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Chronic Nonmalignant Pain:


ABSTRACT: The complexities of chronic nonmalignant pain and the contributions of psychosocial and environmental factors require assessment and treatment strategies that may go far beyond the use of analgesics. The first step is to rule out serious underlying conditions; determine the chronicity, quality, location, and intensity of the pain; assess aggravating environmental factors; and evaluate the patient's level of functioning. The pharmacologic regimen may include oral or topical analgesics, antidepressants, muscle relaxants, nerve stabilizers, and/or opioids. A comprehensive plan includes alternative modalities, such as physical and occupational therapy, stress management, relaxation techniques, and the treatment of comorbid conditions, including anxiety, depression, and sleep disorders. The optimal opioid regimen consists of methadone or a sustained-release opioid combined with a short-acting opioid for breakthrough pain.

Chronic pain is a major public health problem.Although the need for improved pain management has been well documented, greater efforts are needed to increase awareness of the consequences of pain for patients' health and social and occupational functioning.1

As an example of the scope of the problem, in 1995, there were almost 15 million office visits for "mechanical" low back pain, the most common cause of disability in persons younger than 45 years and the third most common cause in those older than 45 years.2 Low back pain was the second most common reason for visiting a primary care physician and accounted for about 2.8% of office visits.2

There are at least 36 million disabled persons in the United States (about 14% of the population),3 approximately 75% of whom have chronic pain.4 Chronic pain accounts for about 21% of emergency department visits and 25% of annual missed work days.5

The diagnosis and treatment of chronic pain can be frustrating for clinicians and patients. Physicians have been criticized for both undertreatment and overtreatment (especially with opioids and surgical procedures). The issue is complex, because although guidelines exist for the management of acute pain and cancer pain, there are no widely accepted guidelines for the treatment of chronic nonmalignant pain. The traditional biomedical model is often irrelevant. The World Health Organization algorithm, which was established for treatment of chronic malignant pain, is not directly applicable to the management of chronic nonmalignant pain, especially if other treatment modalities-such as rehabilitation, adjunctive medications, and behavioral therapy-are not considered. The complexities of chronic nonmalignant pain and the contributions of psychosocial and environmental factors require assessment and treatment strategies that may go far beyond the use of analgesics.

The optimal treatment of chronic pain may involve pharmacologic, behavioral, physical, and psychological interventions. Because primary care clinicians are usually the first to see a patient at the onset of symptoms, they have the opportunity to play a significant role in preventing the pain from becoming chronic and in minimizing the negative consequences of chronic painand its treatment.

Jamison and colleagues6 investigated the barriers to implementation of a disease management program for chronic pain among primary care physicians. Physicians reported improved confidence in treating chronic pain after patients were categorized according to their level of disability from pain and guidelines and treatment algorithms were provided. Some clinicians may be reluctant to use algorithms, especially if they are complex or lengthy; however, algorithms are helpful in settings in which there is limited time for each patient.

In this article, we offer guidelines that will help facilitate care and optimize the treatment of chronic nonmalignant pain.


The International Association for the Study of Pain has defined pain as "an unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage."7 However, not all patients have a source of tissue damage, and pain can be perpetuated by many other factors. The biopsychosocial model was developed to illustrate the interaction of physical, psychological, and social factors in patients with chronic pain.8 The role of the clinician in this model is to help patients acquire coping skills and encourage them to participate actively in their own care and treatment outcomes. The focus of therapy is not on symptoms but on strategies that increase functional abilities despite the persistence of pain. Effective treatment of chronic pain also requires an understanding of how physical, psychological, and social factors affect the 4 key parameters of nociception, pain, suffering, and pain behavior (Figure).8,9

Nociception is the result of tis-sue damage caused by mechanical, chemical, or thermal energy; nociceptive information is transmitted to the CNS by finely myelinated A, delta, and unmyelinated C fibers.

Pain is the perception of a noxious stimulus that occurs when nociceptive information reaches the CNS. Acute pain is elicited by tissue injury and results from nociceptor activity at the site of tissue damage. However, pain may also occur in the absence of somatic pathology when there is damage to the nervous system that leads to altered input or CNS processing, as in phantom limb pain.

Suffering is a negative affective response generated in higher centers of the CNS by pain or other states such as fear, anxiety, or depression. Suffering usually leads to pain behaviors, which are positive or negative actions attributed to nociception. Patients with positive pain behavior may moan, cry, seek health care, or take medication. Patients with negative behavior may become isolated, inactive, or disabled.

Suffering behaviors and pain behaviors may appear virtually indistinguishable, but it is critical to make the distinction for an accurate evaluation of chronic pain. Patients who have the same kind of tissue injury may present differently, and the relationships between tissue injury, the report of pain, health care consumption, and loss of function are not fixed. A patient may manifest pain behaviors related to injury or in the absence of physical findings. Pain that extends beyond a reasonable period of healing in the absence of ongoing pathology is defined as chronic pain. Persons with chronic pain may present with behaviors that may easily be mislabeled as somatoform disorders. All pain is real; however, it is crucial to identify which of the 4 factors is most significant in the perpetuation of pain.

Pain may also be classified as somatic, visceral, or neuropathic:

•Somatic pain is usually well localized, sharp, or burning.

•Visceral pain is a diffuse, vague pain often referred to the body surface; it may be described as sickening.

•Neuropathic pain is burning or shooting pain that is usually precipitated by nerve injury or dysfunction from disease or trauma; it may also occur in CNS pathology in the absence of peripheral nociception.

Proper classification of pain aids in diagnosis, directs evaluation of the patient, and influences the choice of treatment options.


A thorough musculoskeletal and neurologic assessment is essential. At the initial visit, rule out serious medical conditions, reassure the patient that no such disorder is present, and address his or her concerns. Discuss the results of any imaging studies that have been performed. Determine the chronicity of the pain syndrome; the quality, location, and intensity of the pain; and aggravating environmental factors, such as work or marital problems or stress.

A numeric pain scale may be used to rate pain; however, some patients prefer a visual analog scale (VAS). Functional limitations both at work and at home must be addressed. The Short Form 36 (SF-36), the Roland disability questionnaire, or even a VAS can be used to determine activity levels. These scales can be used periodically (every 2 or 3 visits) to assess progress.

Determine what treatments the patient may have undergone and, if they failed, the reasons for the failure. For example, if the patient discontinued treatment, was this because of side effects, ineffectiveness, or lack of compliance? Was the patient engaged in a physical exercise program, and was it helpful? Were any alternative therapies tried?

Discuss the patient's goals and expectations and discourage any that are unrealistic. Educate the patient about chronic pain and emphasize the role of self-care. Be sure that the patient agrees with the plan and wishes to proceed.


The treatment of chronic pain requires communication and trust-building between patient and clinician, and the implementation of a long-term management plan. The goals of multidisciplinary pain management are listed in Table 1.

The successful use of medications for chronic pain depends on careful clinical reasoning founded on a working knowledge of the phenomenology and physiology of pain syndromes and the specific actions of these drugs, including their behavioral and cognitive effects.9 The principles of appropriate prescribing are listed in Table 2. Pharmacology in chronic pain management usually includes opioids and adjunctive drugs. Adjunctive drugs, such as antidepressants and anticonvulsants, can be very effective, especially in the treatment of neuropathic pain. Treatment options for neuropathic pain are listed in Table 3.10

Nonopioid pharmacologic options for chronic pain include:


•Muscle relaxants.

•Nerve stabilizers (such as gabapentin, oxcarbazepine, topiramate, zonisamide, and lamotrigine).

•Tricyclic antidepressants (TCAs) (such as amitriptyline, nortriptyline, and doxepin).

•Serotonin/norepinephrine reuptake inhibitors (such as venlafaxine).

•Topical agents (such as a 5% lidocaine patch, capsaicin cream, and lidocaine/prilocaine cream).

•α2-Antagonists (such as clonidine and tizanidine).

Antidepressants with both serotonin and norepinephrine reuptake inhibition, such as venlafaxine, show the greatest analgesic effect.11 Tricyclic and tetracyclic antidepressants can moderately relieve chronic back pain; selective serotonin reuptake inhibitors (SSRIs) do not.12 The antidepressant trazodone is also an effective sleeping agent.

Because of the superior effectiveness of antidepressants with mixed mechanisms of action (such as venlafaxine) and the well-documented benefits of TCAs in the management of chronic pain, these agentsmay be tried first. SSRIs are reserved for patients who do not respond to or cannot tolerate TCAs.13

Although the number of randomized controlled studies of biofeedback and relaxation training is limited, these modalities are cost- effective, relatively benign, and effective for chronic pain. Acupuncture appears to help patients with pain syndromes, especially those with musculoskeletal pain. Transcutaneous electrical nerve stimulation is helpful in acute pain; its role in chronic pain is less well defined.14 Therapeutic exercise and physical rehabilitation (including physical and occupational therapy) have important roles in treating chronic pain and maximizing function. Modalities such as ultrasonography, cryotherapy, hot compresses, and ice packs can be helpful in the initial stages of physical rehabilitation.

If a patient has radiating symptoms (shooting pain to lower or upper limbs), an epidural corticosteroid injection may provide relief and help facilitate rehabilitation. Patients with degenerative arthritis of the spine who experience focal back pain may benefit from trigger point or facet joint injections. Patients with complex regional pain syndrome (CRPS) are best referred to a pain specialist for sympathetic nerve blocks at the onset of the disease. Early intervention in CRPS prevents disease progression and is more effective than late intervention. Patients who do not respond to sympathetic nerve blocks and pharmacologic treatment may be referred to an interventionalist for a trial of a spinal cord stimulator.

Patients who continue to have symptoms after trials of oral and topical medications may wish to consider a trial of an intrathecal opioid. If this is successful, a pump and catheter can be implanted to deliver the opioid.


Although these agents are often used in chronic pain management, clinicians may be uncomfortable prescribing them. They may be apprehensive about potential lack of efficacy, creating addiction, or managing possible side effects. A paucity of clinical guidelines and concern about potential legal and regulatory ramifications add to the discomfort. Nevertheless, a consensus has emerged that opioid therapy can relieve pain and improve mood and functioning in many patients who have chronic nonmalignant pain, and consensus statements have been developed to guide prescribing practices.15 Standard agents and dosages are listed in Table 4.

A range of aberrant drug-taking behaviors may occur in patients who are undergoing opioid therapy for chronic pain. It is important to assess and understand these kinds of behaviors and their relationship to addiction. Red flags include frequent requests for escalating doses of opioids and the use of opioids to treat other symptoms (such as anxiety, depression, or sleep disorders). Other warning signs are repeated instances of "lost prescriptions," forging prescriptions or selling prescription drugs, and altering the drug delivery system or route of administration. A history of alcohol or substance abuse indicates an increased risk of addiction.

In patients who have an addiction problem, optimal medical management of chronic pain involves careful ongoing assessment, a strict opioid agreement, prudent drug selection, and frequent follow-up visits (including the use of urine toxicology screening).16

It is important to establish agreed-on goals for treatment and follow-up. Be sure the patient understands the difference between dependence, tolerance, and addiction:

•Addiction is a disease process involving use of psychoactive substances characterized by loss of control and continued compulsive use despite adverse social, physical, psychological, or spiritual consequences.

•Pseudoaddiction refers to apparent drug-seeking behaviors that result from undertreatment of pain.

•Tolerance is the state in which an increased dosage of a drug is needed to produce the same desired effect.

•Physical dependence is a physiologic state of adaptation to a specific substance characterized by the emergence of a withdrawal syndrome during abstinence, which may be relieved in total or in part by readministration of the substance. Physical dependence is not a synonym for addiction.

•Psychological dependence is a subjective sense of need for a specific substance, either for its positive effects or to avoid negative effects associated with its absence.

Addiction is rare in patients with chronic pain.17 Failure to establish good pain relief is a much more common problem. Drug-seeking behavior often results from disease or undertreatment, not addiction.

An opioid agreement is an effective way to link specialty and primary care services in the delivery of chronic opioid therapy.18 This agreement usually consists of consent to initiate opioid therapy and an affirmation by the patient that he will receive opioids from one physician only and will use the medication exactly as prescribed. The agreement allows the physician to use random urine drug screening and, in cases of suspected abuse, to discontinue therapy. If the treatment is ineffective or the patient has side effects, or if the patient misuses the drug, the physician may discontinue opioid treatment. If a patient breaks the agreement, the physician has the right to stop treating him. In any of these scenarios, the opioid should be tapered gradually before discontinuation.

Collaboration with a pain specialist is recommended when long-term opioid therapy is instituted. The specialist should be included in the opioid agreement process, particularly during and after the transition from specialty to primary care.18 Consultation with a specialist is also recommended if the primary care physician is unsure of which medications to prescribe, what the starting dose should be, and how to up-titrate the dose; or if interventional therapy, such as a nerve block, epidural corticosteroid injection, or diagnostic blocks, is indicated.

The optimal opioid regimen consists of methadone or a sustained-release opioid combined with a short-acting opioid for breakthrough pain.Methadone is started at a low dose that is not increased more than once a week because the half-life is unpredictable. Use caution when switching from methadone to another opioid or vice versa, because there is a wide range of equivalencies. For example, one dose of methadone is not equivalent to one dose of morphine. Consultation with a pain specialist is warranted in this situation.

Limit the number of short-acting opioid tablets. Use only one sustained-release and one short-acting opioid. Adjunctive medications, such as TCAs or nerve stabilizers, may be added. Periodically assess compliance, efficacy, and side effects. Monitor for signs of opioid abuse, such as a request for early refills, losing or mishandling prescriptions, or asking for a specific opioid. Any suspicious activities should be discussed with the patient. If a drug is ineffective, taper and discontinue it. If the first opioid tried is only partially effective, increase the dose of a sustained-release opioid within certain limits, according to the goals set up at the initiation of therapy. If the medication is effective, but the patient has side effects such as constipation or nausea and vomiting, these can be managed with stool softeners, increased fiber consumption, and antiemetic agents.

Discuss with the patient possible long-term effects of opioids, such as tolerance, dependence, and endocrine abnormalities. If tolerance develops, switching to another opioid may be helpful. There is usually only partial cross-tolerance between opioids.

Some types of pain are not opioid-sensitive. In this setting, the dose of opioid should not be increased. The best approach is to gradually taper and discontinue the opioid. A trial of another opioid or adjunctive agent can be considered in this situation.


Patients with complex chronic pain often become resistant to conventional as well as alternative therapies or do not show functional improvement. Referral to a comprehensive multidisciplinary pain center is indicated in these circumstances, although it would be better to anticipate the need for such a referral before chronic pain becomes thoroughly entrenched. Evidence suggests that multidisciplinary treatment is highly effective for nonmalignant chronic pain.19 Aside from relieving pain, treatment reduces the use of opioids and health care services; it increases activity and the return-to-work rate and facilitates the closing of disability claims. In several randomized trials, a cognitive-behavioral self-care program for back pain resulted in a greater reduction in pain ratings and interference with activities than did conventional care.14,20,21

If there is no multidisciplinary pain center in the area, the role of the primary care physician is to coordinate and implement patient care. This may involve consulting with a psychologist to treat comorbid conditions, such as depression, anxiety, or sleep disorders, and with a physical therapist to implement an exercise program. The focus of these efforts is on function and activity, rather than pain. Encourage the patient to play a role in self-care and suggest the use of alternative therapies, such as acupuncture, biofeedback, relaxation training, and stress management. n



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16. Passik SD. Pain clinicians' rankings of aberrant drug-taking behaviors. J Pain Palliat Care Pharmacother. 2002;16:39-49.

17. Christo PJ. Opioid effectiveness, addiction, and depression in chronic pain. Adv Psychosom Med. 2004;25:123-137.

18. Mahajan G, Fishman S. Opioid contracts and primary care physicians. Pain Med. 2002;3:183.

19. Loeser JD, Turk DC. Multidisciplinary pain management. In: Loeser JD, ed. Bonica's Management of Pain. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2001:2069-2079.

20. Moore JE. A randomized trial of a cognitive- behavioral program for enhancing back pain self-care in a primary care setting. Pain. 2000;88: 145-153.

21.Moffett JK. Randomized controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences. BMJ. 1999;319:279-283.

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