Management of Cancer Pain

Definition of Pain and Anatomic CorrelatesManagementConclusionsReferences

The public fear that cancer is inevitably painful [1] is warranted: The majority of patients with advanced cancer and up to 60% of patients with any stage of disease will experience significant pain. The World Health Organization has estimated that 25% of all cancer patients die with unrelieved pain [2].

Leading oncologic organizations have stated that the relief of pain and other symptoms should be a priority in the care of these patients [3–6]. The benefits of adequate pain control include facilitation of the diagnostic workup and treatment, improved functional status, and better quality of life.

It has been demonstrated that most cancer patients' pain can be relieved adequately with oral analgesics [7,8]. Despite this, cancer pain is undertreated for a multitude of reasons. The problem is not trivial, because unrelieved pain is known to be a risk factor for suicide in cancer patients [9]. The Eastern Collaborative Oncology Group 1991 survey of oncologists revealed that physicians attribute undertreatment to their own lack of education and poor clinical role models [10]. Hill and others have outlined other influences, such as physicians' fear of regulatory agency scrutiny and fear of patient addiction [11,12]. Current efforts are directed at standardizing pain treatment [13] and separating issues of pain treatment from those of substance abuse. It is encouraging to note that a dialogue between addiction specialists and cancer pain specialists has begun to address these issues [14].

The effective management of cancer patients with pain is best accomplished in a multidisciplinary fashion with coordination of the services of oncologists, pain specialists, nurses, social workers, physiatrists, physical therapists, psychologists, psychiatrists, community health-care providers, clergy, and hospice workers [15]. Maintaining communication among members of the care-giving team is essential to providing optimal care.

Definition Of Pain and Anatomic Correlates

Pain has been defined as “a sensory and emotional experience associated with tissue damage or described in terms of such damage [16].” In humans, parallel neural pathways transmit information about painful stimuli from the periphery, through the spinal cord, to multiple areas of the brain. Pain signals (nociceptive inputs) are localized and interpreted and the affective component assigned at the cerebral cortical level. Modulation of nociceptive input by opioid and nonopioid mechanisms occurs in the periphery, at the dorsal horn of the spinal cord, in the brain stem, and possibly in higher centers.

Pathophysiology

The pathophysiologic classification of pain forms the basis for therapeutic choices. Pain states may be broadly divided into those associated with ongoing tissue damage (nociceptive) and those resulting from nervous system dysfunction in the absence of ongoing tissue damage (non-nociceptive or neuropathic). The pathophysiologic schema proposed by Portenoy is shown in Figure 1 [17].

FIGURE 1: Proposed taxonomy of chronic pain, based on presumed pathophysiology distinctions among nociceptive, neuopathic, and psychogenic pain. Adapted from Portenoy RK [17].

Damage to the nervous system may result in pain in an area of reduced sensation. Such pain is typically described as burning or lancinating. Patients may cite bizarre complaints, such as painful numbness, itching, or crawling sensations. The postamputation phenomenon of phantom pain (referred to the lost body part) may be disabling.

Care should be taken when considering the diagnosis of “psychogenic pain,” or somatoform pain disorder [18], because this type of pain is rare in cancer patients. More commonly, psychological factors affect the reporting of pain. It is also true that chronic unrelieved pain has psychological consequences, but this does not support a psychiatric basis for the pain complaint.

Pain Syndromes

Common cancer pain syndromes vary by tumor type and are related to patterns of tumor growth and metastasis. Pain may be directly related to antineoplastic therapy and may be indirectly related or unrelated to either the neoplasm or its treatment (Table 1)[2].

Due to invasion of nerves

Due to invasion of viscera
Due to invasion of blood vessels
Due to invasion of mucous membranes

Postchemotherapy pain syndromes

Postradiation pain syndromes

Management

Elements of cancer pain management include a proper medical evaluation, psychosocial assessment, formulation of the pain “diagnosis,” and consideration of pharmacologic and nonpharmacologic treatments. Ongoing care is needed to monitor the efficacy of analgesics and the evolution of different symptomatology during treatment or disease progression.

The steps in medical decision making are to: (1) determine whether primary antineoplastic therapy is indicated for palliation, (2) tailor pharmacologic analgesic therapy to individual needs, (3) consider concurrent nonpharmacologic analgesic methods, and (4) monitor the patient for response and modify treatment accordingly (Figure 2) [19]. The patient remains the focus of care, although family members and other concerned individuals often participate in treatment decisions and require emotional support.

FIGURE 2: Algorithm for the integration of management approaches to cancer pain. Adapted from Foley KM, Arbit E [19].

Patient Evaluation

The medical evaluation begins with a thorough history. Because there are no objective means with which to verify the presence of pain, one must believe a patient's complaint. The physiologic signs of acute pain-elevated blood pressure and pulse rate-are not reliable in verifying subacute or chronic pain. Most cancer patients report more than one site of pain [20]. A detailed history of each type of pain should be elicited (Table 2)[21]. As the chief complaint resolves, what was initially considered a secondary problem may require attention.

Pain-rating scales should be used to establish a baseline against which the success of treatment may be judged (Figure 3). Behavioral observations may be used to assess patients who are unable to communicate. Although there are standardized tools for preverbal children [22], they are not available for impaired adults. Therefore, it is sometimes necessary to treat pain presumptively.

FIGURE 3: Pain rating scales used to establish a baseline against which treatment results are judged.

The physical examination includes careful neurologic testing, especially if neuropathic pain is suspected. Pain in an area of reduced sensation, allodynia (ie, when normal stimuli are reported as painful), and hyperpathia or summation of painful stimuli support a neuropathic process.

The extent of disease and current medical conditions must be determined. Diagnostic tests should be reviewed and supplemented as necessary. Cancer treatment and prior analgesic interventions with their outcomes should be recorded. Psychological dependency on licit or illicit drugs, including alcohol, must be identified.

Psychosocial Assessment

To establish trust, the evaluating clinician should explore the significance of the pain complaint with the patient. The impact of pain and other symptoms on functional status must be understood to establish the goals of treatment. Suffering may be attributable to many factors other than physical complaints. The clinician should ask about such psychological factors as financial worries, loss of independence, family problems, social isolation, and fear of death. Often cancer patients meet the diagnostic criteria for the psychiatric diagnosis of adjustment disorder, with anxiety and/or depressed mood [23].

Patient Subgroups

It is useful to recognize distinct subgroups of patients (Table 3)[24]. To help define the goals of therapy, age, prognosis, and history of drug or alcohol abuse may be considered. Adjustments in drug dosages are usually needed for elderly patients who are more sensitive to analgesics and their side effects. Children may require relatively larger doses of opioids [25]. The use of chronic opioid analgesics requires special consideration in patients who are in long-term remission. Patients with substance-abuse problems who are receiving opioids for pain demand careful attention.

Acute pain associated with the diagnosis of cancer
Acute pain associated with cancer therapy, including surgery, chemotherapy, and radiation therapy

Chronic pain associated with cancer progression
Chronic pain associated with cancer therapy, including surgery, chemotherapy, and radiaton therapy

Actively involved in illicit drug use
In a methadone maintenance program
With a past history of drug abuse

Pharmacologic Treatment

The World Health Organization's three-step analgesic ladder outlines the use of nonopioid analgesics, opioid analgesics, and adjuvants for progressively severe pain (Figure 4).

FIGURE 4: Analgesic ladder outlining the use of nonopioid analgesics, opioid analgesics, and analgesic adjuvants for progressively severe pain. Adapted from World Health Organization: Cancer Pain Relief and Palliateve Care, Geneva, World Health Organization, 1990.

Nonopioid analgesics are associated with ceiling effects, and exceeding the maximum dose ranges can result in organ toxicity. Potential side effects, such as hematologic, renal, or gastrointestinal reactions, may be of clinical concern in cancer patients (Table 4)[26].

General guidelines for opioid therapy are outlined in Table 5 [27].

Analgesic type
Pharmacokinetics
Influences of coadministered drugs, disease, or age on analgesic disposition and response
Equianalgesic starting dose for the drug and route to be used
Route of administration and a dosage form to fit the patient's needs

The rules of opioid use are to: (1) individualize the agent, route, dose, and schedule; (2) titrate to efficacy; (3) provide for breakthrough pain; (4) anticipate and treat side effects; and (5) make conversions from one route to another or one agent to another by using known equianalgesic doses. Opioid agonists do not exhibit ceiling effects. Dosing is guided by efficacy and limited by side effects (Table 6)[26]. Dosages of tablets combining a nonsteroidal anti-inflammatory drug (NSAID) and an opioid are limited according to the NSAID.

The oral route of administration should be used when possible. If this is not feasible or systemic side effects are uncontrollable, alternative routes are indicated (Table 7) [26]. Spinal routes [28,29], both epidural and intrathecal, can be employed with internal delivery systems that allow patients to be fully ambulatory. Although in wide use, these methods have not been tested for cost-effectiveness. The spinal route should be considered if oral and other routes are unavailable or systemic therapy produces unacceptable side effects. Another advantage of spinal administration is that local anesthetic agents may be combined with the opioid to enhance analgesia at a lower total opioid dose.

Adapted, with permission, from American Pain Society [26].

The side effects of opioids can usually be anticipated and treated. In particular, laxatives should be prescribed with regular opioid dosing. Physical dependence and tolerance to some effects develop with chronic opioid use. Tolerance is likely to develop to respiratory depression, sedation, and nausea [27]. Tolerance to analgesia is not a major clinical problem and can usually be managed by changing the dose of an agent or substituting another agent [24]. Most current definitions of addiction imply a behavioral syndrome of compulsive, harmful use but do not require the existence of physical dependence or tolerance [30]. Iatrogenic addiction is not likely to occur in patients without a substance-abuse history [31].

During chronic opioid therapy, certain precautions should be observed. Normeperidine is a toxic metabolite of meperidine that accumulates with repetitive dosing; thus, the use of meperidine for chronic pain is limited. Placebo use is discouraged, because it does not help to distinguish the pathophysiology of pain. Physical withdrawal symptoms can be avoided by tapering doses. A changed mental status should not be attributed to opioid therapy until medical and neurologic factors have been fully evaluated.

Neuropathic pain may be less responsive to standard analgesics alone. Adjuvants such as antidepressants, anticonvulsants, benzodiazepines, local anesthetics, neuroleptics, psychostimulants, antihistamines, corticosteroids, levodopa, calcitonin, and diphosphonates are useful for particular indications (Table 8)[32,33]. These agents may be administered through oral and other routes [34].

Nonpharmacologic Treatment

Many nonpharmacologic approaches are available for the treatment of cancer pain, but the indications for these forms of therapy have yet to be defined.

Stimulation and Ablation: The loss of normal sensory input, as occurs when a peripheral nerve is severed, may lead to deafferentation pain. Some patients obtain relief from electrical stimulation, which augments non-nociceptive input (Table 9)[19]. Neurostimulation may be applied transcutaneously or via implanted devices to peripheral nerves, the spinal cord, or the brain. Carefully selected patients may benefit from surgical implantation of stimulation devices [35,36].

Neuroablation, or destruction of nerve tissue, may be accomplished by chemical or surgical means. The goal of this technique is to isolate the site of somatic pain from the central nervous system. The efficacy of each procedure must be weighed against the risks. A significant percentage of patients who fail to respond to oral therapy may be helped with appropriate nerve blocks. It is not known which patients might benefit from earlier procedures [37,38]. Somatic nerve blocks may be diagnostic (ie, to determine the indication for permanent neurolysis of somatic nerves), facilitative, prophylactic, or therapeutic. Visceral blocks (such as the celiac plexus block) have been demonstrated to be effective for specific pain syndromes. Sympathetically maintained pain is suggested when signs of marked sympathetic dysfunction accompany typical diffuse burning or deep aching pain. Sympathetic blockade may then be diagnostic and therapeutic. In some cases of refractory generalized pain, pituitary adenolysis has been effective (Table 10)[19].

Surgical ablation [39] may be accomplished by rhizotomy (section of nerve root) or dorsal root entry-zone lesions. Spinal anterolateral tractotomy or cordotomy, mesencephalotomy, medullary tractotomy, and cingulotomy should be reserved for carefully selected cases.

Physical Therapy: Physical therapy modalities, such as massage, ultrasonography, hydrotherapy, electroacupuncture, and trigger point injection, are indicated for musculoskeletal pain and may enhance exercise tolerance in a patient undergoing rehabilitation [40]. Skillful soft-tissue manipulation is probably underutilized.

Psychological Techniques: Cancer patients may regain a much needed sense of control by using psychological techniques, such as imagery, hypnosis, relaxation, biofeedback, and other cognitive-behavioral methods [41].

Ongoing Care

The goals of treatment must be frequently reviewed and integrated into the overall management plan [42,43]. Communication among the professional staff, patient, and family or other significant caregivers is essential. A sensitive, frank discussion with the patient regarding his or her wishes should guide medical decision-making during all phases of illness.

Conclusions

Control of cancer pain remains a challenge. A combination of pharmacologic and nonpharmacologic methods will relieve pain for the majority of cancer patients, yet a significant number of patients have pain that defies our best efforts to provide effective therapy. Current investigation into the pathophysiology of some forms of neuropathic pain holds promise for the development of new strategies. Advances in existing ambulatory-care technology may produce better systems for the long-term management of pain.

References:

References

1. Levin DN, Cleeland CS, Dar R: Public attitudes toward cancer pain. Cancer 56:2337–2339, 1985.

2. Portenoy RK: Cancer pain: Epidemiology and syndromes. Cancer 63:2298–2307, 1989.

3. World Health Organization: Cancer Pain Relief and Palliative Care. Geneva, World Health Organization, 1990.

4. Stjernsward J: Cancer pain relief: An important global public health issue, in Fields HL, et al (eds): Advances in Pain Research and Therapy, vol 9, pp 555–558. New York, Raven Press, 1985.

5. Bonica JJ: Treatment of cancer pain: Current status and future needs, in Fields HL, et al (eds): Advances in Pain Research and Therapy, vol 9, pp 589–616. New York, Raven Press, 1985.

6. American College of Physicians, Health and Public Policy Committee: Drug therapy for severe chronic pain in terminal illness. Ann Intern Med 99:870–873, 1983.

7. Ventafridda V, Tamburini M, Caraceni A, et al: A validation study of the WHO method for cancer pain relief. Cancer 59:850–856, 1987.

8. Walker VA, et al: Evaluation of WHO analgesic guidelines for cancer pain in a hospital-based palliative care unit. J Pain Symptom Management 3:145–149, 1988.

9. Breitbart W: Suicide, in Holland J, Rowland J (eds): Handbook of Psychooncology, pp 291–299. New York, Oxford University Press, 1990.

10. von Roenn JH, Cleeland CS, Gonin R, et al: Physician attitudes and practice in cancer pain management: A survey from the Eastern Cooperative Oncology Group. Ann Intern Med 119:121–126, 1993.

11. Hill CS, Fields HL (eds): Drug Treatment of Cancer Pain in a Drug-Oriented Society: Advances in Pain Research and Therapy, vol 11. New York, Raven Press, 1990.

12. Friedman D: Perspectives on the medical use of drugs of abuse. J Pain Symptom Management 5(suppl):S2–5, 1990.

13. Acute Pain Management Guideline Panel: Acute Pain Management: Operative or Medical Procedures and Trauma. Clinical Practice Guideline. AHCPR Publ No 92-0032. Rockville, Md, Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, 1992.

14. Portenoy RK, Payne R: Acute and Chronic Pain, in Lowinson JH, Ruiz P, Millman RB (eds): Substance Abuse: A Comprehensive Textbook, 2nd ed, pp 691–721. Baltimore, Williams & Wilkins, 1992.

15. NIH Consensus Development Conference Statement: The Integrated Approach to the Management of Pain, vol 6, no 3, 1986.

16. IASP Subcommittee on Taxonomy: Pain terms: A list with definitions and notes on usage. Pain 8:249–252, 1980.

17. Portenoy RK: Mechanisms of clinical pain: Observations and speculations. Neurol Clin 7:207, 1989.

18. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd ed, Revised, pp 264–267. Washington, DC, American Psychiatric Association, 1987.

19. Foley KM, Arbit E: Management of cancer pain, in DeVita VT, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology, vol 2, 3rd ed, pp 2064–2087. Philadelphia, JB Lippincott, 1989.

20. Twycross RG, Fairfield S: Pain in far-advanced cancer. Pain 14:303–310, 1982.

21. Colodney A, Weinstein, SM, Multidisciplinary management of cancer pain. Pain Digest 1:221–229, 1991.

22. McGrath PJ, Unruh AM: Pain in Children and Adolescents: The Measurement and Assessment of Pain. New York, Elsevier Science Publishers, 1987.

23. Deragotis LR, Marrow GR, Fetting J, et al: The prevalence of psychiatric disorders among cancer patients. JAMA 249:754, 1983.

24. Foley KM: Pharmacologic approaches to cancer pain management, in Fields HL et al (eds): Advances in Pain Research and Therapy, vol 9, pp 629–653. New York, Raven Press, 1985.

25. McGrath PA: Pain in Children: Nature, Assessment, and Treatment. New York, Guilford Press, 1990.

26. American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 3rd ed. Skokie, Illinois, American Pain Society, 1992.

27. Inturrisi C: Management of cancer pain-pharmacology and principles of management. Cancer 63(suppl):2308–2320, 1989.

28. Plummer J, Cherry D, Cousins M, et al: Long-term spinal administration of morphine in cancer and non-cancer pain: A retrospective study. Pain 44:215–220, 1991.

29. Greenberg HS: Continuous spinal opioid infusion for intractable cancer pain, in Foley KM, Inturrisi C (eds): Advances in Pain Research and Therapy, vol 8, pp 351–359. New York, Raven Press, 1986.

30. Jaffe JH: Drug addiction and drug abuse, in Gilman AG, Goodman LS, Rall TW, et al (eds): The Pharmacologic Basis of Therapeutics, 8th ed, pp 532–581. New York, Macmillan Publishing Co, 1985.

31. Porter J, Jick H: Addiction rare in patients treated with narcotics. N Engl J Med 302:123, 1980.

32. Bonica JJ: The Management of Pain. Philadelphia, Lea & Febiger, 1990.

33. Payne R, Foley KM (eds): Cancer pain. Med Clin North Am 71:2, 1987.

34. Portenoy RK: Pharmacologic Management of Neuropathic Pain; A Neurology Alert Special Report. American Health Consultants, 1992.

35. Meyerson BA: Electrostimulation procedures: Effects, presumed rationale, and possible mechanisms, in Bonica JJ, et al (eds): Advances in Pain Research and Therapy, vol 5; pp 495–534. New York, Raven Press, 1983.

36. Duncan GH, Bushnell MC, Marchand S: Deep brain stimulation: A review of basic research and clinical studies. Pain 45:49–60, 1991.

37. Arner S: The role of nerve blocks in the treatment of cancer pain. Acta Anaesthesiol Scand Suppl 74:104–108, 1982.

38. Cousins MJ, Bridenbaugh PO (eds): Neural Blockade, 2nd Ed. Philadelphia, JB Lippincott, 1988.

39. Meyerson BA: The role of neurosurgery in the treatment of cancer pain. Acta Anaesthesiol Scand Suppl 74:109–113, 1982.

40. Travell J, Simons D: Myofascial Pain and Dysfunction. Baltimore, Williams & Wilkins, 1983.

41. Breitbart W: Psychiatric management of cancer pain. Cancer 63(suppl):2336–2342, 1989.

42. Coyle N, Adelhardt J, Foley KM: Changing patterns in pain, drug use, and routes of administration in the advanced cancer patient. Pain (suppl 4):S339, 1987.

43. Twycross RG, Lack SA: Therapeutics in Terminal Cancer, 2nd ed. London, Churchill Livingstone, 1990.