndrome Neoplastic invasion in the parasellar region can lead to unilateral supraorbital
and frontal headache, as well as diplopia
Middle cranial fossa Pain and sensory changes in the distribution of the mandibular and maxillary
syndrome divisions of the trigeminal nerve. May be associated with headache, diplopia,
dysarthria, dysphagia, facial numbness, paresthesias, or pain referred to the
cheek or jaw.
Jugular foramen and Afffects the glossopharyngeal, vagus, and accessory nerves. Throat pain,
hypoglossal hoarseness, dysphasia, deep aching in the ipsilateral mastoid region, and
syndrome glossopharyngeal neuralgia with or without bradycardia and syncope.
Neurological signs may include Horner's syndrome and weakness of the palata
muscles, sternocleidomastoid, or trapezius muscles
Occipital condyle Presents with severe unilateral occipital pain that is worsened by neck flexion,
syndrome neck stiffness
Almost always includes concomitant involvement of hypoglossal canal leading

to paresis and atrophy of ipsilateral tongue
Physical examination may reveal head tilt, limited movement of neck,

tenderness to palpation over occipito-nuchal junction
Clivus syndrome Severe headache maximally experienced at vertex and worse with neck flexion,
sixth nerve palsy
Sphenoid sinus Bifrontal headache radiating to the temples and retroorbital areas
syndrome
May present with associated nasal congestion and diplopia from sixth nerve
palsy
Fracture of the Posterior headache, worse on neck flexion. Instability of the cervical spine or
odontoid process mass effect from tumor may cause spinal cord or brainstem compression.
(dens)
Plexopathies in cancer patients
Syndrome Description
Cervical Aching and burning pain in periauricular or postauricular area, or anterior neck
plexopathy
Pain may be referred to the lateral aspect of the face, head, or shoulder
Brachial Moderate to severe pain with component that is dysesthetic and described as
plexopathy burning or freezing
Allodynia may accompany pain
Lumbosacral Presents as pain, followed by numbness, paresthesias, or weakness

plexopathies
Other symptoms include focal tenderness, leg edema, and positive direct or reverse
straight leg raising signs
Distribution of pain is related to the location of the neoplasm:
- Upper lumbosacral plexopathy (L1-4): Pain experienced in the anterolateral thigh,

knee, and proximal leg/lower abdomen; generally caused by low abdominal tumors;
upper lumbosacral plexopathy associated with malignant involvement of the psoas
major muscle is termed "malignant psoas syndrome"
- Lower lumbosacral plexopathy (L4-S1): Pain may be focal in buttocks and perineum
and referred to posterolateral thigh and leg; weakness or sensory changes in L5 and
S1 dermatomes; leg edema, bladder dysfunction, or bowel dysfunction; generally
caused by sigmoid or rectal tumors
- Sacral plexopathy (S1-3): May lead to dysesthesias in buttocks, perineum, or

posterior legs; pain often severe while sitting, less severe while standing, and least
severe while walking; numbness over the dorsolateral foot and weak ankle
dorsiflexion; mostly associated with low midline tumors (eg, rectal cancer)
- Panplexopathy: Pain anywhere from lower abdomen, back, buttocks, or perineum;

referred pain experienced anywhere in the distribution of the plexus
- Coccygeal plexopathy (S4-coccygeal nerve): May present as anal pain, numbness,

and sphincter dysfunction; most common with rectal and prostate tumors
Trunks and cords of the brachial plexus
Core diagnostic criteria for pancreatic cancer pain from the ACTTION-APS
collaboration
Criteria
1 History of pancreatic cancer diagnosed using imaging, physical examination, and in some cases,
biopsy and laboratory analysis of blood or tissues for tumor markers
2 Presence of pain in the upper abdominal region (typically referred to the epigastric region or upper
abdominal quadrants) spreading posteriorly and/or radiating to the back
3 On clinical examination, the patient displays tenderness on upper abdominal palpation
4 No other condition (eg, constipation) could plausibly account for persisting pain in the upper
abdomen
ACTTION: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities,
and Networks; APS: American Pain Society.
Reproduced from: Paice JA, Mulvey M, Bennett M, et al. AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions. J Pain
2017; 18:233. Table used with the permission of Elsevier Inc. All rights reserved.
Pain from paraneoplastic syndromes in cancer patients
Chronic sensorimotor Mild to moderate distal symmetric sensorimotor defects with symmetric
neuropathy pain that begins in the feet and gradually ascends
Hypertrophic Clubbing of fingers, periostitis of long bones, and occasionally a

osteoarthropathy rheumatoid-like polyarthritis
Pain, tenderness, and swelling in the knees, wrists, and ankles
Paraneoplastic Breast enlargement, usually presenting with pain

gynecomastia
Paraneoplastic pemphigus Widespread mucocutaneous lesions involving the lips, conjunctiva, and
genitalia
When severe, desquamation can occur and death may occur from fluid
loss, infection, or an associated bronchiolitis obliterans
Paraneoplastic Raynaud's Intense vasospasm of digital arterioles leading to pallor, followed by

phenomenon cyanosis and subsequent hyperemia of the fingertips
Subacute sensory "Pins and needles" or electric-shock sensations initially affecting an

neuronopathy extremity and progresses to involve other extremities, the face, abdomen
and trunk
Clubbing of the fingers
In a normal finger, the length of the perpendicular dropped from point A to point B should be greater
than a similar line from C to D. In clubbing, the relationships are reversed; that is, the distance C-D is
greater than the distance A-B. The other important change is the angle described by A-C-E. In the
normal finger, this is usually <180°, whereas in clubbing, it is >180°.
Panels A and C redrawn from: DeRemee RA. Facets of the algorithmic synthesis. In: DeRemee RA, (Ed), Clinical profiles of
diffuse interstitial pulmonary disease, Mount Kisco, NY, Futura Publishing Company, Inc, 1990, pp. 9-44.
Panel B redrawn from: Bates B. A Guide to Physical Examination and History Taking, 5th Ed. Philadelphia: J.B. Lippincott
Company, 1991.
Pulmonary osteoarthropathy
This plain film of the hand in a 41-year-old female who presented with severe hand and ankle pain
demonstrates marked periosteal new bone formation adjacent to the first metacarpal bone (arrows).
A chest radiograph revealed a large solitary mass subsequently shown to represent an
adenocarcinoma.
Courtesy of Jonathan Kruskal, MD, PhD.
Pulmonary osteoarthropathy
This plain film of the lower extremity in a female who presented with ankle pain demonstrates
marked periostitis with cortical and periosteal thickening, which has arisen in this patient with
adenocarcinoma of the lung.
Courtesy of Jonathan Kruskal, MD, PhD.
Core diagnostic criteria for chronic pain related to chemotherapy-induced

peripheral neuropathy
Criteria
1 Onset of pain after exposure to chemotherapeutic agent known to be neurotoxic
2 Presence of painful symptoms in a symmetrical stocking and glove distribution beginning in lower
extremities, which may progress to the upper extremities, although finding in the feet and not in
the hands is common
3 Painful symptoms are accompanied by nonpainful symptoms (eg, "pins and needles" or numbness)
in a similar distribution
4 Clinical examination reveals sensory loss to 1 or more sensory modalities and/or evoked pain in a
stocking and glove distribution, as reflected in at least 1 of the following:
Bilateral increase in detection thresholds to tactile, vibration, or non-noxious warm or cool
stimuli
Bilateral increase in pain detection thresholds to blunt pressure or pinprick stimuli
Bilateral decrease in pain detection threshold to noxious heat or cold stimuli
5 Magnitude of the sensory abnormalities is disproportionately greater than the magnitude of any
motor abnormalities in the affected region (except in the case of neuropathy after vinca alkaloids)
6 No other condition (eg, polyneuropathy of other origin) could plausibly account for painful
symptoms
Original figure modified for this publication. From: Paice JA, Mulvey M, Bennett M, et al. AAPT Diagnostic Criteria for Chronic
Cancer Pain Conditions. J Pain 2017; 18:233. Table used with the permission of Elsevier Inc. All rights reserved.
Chronic post-surgical pain syndromes in cancer patients
Post-mastectomy Dull, burning, and aching pain experienced over the axilla, anterior chest wall
pain syndrome and medial upper arm, associated with sensory loss and sometimes phantom
sensations
May be accompanied by dysesthesia, allodynia, and scar sensitivity
Pain can start acutely post-surgery and persist, or onset may occur many
months or years after surgery
Post-radical neck Often neuropathic and described as a burning or lancinating dysesthesias in

dissection pain the anterolateral neck extending to the shoulder; reflects injury to the cervical
plexus
Often accompanied by sensory loss
May experience neck and shoulder pain weeks to months after surgery
Post-thoracotomy Neuropathic pain localized to the region of the thoracotomy scar, experienced
pain months post-surgery; when recurrent rather than persistent, high suspicion for
tumor regrowth
Pain described as aching or burning; potentially associated with sensory and

autonomic changes; may be accompanied by ipsilateral arm disability
Postoperative frozen Limited shoulder range of motion usually caused by untreated thoracotomy
shoulder pain and inadequate rehabilitation
Post-surgery pelvic Resembles the idiopathic syndrome of tension myalgia of the pelvic floor, with
floor pain pain that occurs on standing
Stump pain Neuropathic pain, described as burning, experienced at the site of a surgical
scar several months to years post-amputation
Pain may be exacerbated by movement and is secondary to neuroma

formation in the region of amputation
May be improved or exacerbated by wearing of a prosthesis
Phantom limb pain Site of pain is away from amputation scar and appears to be where the absent
limb was located
Pain is dysesthetic, often fluctuating
May or may not be associated with phantom sensations, including nonspecific

paresthesia and specific sensations of the limb, with or without distortions
Phantom pain Phantom breast pain following mastectomy
Phantom pelvic pain following hemipelvectomy
Phantom rectal pain following rectal cancer surgery
Phantom eye pain in patients with eye enucleation

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27/2/24, 22:00 Overview of cancer pain syndromes - UpToDate

Official reprint from UpToDate®

Literature review current through: Jan 2024.

ACUTE PAIN SYNDROMES

● "Breakthrough pain" is typically defined as a transient flare of moderate to severe pain

● Pathologic fracture – A pathologic fracture is a bone fracture that occurs within a

● Obstruction/perforation of a hollow viscus – Obstruction of a bile duct, ureter, or

Although newer RT approaches such as three-dimensional conformal RT (3D-CRT) and

A year 2020 evidence-based review by the Multinational Association of Supportive Care in

Chemotherapy-induced neuropathy — Many chemotherapeutic agents are neurotoxic.

Chemotherapy-induced neuropathic pain usually gradually improves after the treatment is

Rare overall, acute chemotherapy-related mononeuropathy is best described with vincristine.

Other chemotherapy-related acute pain syndromes — Specific chemotherapeutic agents

Intrathecal therapy for leptomeningeal metastatic disease, intraperitoneal therapy for

Radiation therapy-induced bone pain — Approximately one-third of patients undergoing

Radiation enteritis and proctitis — Patients undergoing abdominal irradiation may

CHRONIC PAIN SYNDROMES

A significant barrier to better understanding chronic cancer pain syndromes, their

Tumor-related somatic pain syndromes — Tumor involvement of bone, joints, muscle, or

In addition, a rare paraneoplastic form of renal phosphate wasting called oncogenic

Neoplastic epidural spinal cord compression (ESCC) is a common complication of solid

provided. Surgical decompression is considered if the tumor type is typically

Treatment of cancer-associated muscle cramps is nonspecific and employs the same

Tumor-related visceral pain syndromes — Visceral pain can be caused by obstruction of

● Hepatic distention syndrome – Pain-sensitive structures in the region of the liver

● Midline retroperitoneal syndrome – Tumor invasion of the pancreas or other

● Chronic intestinal obstruction – Diffuse abdominal pain may be related to chronic

Pain may be continuous or colicky, and may be referred to the dermatomes

● Peritoneal carcinomatosis – Carcinomatous seeding of the peritoneum leads to

● Malignant perineal pain – Malignancy-related perineal pain is most often associated

● Ureteral obstruction – Gastrointestinal, genitourinary and gynecologic cancers are the

Leptomeningeal metastases — Any solid or hematologic neoplasm can potentially

Clinical presentation is variable:

● These variable pains may be accompanied by an equally diverse set of neurologic

The diagnosis of a leptomeningeal neoplasm is made by the finding of malignant cells on

Cranial neuralgias — Malignancy-related cranial neuralgias can develop from metastases

● Glossopharyngeal neuralgia – Glossopharyngeal neuralgia is characterized by

● Trigeminal neuralgia – A syndrome that mimics idiopathic trigeminal neuralgia may

Radiculopathies — Any malignant process that compresses, distorts, or inflames nerve

Radicular pain may be continuous or intermittent, aching or sharp, or dysesthetic (eg,

A high index of suspicion for a malignant cause of radiculopathy or polyradiculopathy should

Plexopathies — Tumor-related plexopathies may involve the cervical, brachial, or

If there is involvement of the superior cervical (stellate) ganglion of the sympathetic

The usual cause of a malignant brachial plexopathy is local extension of a primary or

The pain is classically followed by paresthesias in the distribution innervated by the

The diagnosis of neoplastic versus radiation-induced brachial plexopathy is suggested

The diagnosis of a radiation-induced rather than neoplastic plexopathy is supported by

● Lumbosacral plexopathy – Malignant lumbosacral plexopathy is primarily associated

The diagnostic evaluation of a patient with a lumbosacral plexopathy is described in

Peripheral mononeuropathies — Painful peripheral mononeuropathies can result from

Paraneoplastic syndromes — Paraneoplastic syndromes are a heterogeneous group of

antibodies or other compounds produced through immune responses. Paraneoplastic

● Subacute sensory neuronopathy – One of the best characterized painful neurologic

Other, more prevalent paraneoplastic polyneuropathies comprise axonopathies that

● Hypertrophic osteoarthropathy – Hypertrophic osteoarthropathy is a syndrome

Headache — A new, changed, or progressive headache in a patient with a history of cancer

Chronic pain related to antineoplastic treatments — Chemotherapy (including

Chemotherapy-related neuropathy — Although painful peripheral neuropathy resulting

Bone complications and glucocorticoids — Chronic use of glucocorticoids may cause

Steroids also accelerate osteoporosis, which may predispose to vertebral compression

Antiandrogens and gynecomastia — Painful gynecomastia develops in the majority of