Background
Cancer pain is a result of cancer growth in human tissues or the pain produced by any of the therapies implemented to treat it. Ideal management starts with a thorough assessment via the history and physical examination, as well as the judicious use of diagnostic testing in an attempt to define the pathophysiologic components involved in the expression of pain to implement optimal analgesic therapy. Adequate pain control can be achieved in the great majority of patients with the implementation of aggressive pharmacologic treatment consisting of the use of opioids and adjuvants. With the implementation of these strategies, 90% to 95% of patients may achieve adequate pain control. Consequently, 5% to 10% of patients will need some form of invasive therapy. Thus, when following specific guidelines, the great majority of patients with cancer-related pain may expect adequate pain control in the 21st century. Control of pain and related symptoms is a cornerstone of cancer treatment in that it promotes an enhanced quality of life, improved functioning, better compliance, and a means for patients to focus on matters that give meaning to life. In addition to their salutary effects on quality of life, mounting evidence suggests that good pain control influences survival.
Epidemiology
Approximately 6.35 million new cases of cancer are diagnosed annually worldwide, half of which originate in developing nations and 1.04 million occur in the United States alone. Mortality is high; one in five deaths in the United States is a result of cancer, which means about 1400 cancer-related deaths per day. The morbidity is equally concerning inasmuch as up to 50% of patients undergoing treatment of cancer and up to 90% of patients with advanced cancer have pain. Most (65%) cancer pain is due to involvement of organic structures by tumor, notably bone, neural tissue, viscera, and others. Up to 25% of cancer pain is due to therapy, including chemotherapy, radiotherapy, and surgery, and the rest of “cancer pain” is accounted for by common chronic pain syndromes, including back pain and headaches, which might have been exacerbated by the ongoing growth or treatment of cancer. As new therapeutic regimens are introduced for the treatment of cancer, it is expected that cancer patients will be living longer and potentially experiencing pain as a result of cancer disease itself or therapies implemented for its control for longer periods.
Anorexia, fatigue, and pain are the most common symptom associated with cancer. Significant pain is present in up to 25% of patients undergoing active treatment and in up to 90% of patients with advanced cancer. According to several studies, including a survey of oncologists in the Eastern Cooperative Oncology Group (ECOG) and a survey of 1103 consecutive admissions to a U.S tertiary care cancer hospital, 73% of patients in active treatment admitted to having pain, with 38% reporting severe pain. Despite the availability of simple, cost-effective treatments, inadequately controlled pain remains a significant problem. This is important because of the negative influence of pain on patients’ performance status.
Performance status, as measured by the ECOG and Karnofsky scales ( Table 23.1 ), is a global rating of patients’ overall functional status. When performance status is low, as is often the case when pain is severe, patients may find it difficult to tolerate the chemotherapy recommended; indeed, they may not be considered candidates for chemotherapy. Further benefits of good pain management often include improvement in nutrition, rest, and mood, all of which contribute to quality of life and have the potential to influence the outcome of antineoplastic therapy.
| ECOG Scale ∗ | Karnofsky Scale † | ||
|---|---|---|---|
| 0 | Fully active, able to carry out all predisease performance without restriction | 100 | Normal; no complaints, no evidence of disease |
| 1 | Restricted in physically strenuous activity but ambulatory and able to carry out light or sedentary work (e.g., light housework, office work) | 90 | Able to carry out normal activity; minor signs or symptoms of disease |
| 2 | Ambulatory and capable of all self-care but unable to work; up and about more then 50% of waking hours | 80 | Normal activity with effort; some signs or symptoms of disease |
| 3 | Capable of only limited self-care, confined to bed or chair more than 50% of waking hours | 70 | Cares for self; unable to carry out normal activity or to do active work |
| 4 | Completely disabled, cannot carry on any self-care. Totally confined to bed or chair | 60 | Requires occasional assistance but is able to care for most needs |
| 5 | Dead | 50 | Requires considerable assistance and frequent medical care |
| 40 | Disabled, requires special care and assistance | ||
| 30 | Severely disabled, hospitalization indicated; death not imminent | ||
| 20 | Very sick, hospitalization necessary; active supportive treatment necessary | ||
| 10 | Moribund; fatal processes; progressing rapidly | ||
| 0 | Dead | ||
∗ Oken MM, Creech RH, Tormey DC, et al, Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol . 1982;5:649-655.
† Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol . 1984;2:187-193.
Epidemiology
Approximately 6.35 million new cases of cancer are diagnosed annually worldwide, half of which originate in developing nations and 1.04 million occur in the United States alone. Mortality is high; one in five deaths in the United States is a result of cancer, which means about 1400 cancer-related deaths per day. The morbidity is equally concerning inasmuch as up to 50% of patients undergoing treatment of cancer and up to 90% of patients with advanced cancer have pain. Most (65%) cancer pain is due to involvement of organic structures by tumor, notably bone, neural tissue, viscera, and others. Up to 25% of cancer pain is due to therapy, including chemotherapy, radiotherapy, and surgery, and the rest of “cancer pain” is accounted for by common chronic pain syndromes, including back pain and headaches, which might have been exacerbated by the ongoing growth or treatment of cancer. As new therapeutic regimens are introduced for the treatment of cancer, it is expected that cancer patients will be living longer and potentially experiencing pain as a result of cancer disease itself or therapies implemented for its control for longer periods.
Anorexia, fatigue, and pain are the most common symptom associated with cancer. Significant pain is present in up to 25% of patients undergoing active treatment and in up to 90% of patients with advanced cancer. According to several studies, including a survey of oncologists in the Eastern Cooperative Oncology Group (ECOG) and a survey of 1103 consecutive admissions to a U.S tertiary care cancer hospital, 73% of patients in active treatment admitted to having pain, with 38% reporting severe pain. Despite the availability of simple, cost-effective treatments, inadequately controlled pain remains a significant problem. This is important because of the negative influence of pain on patients’ performance status.
Performance status, as measured by the ECOG and Karnofsky scales ( Table 23.1 ), is a global rating of patients’ overall functional status. When performance status is low, as is often the case when pain is severe, patients may find it difficult to tolerate the chemotherapy recommended; indeed, they may not be considered candidates for chemotherapy. Further benefits of good pain management often include improvement in nutrition, rest, and mood, all of which contribute to quality of life and have the potential to influence the outcome of antineoplastic therapy.
| ECOG Scale ∗ | Karnofsky Scale † | ||
|---|---|---|---|
| 0 | Fully active, able to carry out all predisease performance without restriction | 100 | Normal; no complaints, no evidence of disease |
| 1 | Restricted in physically strenuous activity but ambulatory and able to carry out light or sedentary work (e.g., light housework, office work) | 90 | Able to carry out normal activity; minor signs or symptoms of disease |
| 2 | Ambulatory and capable of all self-care but unable to work; up and about more then 50% of waking hours | 80 | Normal activity with effort; some signs or symptoms of disease |
| 3 | Capable of only limited self-care, confined to bed or chair more than 50% of waking hours | 70 | Cares for self; unable to carry out normal activity or to do active work |
| 4 | Completely disabled, cannot carry on any self-care. Totally confined to bed or chair | 60 | Requires occasional assistance but is able to care for most needs |
| 5 | Dead | 50 | Requires considerable assistance and frequent medical care |
| 40 | Disabled, requires special care and assistance | ||
| 30 | Severely disabled, hospitalization indicated; death not imminent | ||
| 20 | Very sick, hospitalization necessary; active supportive treatment necessary | ||
| 10 | Moribund; fatal processes; progressing rapidly | ||
| 0 | Dead | ||
∗ Oken MM, Creech RH, Tormey DC, et al, Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol . 1982;5:649-655.
† Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol . 1984;2:187-193.
Assessment of Pain Intensity
Questionnaires have been used to aid in standardizing patients’ assessment. Ideally, this assessment is completed by patients before their evaluation. The Wisconsin Brief Pain Inventory (BPI) and the Memorial Pain Assessment Card are becoming increasingly well accepted. The characteristics of the different assessment tools are noted in the following outline:
- 1.
Wisconsin BPI :
- a.
It is a fifteen-minute questionnaire that can be self-administered.
- b.
It includes several questions about the characteristics of the pain, including its origin and the effects of previous treatments.
- c.
It incorporates two valuable features of the McGill Pain Questionnaire, a graphic representation of the location of the pain and groups of qualitative descriptors. Severity of pain is assessed by a series of visual analog scale (VAS) scores that quantify pain at its best, worst, and on average. The perceived level of interference with normal function is quantified with a VAS also.
- d.
Preliminary evidence suggests that the BPI is cross-culturally applicable and is useful, particularly when patients are not fit to complete a more thorough or comprehensive questionnaire.
- a.
- 2.
Memorial Pain Assessment Card :
- a.
It is a simple, efficient, and valid instrument that provides rapid clinical evaluation of the major aspects of pain experienced by cancer patients.
- b.
It is easy to understand and use and can be completed by experienced patients in 20 seconds.
- c.
It consists of a two-sided, 8.5- × 11-inch card that is folded so that four separate measures are created.
- d.
It features scales intended for measurement of pain intensity, pain relief, and mood and a set of descriptive adjectives.
- a.
- 3.
Edmonton staging system :
- a.
It is performed by health care providers.
- b.
It was developed to predict the likelihood of achieving effective relief of pain in cancer patients.
- c.
The system’s originators provided validation that treatment outcome can be accurately predicted according to five clinical features (neuropathic pain, movement-related pain, recent history of tolerance to opioids, psychological distress, and a history of alcoholism or drug abuse).
- d.
Staging requires only 5 to 10 minutes and no special skills are needed to complete it.
- e.
Its value lies in prospective identification of potentially problematic patients, thereby further legitimizing clinical research on control of symptoms by introducing better standardization and improving our ability to critically assess the results of various therapeutic interventions in large population of patients.
- a.
- 4.
Pediatric cancer pain assessment : This includes Beyer’s The Oucher, Eland’s color scale–body outline, Hester’s poker chip tool, McGrath’s faces scale, and others.
- 5.
Numerical rating scale (NRS) or VAS :
- a.
Pain is often assessed on an 11-point NRS from 0 (no pain) to 10 (worst pain imaginable).
- b.
The VAS is a 10-cm line without markings from no pain to worst pain; patients mark their pain score and a measurement in centimeters defines their level of pain.
- a.
Evaluation of pain should be integrated with a detailed oncologic, medical, and psychosocial assessment. The initial evaluation should include an evaluation of the patient’s feelings and attitudes about the pain and disease, family concerns, and the patient’s premorbid psychological history. A comprehensive but objective approach to assessment instills confidence in patients and family that will be valuable throughout treatment. A comprehensive evaluation of patients with cancer pain includes the following:
- •
The reason for the visit is determined to ensure appropriate triage (e.g., patients with severe pain because of bowel obstruction may need to be sent to the emergency center for urgent treatment).
- •
An oncologic history is obtained to gain knowledge of the context of the pain problem and includes diagnosis and stage of the disease; a history of therapies implemented, including a list of the chemotherapeutic agents used, types of surgery, site of radiotherapy, and outcome (including side effects); and the patient’s understanding of the disease process and prognosis.
- •
The pain history should include any premorbid chronic pain and, for each new pain site, its onset and evolution, site and radiation areas, pattern (constant, intermittent, or unpredictable), intensity (best, worst, average, current) on VAS scales, quality, exacerbating and relieving factors, interference of the pain with usual activities, neurologic and motor abnormalities (including bowel and bladder continence), vasomotor changes, and current and past analgesics (use, efficacy, side effects). Previous analgesic use, efficacy, and side effects should be cataloged. Prior treatments of pain should be noted (radiotherapy, nerve blocks, physiotherapy, etc.).
- •
The medical record and radiologic studies should be reviewed. Many of the treatments of cancer may cause pain themselves (chemotherapy- and radiotherapy-induced neuropathy or postoperative pain syndromes such as post-thoracotomy and post-mastectomy pain syndrome), and many specific cancers may cause well-established pain patterns as a result of known probable sites of metastasis, including (1) metastasis of breast cancer to long bones, the spine, chest wall, brachial plexus, and spinal cord; (2) metastasis of colon cancer to the pelvis, hips, lumbar plexus, sacral plexus, and spinal cord; and (3) metastasis of prostate cancer to long bones, the pelvis, hips, lung, and spinal cord.
- •
The psychosocial history should include marital and residential status, employment history and status, educational background, functional status, activities of daily living, recreational activities, support systems, health and capabilities of the spouse or significant other, and past history of (or current) drug or alcohol abuse.
- •
The medical history (independent of the oncologic history) should include coexisting systemic disease, exercise intolerance, allergies to medications, medications in use, previous illness and surgery, and a thorough review of systems, including the following:
- •
General (anorexia, weight loss, cachexia, fatigue, weakness, insomnia)
- •
Neurologic (sedation, confusion, hallucination, headache, motor weakness, altered sensation, incontinence)
- •
Respiratory (dyspnea, cough, pneumonia)
- •
Gastrointestinal (dysphagia, nausea, vomiting, dehydration, constipation, diarrhea)
- •
Psychological (irritability, anxiety, depression, dementia)
- •
Genitourinary (urgency, hesitancy, hematuria)
- •
- •
The physical examination must be thorough, although at times it is appropriate to perform a focused examination of particular problems. In patients with spinal pain and known or suspected metastatic disease, a complete neurologic examination is mandatory.
- •
A care team meeting should be arranged if applicable.
- •
The need for further studies should be determined.
- •
Formulate a clinical impression ( diagnosis ). Multiple diagnoses usually apply, and it is optimal to use the most specific known diagnosis, such as somatic pain from a vertebral metastasis, severe pain in a patient with metastatic non–small cell carcinoma of the lung, and neuropathic pain from a paravertebral mass invading the nerve root as it exits the vertebral foramen. Nausea and vomiting with severe weight loss and fatigue, as well as constipation, should be identified.
- •
Formulate recommendations ( plan ) and alternatives for each problem. For instance, with respect to the examples just presented in formulating a clinical impression, one could perform magnetic resonance imaging (MRI) of the spine, add a controlled-release opioid administered daily and transmucosal fentanyl citrate for breakthrough pain, implement therapy with a combination of a tricyclic antidepressant and an anticonvulsant with instructions on titration, prescribe an antiemetic before meals and as needed for nausea, prescribe a bowel stimulant and bulk-forming compound twice daily for constipation, and evaluate in 2 weeks to determine the need for a short course of steroid therapy.
- •
Call an oncologist or the primary care provider , or both, if applicable. Have a discussion with the referring physician, primary care provider, and/or oncologist to establish short- and long-term plans.
- •
Conduct an exit interview.
- •
Explain the probable cause of the symptoms in terms that the patient can understand.
- •
Discuss the prognosis for relief of symptoms, management options, and specific recommendations. In addition to writing prescriptions, oral and written instructions must be provided. Educational material regarding medications, pain management strategies, or procedures should also be provided. Potential side effects and their management should be discussed.
- •
Arrange for follow-up with clinic contact information.
- •
Dictate a summary of the evaluation to the referring and consulting physicians.
- •
Classification of Cancer Pain
Time Related
Acute Pain
Acute pain is frequently associated with sympathetic hyperactivity and heightened distress. It is often temporally associated with the onset or recrudescence of primary or metastatic disease, and its presence should motivate the clinician to aggressively seek its cause and adjust the pharmacologic therapeutic scheme.
Subacute Pain
Some patients experience subacute pain for 4 to 6 weeks after a major surgical procedure. This type of pain is largely undertreated and deserves special attention because it may affect the patient’s ability to perform activities of daily living after discharge from the hospital.
Chronic Pain
Treatment of pain of a chronic nature mandates a combination of palliation, adjustment, and acceptance. With time, biologic and behavioral adjustment to the symptoms occurs, and hopefully the associated symptoms will be blunted. Chronic pain with superimposed episodes of acute pain (breakthrough pain) is probably the most common pattern observed in patients with ongoing cancer pain.
Intensity
Consistent use of measurements of pain intensity aids in monitoring a patient’s progress and may serve as a basis for interpatient comparisons. High pain scores may alert the clinician to the need for more aggressive treatment or hospitalization (or both) for rapid control of symptoms via intravenous patient-controlled analgesia (IV PCA) or for antineuropathic medications with a rapid titration protocol.
Pathophysiology
A mechanistic approach is useful when formulating the initial treatment plan, as suggested in the example above.
Somatic pain is described as a constant, well-localized pain often characterized as aching, throbbing, sharp, or gnawing. It tends to be responsive to opioids and nonsteroidal anti-inflammatory drugs (NSAIDs—cyclooxygenase-2 inhibitors) and amenable to relief by interruption of proximal pathways via neural blockade when indicated.
Visceral pain originates from injury to organs. This pain is transmitted by fibers that travel along the sympathetic nervous system. Visceral pain is characteristically vague in distribution and quality and is often described as a deep, dull, aching, dragging, squeezing, or pressure-like sensation. When acute, it may be paroxysmal and colicky and can be associated with nausea, vomiting, diaphoresis, and alterations in blood pressure and heart rate. Mechanisms of visceral pain include abnormal distention or contraction of smooth muscle walls (hollow viscera), rapid capsular stretch (solid viscera), ischemia of visceral muscle, serosal or mucosal irritation by algesic substances and other chemical stimuli, distention and traction or torsion on mesenteric attachments and the vasculature, and necrosis. The viscera, however, are insensitive to simple manipulation, cutting, and burning. Visceral involvement often produces referred pain (e.g., shoulder pain of hepatic origin).
Neuropathic pain is defined as pain caused by injury or irritation to some element or elements of the nervous system. Examples of neuropathic pain syndromes include tumor growth around nerve structures; postsurgical pain syndromes such as post-thoracotomy, post-mastectomy, post–radical neck dissection, and post-hepatectomy pain; or pain induced by chemotherapeutic agents affecting peripheral nerve structures. Chemotherapeutic agents associated with this problem include vinca alkaloids (vincristine, vinblastine), cisplatin, paclitaxel (Taxol), docetaxel (Taxotere), vinorelbine (Navelbine), and bortezomib (Velcade). Neuropathic pain is often resistant to standard analgesic therapies and frequently requires an approach using combinations of opioids, tricyclic antidepressants, anticonvulsants, oral or topical local anesthetics, corticosteroids, N -methyl- d -aspartate (NMDA) blockers, and others.
Temporal Aspects of Pain
Constant Pain
Such pain is most amenable to drug therapy administered around the clock, contingent on time rather than symptoms. It is best managed by long-acting analgesics or, in selected cases, infusion of analgesics.
Breakthrough Pain and Incident Pain
Breakthrough pain that is related to a specific activity, such as eating, defecation, socializing, or walking, is referred to as incident pain. Incident pain is best managed by supplementing the preventive around-the-clock regimen with analgesics that have a rapid onset of action and a short duration. Once a pattern of incident pain is established, escape or rescue doses of analgesics can be administered in anticipation of the pain-provoking activity. Breakthrough pain that occurs consistently before the next scheduled dose of around-the-clock opioids is called end-of-dose failure (plasma concentrations fall below minimum effective analgesic concentrations) and is ideally managed by reducing the intervals between doses. In contrast, increasing the doses of long-acting opioids under these circumstances may increase the incidence of side effects. Under a strict definition, breakthrough pain is pain that may occur at any time during the day; it increases to a high intensity very rapidly and has duration of 30 to 45 minutes. Consequently, it is important to recognize the differences among these three types of breakthrough pain to implement adequate therapy.
Intermittent Pain
This type of pain is very unpredictable and can best be managed by the administration of potent analgesics with a rapid onset and short duration as needed.
Specific Cancer Pain Syndromes
Metastases
Bone tumor infiltration or bone metastasis is cited as the most common cause of cancer pain and is most often seen with stage IV carcinoma of the prostate, breast, thyroid, lung, or kidney. The pain is usually constant, dull, achy or deep, and often intense with movement or weight bearing. Approximately 25% of patients with bone metastases experience pain. Pressure and chemical irritation of nerve endings in the periosteum may cause pain. It is noteworthy that greater than 50% decalcification must occur before osseous lesions are visible on plain radiographs. Thus, a bone scan (isotope scanning, scintigraphy) is preferred for detecting most bone metastases. Nonetheless, with primary bone tumors, thyroid cancer, and multiple myeloma, plain films are considered to be more sensitive. Neoplastic changes must be differentiated from changes related to infection, trauma, or degeneration because treatment differs, even in patients with cancer.
Prostaglandin E 2 (PGE 2 ) and other cytokines are elaborated by osseous metastases. These cytokines are thought to contribute to pain by sensitization of peripheral nociceptors. NSAIDs and steroids are postulated to reduce pain from bony metastases by inhibition of the cyclooxygenase pathway of arachidonic acid breakdown, thus decreasing the formation of PGE 2 . As deposits enlarge, stretching of the periosteum, pathologic fractures, and perineural invasion contribute to the pain, and requirements for analgesics increase. Palliative radiation therapy is used successfully to relieve pain emanating from bony metastases. However, pain relief may not be seen in 100% of cases. Thus, other forms of therapy may need to be implemented.
Vertebral body metastases are associated with carcinoma of the lung, breast, and prostate. Localized paraspinal, radicular, or referred pain within the dermatomal distribution of the affected nerve structure is usually the first sign of metastasis to the spine. It is often manifested as severe local, dull, steady, aching pain and is frequently exacerbated by movement and weight bearing. On physical evaluation, local midline tenderness may be present, as well as corresponding neurologic changes associated with either nerve compression or epidural–spinal cord compression. Invasion of the second cervical vertebra may result in pain referred to the occiput, and C7-T1 invasion may produce interscapular pain.
Base of Skull Metastasis
Metastasis to the base of the skull is usually accompanied by headache and a spectrum of neurologic findings, especially when the cranial nerves are involved. Symptomatic metastasis to the skull is usually, but not always, a late finding. Plain radiography, scintigraphy, and computed tomography (CT) are helpful for the diagnosis of bony disease, whereas MRI and lumbar puncture are useful in evaluating soft tissues and detecting leptomeningeal disease, respectively.
Musculoskeletal pain in the form of myofascial pain is frequently seen in cancer patients. Patients with bone metastases and those with post–radical neck dissection syndrome are frequently affected by this condition. Stress, anxiety, muscle overuse to compensate for the lack of bone support, or the absence of other muscles resected during cancer surgery may play an important role in the development of this condition. Thus, treatment should be multidisciplinary and include pharmacologic therapy, trigger point injections, and physical rehabilitation with the use of orthotic devices as needed.
Leptomeningeal Metastasis, Meningeal Carcinomatosis
These conditions are frequently seen with primary malignancies of the breast and lung and with lymphoma and leukemia; it is secondary to diffuse infiltration of the meninges. About 40% of patients have headache or back pain, presumably caused by traction on the pain-sensitive meninges or traction on cranial or spinal nerves or secondary to raised intracranial pressure. Headache is the most common initial complaint; it is characteristically unrelenting and may be associated with nausea, vomiting, nuchal rigidity, and changes in mental status. Neurologic abnormalities may include seizures, cranial nerve deficits, papilledema, hemiparesis, ataxia, and cauda equina syndrome. The diagnosis may be suggested by the T2 phase of MRI, and it is usually confirmed via lumbar puncture and cerebrospinal fluid (CSF) analysis, which typically shows elevated protein and decreased glucose, as well as malignant cells. The natural history of patients with leptomeningeal metastasis is a gradual decline and death over a period of 4 to 6 weeks, although survival is often extended to 6 months or more when radiation therapy or intrathecal chemotherapy (or both) is instituted. Steroids may be useful in the management of headache, as well as the neuropathic pain associated with spinal cord and nerve involvement.
Spinal Cord Compression and Plexopathies
Spinal cord compression is usually heralded by pain in the presence of neurologic changes. An urgent radiologic workup is mandatory in patients with neurologic deficits, particularly motor weakness, bandlike encircling pain, or incontinence. Prompt treatment in the form of radiotherapy or spinal stabilization and high-dose IV steroids may limit the neurologic morbidity.
Plexopathies are the result of tumor growth around nerve plexuses in the upper or lower extremity. Cervical plexopathy is most commonly due to local invasion by head and neck cancer. Symptoms include aching preauricular, postauricular, or neck pain. Brachial plexopathy is most commonly caused by upper lobe lung cancer (Pancoast syndrome or superior sulcus syndrome), breast cancer, or lymphoma. Pain is an early symptom that usually precedes the neurologic findings by up to 9 month s. The lower cord of the plexus (C8-T1) is affected most frequently, and pain is usually diffuse and aching and radiates down the arm, often to the elbow and medial (ulnar) aspect of the hand. When the upper part of the trunk is involved (C5-6), pain is generally found in the shoulder girdle and upper portion of the arm and radiates to the thumb and index finger. Horner’s syndrome, dysesthesias, progressive atrophy, and neurologic impairment (weakness and numbness) may occur. Brachial plexus invasion may be associated with contiguous spread to the epidural space. Lumbosacral plexopathy may be due to local soft tissue invasion or compression from tumors of the rectum, cervix, or breast, sarcoma, and lymphoma; pain is usually the initial symptom in 70% of such patients. The pain is usually described as aching or pressure-like and only rarely is dysesthetic. Depending on the level involved, pain is referred to the low back region, abdomen, buttock, or lower extremity. This medical problem must be differentiated from spinal cord invasion or cauda equina syndrome, for which urgent diagnosis and treatment are mandatory. Clinical experience shows that brachial plexopathies respond better to medical therapy with opioids, tricyclic antidepressants, and anticonvulsants, whereas lumbosacral plexopathies may require early intervention with intrathecal opioid, bupivacaine, and clonidine therapy.
Pain Associated with Cancer Treatment
Oral mucositis typically occurs within 1 to 2 weeks of the initiation of chemotherapy. This condition is most common with the use of methotrexate, doxorubicin, daunorubicin, bleomycin, etoposide, 5-fluorouracil, and dactinomycin. Mucositis is often most severe when chemotherapy is combined with radiation treatments involving the head and neck region. Treatment may require hospitalization for IV PCA opioid therapy. Ambulatory care may necessitate transdermal opioids, local anesthetics, or doxepin swishes.
Painful polyneuropathy occurs most commonly with vincristine (motor and sensory involvement), vinblastine, paclitaxel, docetaxel, a platinum derivative (predominantly sensory involvement), vinorelbine, and bortezomib. Symptoms commonly include burning dysesthetic pain in the hands and feet. The majority of these patients will respond to medical therapy with opioids, tricyclic antidepressants, and anticonvulsants. However, the small number of patients who do not achieve adequate pain control with this strategy will usually show a significant response to the use of spinal cord stimulation.
Postsurgical chronic pain syndromes are most common after mastectomy, thoracotomy, radical neck dissection, nephrectomy, and amputation. The clinical characteristics generally include aching, shooting, or tingling pain in the distribution of peripheral nerves (e.g., intercostobrachial, intercostals, cervical plexus), with or without skin hypersensitivity. One study suggested that the incidence of post-mastectomy pain was higher after conservative surgery than after modified radical mastectomy (33% vs. 17%). In this same study, 25% of patients experienced postoperative phantom breast pain. The exact incidence of postsurgical pain syndromes is unclear but appears to be in the 25% to 50% range by some estimates. Medical therapy with opioids, tricyclic antidepressants, and anticonvulsants is successful in the great majority of patients. Those who fail pharmacologic therapy will benefit from intrathecal therapy (post-thoracotomy, post-mastectomy syndromes), spinal cord stimulation (post-thoracotomy, post-mastectomy syndromes), or even peripheral subcutaneous nerve stimulation (post–radical neck dissection, post-thoracotomy syndromes).
Headache is present in 60% of patients with a primary or metastatic brain tumor, half of whom classify it as their primary complaint. It is typically steady, deep, dull, and aching with moderate intensity and is rarely rhythmic or throbbing. It is usually intermittent and may be worse in the morning and with coughing or straining. Symptoms often improve with radiation therapy, NSAIDs, or corticosteroids.
Cervicofacial pain syndromes are most common in patients with head and neck cancer. The head and neck are richly innervated by contributions from cranial nerves V, VII, IX, and X and the upper cervical nerves, so the pain varies in character. When cranial nerves are involved, the symptoms represent those of trigeminal, glossopharyngeal, or intermittent neuralgia, with sudden, severe lancinating pain radiating to the face, throat, or ear, respectively. The pain may be accompanied by dysesthesias, trigger points, and impaired swallowing, breathing, and phonation. Pharmacologic therapy with opioids, tricyclic antidepressants, and anticonvulsants is useful in the great majority of these patients. In those whom pharmacologic therapy fails, radiofrequency lesioning of the sphenopalatine or gasserian ganglion may be useful.
Radiation therapy may be associated with both acute and chronic pain syndromes. Acutely, mucositis and cutaneous burns may be seen. Chronically, postradiation syndromes include osteoradionecrosis, myelopathy, plexopathy, soft tissue fibrosis, and the emergence of new secondary neurogenic tumors.
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