Cancer Pain
Richard T. Lee
Michael J. Fisch
It is likely that 85% of patients with cancer could be free of significant pain with the techniques we have available today. Most pain from cancer can be adequately controlled with analgesics given by mouth. When this is not possible, various more sophisticated pain management techniques can provide good pain control. Unfortunately, poorly controlled pain and/or analgesic side effects have significant effects on the quality of life of patients and their families. For example, symptoms such as depressed mood, fatigue, anorexia, and sleep disturbance are associated with poor pain control. Likewise, opioid side effects may cause chronic nausea, anorexia, constipation, dehydration, sedation, and confusion. Consequently, over-all performance status and adherence to anticancer treatment regimens may deteriorate in the presence of poor pain management. Desperate patients and families may seek relief through unproven therapies or even from physician-assisted suicide. Improving the practice of anticipating, evaluating, and treating pain will benefit most patients.
I. PREVALENCE, SEVERITY, AND RISK FOR PAIN
Most cancer patients with terminal disease need expert pain management. Between 60% and 80% of such patients have significant pain at some point in their trajectory of illness, and nearly 20% of oncology
outpatients have moderate to severe pain at any given outpatient visit. Sometimes, chronic pain will be expressed by the patient in confusing terms (“stiffness,” “nagging”) or masquerade as other symptoms (fatigue, apathy, anxiety, anorexia). For this reason, the estimates of the prevalence and impact of chronic pain in this population are probably conservative. Nevertheless, in the United States, 60% of all outpatients with metastatic disease have cancer-related pain, and one-third report pain so severe that it significantly impairs their quality of life. Multicenter studies indicate that about 40% of outpatients with cancer pain do not receive analgesics potent enough to manage their pain, especially among minority patients, female patients, and older patients.
II. ETIOLOGY OF CANCER PAIN
A. Direct tumor involvement
This is the most common cause of pain and is present in about two-thirds of those with pain from metastatic cancer. Tumor invasion of bone is the physical cause of pain in about 50% of these patients. The remaining 50% of patients experience tumor-related pain that is due to nerve compression, tumor infiltration, or involvement of the gastrointestinal tract or soft tissue.
B. Persistent pain after treatment
Persistent pain from long-term effects of surgery, radiotherapy, and chemotherapy accounts for an additional 20% of all who report pain with cancer, with a small residual group experiencing pain from non-cancer-related conditions. Chronic pain is a common problem for cancer survivors with some studies indicating nearly a third reporting active pain symptoms.
C. Complex, chronic pain
Most patients with advanced cancer have pain at multiple sites caused by multiple mechanisms. Pain production occurs either by stimulation of peripheral pain receptors or by damage to afferent nerve fibers. Peripheral pain receptors can be stimulated by pressure, compression, and traction as well as by disease-related chemical changes. Pain due to stimulation of pain receptors is called nociceptive pain. Damage to visceral, somatic, or autonomic nerve trunks produces neurogenic or neuropathic pain. Neuropathic pain is thought to be caused by spontaneous activity in nerves damaged by disease or treatment. Patients with cancer often simultaneously experience nociceptive and neuropathic pain. In addition to evaluating the broad possible causes of pain production, the evaluating clinician should also consider the relevant mechanisms of pain perception and expression. Pain perception refers to the transmission of the nociception to the central nervous system (CNS). Peripheral nerve fibers include myelinated Aδ fibers that are responsible for the transmission of sharp pain and unmyelinated C fibers that carry dull and burning pain. These primary sensory afferents have their
cell bodies in the dorsal horn, where the pathways decussate and ascend along the spinothalamic tracts to the thalamus and cortex. Repetitive or continuous stimulation of the peripheral nerves can increase the excitability of the secondary neurons and spread the neurologic region of pain perception and transmission. The N-methyl-D-aspartate (NMDA) receptor is involved in the neurobiology of this “wind-up” phenomenon as well as in the development of tolerance to opioid analgesics. Understanding this biology of pain perception helps account for the observation that some patients experience pain that endures even after the tumor or injury has resolved, and sometimes the pain is more severe than one might expect from the nerve or tissue insult itself. Of course, the clinician can directly observe only pain expression; the production and perception of the pain can be inferred only from indirect clues. Pain expression, that is, how patients report or show their pain, can be influenced by multiple factors (mood, cultural beliefs, etc.). For this reason, effective pain assessment and management necessitates a comprehensive understanding of the patient as a person.
III. ASSESSMENT OF PAIN
Proper pain management requires a clear understanding of the characteristics of pain production, perception, and expression, as described previously. The changing expression of cancer pain demands repeated assessment because new causes of pain can emerge rapidly and pain severity can increase quickly. In patients with advanced disease, pain from multiple causes is the rule and not the exception. A careful history includes asking questions concerning the location, severity, and quality of the pain as well as the aspects of the patient’s daily routine that may be adversely affected by the pain experience.
Health professionals should also consider a comprehensive evaluation of pain that incorporates several dimensions of health including physical, psychospiritual, and sociocultural. Just as pain may affect patients’ moods, anxiety or depression also has been shown to alter patients’ perception of pain. Additionally, sociocultural differences in the meaning of pain will alter how patients experience and express their pain symptoms. Identifying these key factors will assist with successful pain management.
A. Pain severity
Inadequate pain assessment and poor physician-patient communication about pain are major barriers to good pain care. Physicians and nurses tend to underestimate pain intensity, especially when it is severe. Patients whose physicians underestimate their pain are at high risk for poor pain management and compromised function. A small minority of patients with cancer may complain of pain in a dramatic fashion, but many more patients underreport the severity of their pain and the lack of adequate pain relief.
Several studies have confirmed that there are multiple reasons for this hesitancy to report pain, including the following:
▪ Reluctance to acknowledge that the disease is progressing
▪ Reluctance to divert the physician’s attention from treating the disease
▪ Reluctance to tell the physician that pain treatments are not working.
Patients may not want to be put on opioid analgesics because of the following reasons:
▪ Fear of addiction
▪ Concern about possible neurotoxic side effects of opioids (sedation, confusion)
▪ Frustration over gastrointestinal side effects of opioids (nausea, constipation, anorexia)
▪ Fear that using opioids “too early” will endanger pain relief when they have more pain
▪ Fear that opioid use means that death is near
▪ Having accepted religious or societal norms or teachings that pain should be endured.
Presenting information that addresses these concerns in a straightforward manner will allay most of these fears and should be considered as an essential step in providing pain control. It is important that patients understand that they will function better if their pain is controlled and their opioid side effects are prevented or managed effectively. Patient education materials available from state cancer pain initiatives and from the National Cancer Institute (www.cancer.gov), the American Cancer Society (www.cancer.org), the National Comprehensive Cancer Network (NCCN; www.nccn.org), and the American Society of Clinical Oncology (www.cancer.net) can be very useful for both patients and families and should be given to patients when they develop pain.
Communication about pain is greatly aided by having patients use a scale to rate the severity of their pain. A simple rating scale ranges from 0 to 10, with 0 being “no pain” and 10 being pain “as bad as you can imagine.” Used properly, pain severity scales can be invaluable for titrating analgesics and monitoring increases in pain with progressive disease. Mild pain is often well tolerated with minimal impact on a patient’s activities. However, there is a threshold beyond which pain is especially disruptive. This threshold has been reached when patients rate the severity of their pain at 5 or greater on a 0 to 10 scale. When pain is too great (7 or greater on this scale), it becomes the primary focus of attention and compromises most activities that are not directly related to pain. Although it may not be possible to eliminate pain totally, reducing its severity to 4 or less should be a minimum standard of pain therapy.
Often, patients may have difficultly relating to a scale of 0 to 10 or communication may be limited due to neurologic deficits. When initially assessing pain, asking what pain level is tolerable to them may assist with a goal pain score. Other times, patients may indicate only minimal changes in their pain score while showing signs of significant improvement. Rather than using the 0 to 10 scale, others may respond better to mild, moderate, or severe while others may be better able to describe differences in pain by stating by what percentage the pain has changed. When communication is limited, questions may focus on behaviors such as sleep, the provider may ask family members about changes in behavior or irritability, or the provider may consider nonverbal cues such as wrinkling of the forehead. Providing patients with different ways in which to express their pain score as well as the provider’s ability to collect information will assist with assessing treatment interventions.
In some instances, patients may develop chronically high levels of pain expression that do not respond to appropriate initial analgesic dosing and coprescribing of medications to prevent nausea and constipation. The proper care of this subset of patients often requires a multidisciplinary approach; it includes regular administration of pain medication plus counseling and sometimes use of antidepressants or anxiolytic agents. Skillful switching of opioid medications (often called “opioid rotation” or “opioid switching”) can produce a more favorable ratio of analgesia to opioid side effects. Interventional pain procedures may be appropriate in selected cases as well. Such procedures may include nerve blocks (such as a celiac plexus block) or neuraxial delivery of opioids and other adjuvant medications (such as epidural or intrathecal therapies).
B. Diagnostic steps
Those who treat patients with cancer should be familiar with the common pain syndromes associated with the disease:
1. Having the patient show the area of pain on a drawing of a human figure aids identification of the syndrome. This can be particularly helpful in indicating areas of referred pain that commonly coincide with nerve compression.
2. Careful questioning concerning the characteristics of the pain is a key component of diagnosis. For example, pain characterized as “burning” or “shooting” may indicate neuropathic pain.
3. In addition to severity, these characteristics include the temporal pattern of the pain (constant or episodic) and its quality. Episodic or “incident” pain (such as severe pain when standing) requires a different strategy for management than chronic pain.
4. Other important characteristics of pain are its relationship to physical activity and what seems to alleviate the pain.
5. The physical examination includes examination of the painful area as well as neurologic and orthopedic assessment. A brief assessment of mood and cognition is also appropriate. Impaired cognition can confound symptom assessment dramatically.
6. Because bone metastases are a common cause of pain and pain can occur with changes in bone density that is not detectable on radiographs, bone scans can be helpful. Magnetic resonance imaging (MRI) is useful in the evaluation of retroperitoneal, paravertebral, and pelvic areas as well as the base of the skull.
C. The impact of pain on the patient
When pain is of moderate or greater severity, one can assume that it has a negative impact on the patient’s quality of life. That impact, including problems with sleep and depression, must be evaluated and treated when appropriate. A reduced number of hours of sleep compared with the last pain-free interval, difficulties with sleep onset, frequent interruptions of sleep, and early morning awakening suggest the need for appropriate pharmacologic intervention. Just as patients hesitate to report severe pain, they may hesitate to report depression. Family caregivers can often provide important clues regarding the presence or absence of a mood disturbance. Significant depression should be treated. Treatment approaches may include use of antidepressants, counseling, and/or referral to a behavioral health specialist. Sometimes a patient will accept only one of the suggested options, thus requiring some degree of flexibility on the part of the clinician in order to achieve the best results.
It is important to make an attempt to differentiate between physical pain and psychological distress. Accurate pain assessment in patients who are cognitively impaired, particularly those with agitation, may be extremely difficult. A small number of patients in severe psychosocial distress express their concerns as a report of physical pain. These patients present with symptoms that may be attributable to either agitated delirium or pain. Although it is important to recognize severe somatization and to provide psychiatric referral or counseling to these patients, it is equally important to recognize true physical pain. Because of the possible misinterpretation by patients that the medical establishment is atrributing their pain as entirely psychological in nature, a frank discussion with patients regarding the difficulty many patients have distinguishing between physical and emotional pain, which often occur together, may help patients understand your approach and often provide an opportunity to acknowledge different sources of pain they may not have considered. Ultimately, the treatment approach for this difficult situation includes concomitant provision of pain treatment(s) and management of the patient’s underlying psychological distress.
D. Addiction/aberrant drug-taking behaviors
Some patients with alcohol or drug addiction may request analgesics for their psychological effects or may have aberrant drugtaking behaviors. Aberrant drug-taking behaviors may include requests for frequent, early renewals; unauthorized dose escalations; reports of lost or stolen prescriptions; adamant requests for specific medications; and acquisition of similar drugs from other medical sources. Patients with past or current substance use disorders may also be difficult to treat because of fear of exposure to opioid analgesics and their potential vulnerability to addiction. In any case, these behaviors or fears should be discussed openly and in nonjudgmental terms with the patient. Ultimately, an agreement should be reached about the use of opioids for the management of pain (as opposed to mood alterations), and some details about the expectations and responsibilities of both the physician and the patient should be delineated. With this group of patients, long-acting opioids or continuous infusion is often preferable to short-acting opioids or patient-controlled analgesia. Although their care is more complex, patients with drug or alcohol addiction should not be denied appropriate pain medications.
IV. TREATMENT
A. General aspects
All healthcare professionals who see patients with cancer should be familiar with standard guidelines for management of cancer pain such as those published by the NCCN or the Agency for Healthcare Research and Quality. An example of a cancer pain practice guideline is shown in Table 31.1. This guideline incorporates basic principles of cancer pain assessment, initial treatment, and routine management of opioid side effects.
The prompt relief of pain from cancer frequently involves the use of simultaneously rather than serially administered combinations of drug and other adjunctive therapies. Identification of a treatable neoplasm as a factor in pain production calls for appropriate radiotherapy (e.g., to bone metastases), chemotherapy, or, in some instances, surgical debulking. Until such treatment can be effective (this may take days to weeks), the patient’s pain must be managed with analgesics with or without other specific interventional pain procedures. In some instances, analgesics are the only effective palliative treatment available because of the patient’s condition, the physical basis of the pain, or limited treatment options. The principles of pharmacologic management of pain are evolving through studies of analgesic effectiveness and research on the use of combinations of palliative medications.
There is a growing consensus concerning the types of drugs to use, their routes of administration, and how best to schedule them. The first step is to assess the severity of the pain. Simple categories such as mild, moderate, and severe are often sufficient. Second is the choice of analgesic drug to be used (nonopioid, opioid, or a combination of both), which is commonly based on the severity level. The next step is the choice of adjuvant drugs, which can increase analgesic effectiveness and can produce other palliative effects to counter the disruptive consequences of pain. Finally, some consideration should be made on follow-up assessment of the interventions to ensure adequate relief is achieved.
TABLE 31.1 An Example of a Pain Practice Guideline
A. Comprehensive pain assessment
1. Evaluation of pain. Determine level using 0-10 intensity scale, location, onset, duration, frequency, quality (somatic, visceral, neuropathic), history, etiology, associated symptoms, what modifies the pain, side effects associated with treatment of pain, and response to other pain medications. No pain (0) Mild (1-3) Moderate (4-6) Severe (7-10)
2. Evaluation of past medical history (oncologic or other significant medical illnesses) including medication history
3. Physical examination
4. Evaluation of relevant laboratory and imaging studies
5. Evaluation of risk factors for undertreatment of pain, including underreporting, extremes of age, gender, cultural barriers, communication barriers, and a history of substance abuse
6. Evaluation of psychosocial issues (patient distress, family support, psychiatric history, special issues relating to pain [meaning of pain for patient/family, patient/family knowledge of and beliefs surrounding pain])
B. Overall management plans
1. If pain = 0, reassess at each subsequent visit or interaction
2. Manage pain related to oncologic emergencies, if any
a. Such pain requires assessment and treatment (e.g., surgery, steroids, radiotherapy, antibiotics) along with an emergent consultation
b. Oncologic emergencies include:
▪
Bowel obstruction/perforation
▪
Brain metastasis
▪
Leptomeningeal metastasis
▪
Fracture or impending fracture of weight-bearing bone
▪
Epidural metastasis/spinal cord compression
▪
Pain related to infection.
3. Manage non-emergency-related pain
C. Management of non-emergency-related pain
1. If pain = 1-3
▪
NSAIDs (including COX-2 agents) and acetaminophen. If ineffective: opioids (hydrocodone scheduled or as needed)
▪
Overall reassessment at each subsequent visit or interaction.
2. If pain = 4-6
▪
Oral opioids
▪
Morphine 15 mg orally every 4 hours as needed or scheduled
▪
Oxycodone 5 mg orally every 4 hours as needed or scheduled
▪
Hydromorphone 2 mg orally every 4 hours as needed or scheduled
▪
Adjuvants: NSAIDs, antidepressants, antiepileptics, etc.
▪
Overall reassessment in 24-48 hours.
3. If pain = 7-10 (possible pain crisis)
▪
Oral opioids: morphine 20 mg orally every 4 hours as needed (opioid-naive)
▪
Thirty percent increase in current opioid regimen (sustained- and immediate-release [rescue] opioids)
▪
Morphine, hydromorphone, or oxycodone for rescue dosing
▪
Consider intravenous opioid titration (PCA pump may be used to titrate)
▪
Reassess frequently, based on clinical situation.
D. Additional steps for pain that was rated 4-10
1. Re-evaluate opioid titration
2. Re-evaluate pain diagnosis
3. Consider consults from specialty services*
4. All patients receiving opioids should begin:
▪
Bowel regimen (such as oral senna 1 tablet twice daily)
▪
Antiemetics as needed (such as metoclopramide 10 mg 30 minutes before meals and at bedtime)
▪
Educational activities regarding pain management
▪
Psychosocial support as needed.
E. At the time of re-evaluation for patients whose pain was 4-10
1. If pain now = 1-3
▪
Consider conversion to a sustained-release agent with rescue medications
▪
Continue adjuvants or add them as needed
▪
Reassess and modify side effects of pain treatment
▪
Provide psychosocial support
▪
Provide educational activities
▪
Reassess pain every week until comfortable, then every visit.
2. If pain now = 4-6
▪
Continue opioid titration
▪
Consider specific pain problems
▪
Consider consults from specialty services*
▪
Continue psychosocial support
▪
Continue educational activities.
3. If pain now = 7-10† (possible pain crisis)
▪
Continue opioid titration
▪
Re-evaluate working diagnosis
▪
Consider specific pain problems
▪
Obtain consults from specialty services*
▪
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