Pain and Symptom Control
Russell K. Portenoy
Craig D. Blinderman
Introduction
Approximately 30% to 50% of cancer patients undergoing antineoplastic therapy and 75% to 90% of patients with advanced disease have chronic pain severe enough to warrant opioid therapy (1,2,3). Symptoms other than pain are also highly prevalent in this population, particularly when the disease is advanced (4). Unfortunately, there are numerous obstacles to effective pain and symptom management, and symptom distress caused by inadequately treated pain and other problems is commonly encountered in practice. These obstacles relate to deficiencies in clinician knowledge and skills, health care systems that limit access to care, and the tendency to underreport pain on the part of patients. To improve patient outcomes, strategies are needed to address these obstacles. Clinician education must focus on both the assessment of pain and other symptoms, and the many approaches that now exist to manage it.
Definitions and Models of Care
Pain, Nociception, and Suffering
According to the International Association for the Study of Pain, pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (5). To clarify the approach to pain assessment, it is useful to distinguish pain from both nociception and suffering.
Nociception is the activity produced in the afferent nervous system by potentially tissue-damaging stimuli. Nociception is clinically inferred whenever tissue damage is identified. Pain is the perception of nociception and can be sustained in the absence of ongoing tissue injury by any of a variety of factors. Neuropathic pain syndromes are presumably sustained through plastic changes in the nervous system; so-called psychogenic pains are attributed to psychological disturbances.
Suffering has been described as any threat to the integrity of the person and may be due to unrelieved symptoms (including pain), psychological or psychosocial disturbances, or spiritual distress (6,7). Other factors, such as financial concerns, may also be prominent. Patients vary in psychosocial and spiritual strengths and weaknesses, and consequently suffer in different ways when dealing with symptoms or other experi ences.
Supportive Care and Palliative Care
It is best to define supportive care as those interventions that are intended to manage the adverse effects of antineoplastic therapy. From this perspective, supportive care includes the use of blood products, growth factors, antibiotics, symptom management approaches, and interventions that address the psychosocial consequences of therapy.
The World Health Organization (WHO) has defined palliative care as “an approach that improves the quality of life of patients and their families facing … life-threatening ill ness … [palliative care relieves] suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual” (8). Palliative care is relevant throughout the course of the illness and must intensify as the end of life approaches. Its goals include symptom control; effective communication among patient, family, treatment team, and others; management of psychological distress and comorbid psychiatric disorders; and support for efforts to address social isolation and spiritual distress. Palliative care recognizes the need to provide practical support in the home and to manage caregiver distress and burden. For the patient with advanced illness, palliative care strives to remove the obstacles to a comfortable and dignified death, and to assist families in the process of effective grieving through support and formal bereavement services.
Palliative care should be considered an essential element in oncology practice. The routine efforts of the oncologist and other members of the oncology treatment team to address a broad array of patient concerns may be considered “generalist-level” palliative care. When distress continues despite this care, the oncologist typically refers the patient for specialist services. Specialist-level palliative care may be accessed through institution-based programs and, for eligible patients, hospice patients. In the United States, hospice and palliative medicine will soon be a formal subspecialty of medicine and other medical specialties, and will be largely provided by certified physicians who work in teams maintained through institutions or hospices. Recognition of the need for specialist-level palliative care and appropriate referral to a specialist team should be considered a necessary competency of oncologists and others who treat populations with progressive incurable disease.
Assessment and Management of Cancer Pain
Pain is a prevalent and distressing symptom, and is often considered the model for guidelines that have been developed to
assist in the management of other cancer-related symptoms. For most patients, multidimensional assessment, followed by simple management strategies, can yield satisfactory control of pain.
assist in the management of other cancer-related symptoms. For most patients, multidimensional assessment, followed by simple management strategies, can yield satisfactory control of pain.
Pain Characteristics
The pain complaint should be characterized in terms of clinically relevant descriptors: temporal features, location and patterns of radiation, intensity, quality, and factors that provoke or alleviate the pain. This information, combined with the physical examination and imaging studies, may identify a specific pain syndrome and allow inferences regarding the underlying pathophysiology.
Acute pain usually has a well-defined onset and a readily identifiable cause (e.g., surgical incision). If it is associated with other features, these usually are anxiety, moaning or grimacing, and signs of sympathetic hyperactivity (including tachycardia, hypertension, and diaphoresis).
In contrast, chronic pain is characterized by an ill-defined onset and a prolonged, fluctuating course. Overt pain behaviors and sympathetic hyperactivity are typically absent, and vegetative signs, including lassitude, sleep disturbance, and anorexia, may be present. A clinical depression evolves in some patients.
Most patients with chronic cancer pain also experience periodic flares of pain, or “breakthrough pain” (9). An important subtype of breakthrough pain is “incident pain,” which is precipitated by voluntary activity. The recognition of breakthrough pain as a significant problem has supported the use of so-called “rescue” doses—a short-acting opioid administered on an as-needed basis—during long-term opioid therapy.
Etiology and Inferred Pathophysiology
In most patients with cancer, pain can be related to an underlying nociceptive lesion, usually direct invasion of pain-sensitive structures by the neoplasm (10). Bone injury is most common, but pain can also occur as a result of damage to neural tissue, obstruction of hollow viscus, distention of organ capsules, distortion or occlusion of blood vessels, and infiltration of soft tissues. The etiology of pain relates to an antineoplastic treatment in about one fourth of patients, and fewer than 10% have pain unrelated to the neoplasm or its treatment (10). Identification of the etiology of the pain can provide an opportunity for a primary therapy, such as radio therapy (11).
The history, findings on examination, and objective data may allow inferences about the pathophysiological processes that may be sustaining the pain. These processes are categorized as nociceptive, neuropathic, psychogenic, idiopathic, or mixed. Although these labels represent constructs, they are clinically relevant, in many cases suggesting the use of specific therapies.
Nociceptive pain refers to pain that is sustained predominantly by ongoing tissue injury and may involve either somatic or visceral structures. Somatic pain is often described as aching, stabbing, throbbing, or pressurelike. Visceral pain is usually gnawing or crampy when arising from obstruction of a hollow viscus and aching or stabbing when arising from other visceral structures.
Pain is labeled neuropathic if the evaluation suggests that it is sustained by abnormal somatosensory processing in the peripheral or central nervous system. Neuropathic mechanisms are involved in approximately 40% of cancer pain syndromes and can be caused by disease or treatment (12). Dysesthesia, or abnormal uncomfortable sensations that may be described using words such as “burning,” “shocklike,” and “electrical,” are suggestive of neuropathic mechanisms. On physical examination, the presence of allodynia (pain induced by nonpainful stimuli) and hyperalgesia (increased perception of painful stimuli) also suggests this diagnosis. Patients may or may not develop motor or autonomic dysfunction in the distribution of the involved nerve.
Table 13.1 Acute pain syndromes in cancer patients | ||
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The term psychogenic pain refers to pain that is believed to be sustained predominantly by psychological factors and is a generic label applied to a number of syndromes described in the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association. An assessment of these pains should reveal positive evidence for the psychopathology that is believed to be causally related to the pain. Although psychological factors commonly influence the presentation of the pain and the patient’s adaptation, psychogenic pain appears to be rare in the cancer population.
In the absence of sufficient evidence to label the pain by a more definitive term, it can be considered idiopathic. In the cancer population, this label usually suggests the need to reassess etiology and pathophysiology at a later time.
Cancer Pain Syndromes
Efforts to improve the assessment of cancer pain have been greatly encouraged by the description of numerous pain syndromes, each of which is defined by a cluster of symptoms and signs (10,12). Syndrome identification can help direct the diagnostic evaluation, clarify the prognosis, and target therapeutic interventions.
Acute pain syndromes are commonly caused by diagnostic or therapeutic interventions, including surgery (Table 13.1). Chronic pain syndromes may be directly related to the neoplasm or to antineoplastic therapy (Tables 13.2 and 13.3).
Table 13.2 Chronic pain syndromes in patients with cancer: tumor-related pain syndromes | ||
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Table 13.3 Chronic pain syndromes in patients with cancer: treatment-related pain syndromes | ||
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Management of Chronic Cancer Pain
Role of Primary Therapy
Primary treatments for the pain include antineoplastic therapies and interventions directed at other pathologies. Although the palliative role of chemotherapy is widely accepted (13,14,15), the specifics have received limited study. Nonetheless, it is a common observation that patients who attain a partial or complete tumor response also experience symptom improvement. Two chemotherapies, mitoxantrone for prostate cancer and gemcitabine for pancreatic cancer, received regulatory approval largely on the basis of symptom palliation.
Radiation therapy has been reported to provide effective palliation of pain in up to 50% of patients treated for bone metastases (16,17), and pain control is the reason for treatment in the majority of patients who receive this intervention. Analgesia also commonly results when radiation is used to treat other disorders, including epidural disease, tumor ulceration, cerebral metastases, superior vena cava obstruction, and bronchial obstruction. Patients with limited prognosis (i.e., months) may benefit from single doses or a shortened fractionation schedule, thereby decreasing treatment burden (18).
Pharmacotherapy of Chronic Cancer Pain
Although primary therapies can be helpful in selected patients, most patients require symptomatic analgesic therapy.
Prospective trials indicate that 70% to 90% of patients can achieve adequate relief of cancer pain using a pharmacologic approach (3,19,20). Effective pain management requires expertise in the use of the nonsteroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, and the so-called adjuvant analgesics.
Prospective trials indicate that 70% to 90% of patients can achieve adequate relief of cancer pain using a pharmacologic approach (3,19,20). Effective pain management requires expertise in the use of the nonsteroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, and the so-called adjuvant analgesics.
A model approach to the selection of analgesic drugs for cancer pain, known as the “analgesic ladder,” was developed in the 1980s by an expert panel for WHO (3). Although the analgesic ladder approach has evolved since it was created and rigid adherence to its guidelines is no longer justified, key elements are still accepted. Most important, the approach reinforces the consensus view that persistent moderate to severe cancer pain should be treated with an opioid-based drug regimen. From this perspective, the analgesic ladder has been useful as a tool to educate policy makers and others about the need for access to opioids.
Nonsteroidal Anti-inflammatory Drugs
NSAIDs have a well-established role in the treatment of cancer pain (21). A recent meta-analysis suggests that NSAIDs can be effective initial monotherapy for cancer pain and that NSAIDs combined with opioids may lead to a slight short-term improvement in pain compared with either agent alone (22). The long-term efficacy and safety of NSAIDs for cancer pain have not been established.
In practice, a NSAID may be used as the sole analgesic for patients with generally mild pain and should be considered for combination therapy when pain is moderate or severe. NSAIDs appear to be especially useful in patients with nociceptive pain, particularly bone pain and pain related to grossly inflammatory lesions, and relatively less useful in patients with neuropathic pain (23,24,25). Recent studies in the neurobiology of bone pain suggest that there may be an even greater role for NSAIDs in managing pain secondary to bony metastases (26,27,28).
The therapeutic limitations of NSAIDs are primarily due to their side effects. All NSAIDs have the potential for nephrotoxicity, with effects that range from peripheral edema to acute or chronic renal failure. Clinical effects and serum creatinine must be monitored periodically in the medically frail cancer patient who receives one of these drugs for ongoing treatment of pain. In addition, NSAIDs increase the risk of gastrointestinal ulcers and bleeding. The selective cyclo-oxygenase (COX)-2 inhibitors reduced the risk of the latter outcomes, and many clinicians recommend these drugs as first-line therapy for all patients at relatively high risk of ulcer, including the elderly, those concurrently receiving a corticosteroid, those with a prior history of peptic ulcer disease or NSAID-induced gastroduodenopathy, and patients who are medically frail and less able to tolerate a gastrointestinal hemorrhage. Recently, there has been recognition that that COX-2 inhibition can increase the risk of thrombotic disease, and the U.S. Food and Drug Administration has required a special warning about this risk on the labels of all NSAIDs, including the nonselective COX inhibitors and the COX-2 selective drugs. Although this risk appears to be relatively small, it may influence the decision to offer a NSAID to patients at relatively high risk of thrombotic complications for other reasons.
Adjuvant Analgesics
The adjuvant analgesics are a diverse group of drugs, most of which have primary indications other than pain but can be effective analgesics in specific circumstances (29) (Table 13.4). Treatment with one of these drugs is generally considered if an optimally administered opioid regimen fails to provide a satisfactory balance between pain relief and side effects. These drugs are particularly useful in the treatment of neuropathic pain, bone pain, and pain related to bowel obstruction.
Corticosteroids are multipurpose adjuvant analgesics. In addition to their use in neuropathic pain, these drugs may improve anorexia, nausea, and fatigue associated with advanced cancer. They are empirically used to treat the pain associated with lymphedema, liver metastases, bowel obstruction, metastatic bone pain, headache associated with intracranial mass lesions, and superior vena cava syndrome.
Corticosteroids, anticonvulsants, antidepressants, and other drugs have analgesic effects in neuropathic pain (29). The safety and efficacy of gabapentin has been established in both nonmalignant (30,31) and cancer-related neuropathic pain syndromes (32,33,34), and this drug, or a similar, recently approved drug, pregabalin, is therefore usually tried first. Of the newer anticonvulsants, the evidence of analgesic efficacy is strongest for pregabalin, and there is also some evidence for lamotrigine; other anticonvulsants are tried empirically in refractory cases, despite limited supporting data.
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