More MS news articles for Mar 2002

The Pitfalls of Opioids for Chronic Nonmalignant Pain of Central Origin

Medscape Rheumatology 4(1), 2002
Stephen G. Gelfand, MD


A serious medical and social problem today is under intense media, law enforcement, and regulatory scrutiny: the misuse and abuse of OxyContin (oxycodone) for chronic nonmalignant pain. This situation has made the drug difficult to obtain for many patients with malignant and other types of intractable chronic pain, and has recently influenced the US Food and Drug Administration to issue a black box warning to lessen the chance of inappropriate prescribing of this Schedule II narcotic.[1]

In addition to recent Drug Enforcement Agency (DEA) autopsy findings of nearly 300 OxyContin overdose deaths nationally since January 2000,[2] a large volume of patients with chronic nonmalignant pain have become dependent or addicted as a result of legitimate prescriptions written for OxyContin, as well as other opioids.

In a recent case,[2] the DEA suspended physician narcotic licenses and closed a South Carolina pain clinic for the excessive prescribing of OxyContin, although the physicians involved believed they were following current established standards.

How did this situation occur? In the first place, certain statements in the narcotic guidelines established by the Federation of State of Medical Boards[3] have received insufficient or cursory attention. These include the recommendations on the importance of psychological and substance abuse evaluations, the necessity for other treatments depending on the etiology of the pain and extent of psychosocial impairment, and the requirement for consultation with or referral to an expert for comorbid psychiatric disorders.

These are common omissions, particularly in rural environments, where the OxyContin problem first originated, and in which psychosocial factors receive less attention, resulting in fewer numbers of referrals to mental health providers. Even before OxyContin came on the market, however, another opioid, hydrocodone, was one of the most widely abused drugs, particularly in rural areas of the South.[4]

Clearly, the large volume of prescriptions and chronic use of OxyContin have increased the supply, availability, and opportunities for every type of abuse, while also filtering into our schools.[5] Contributing to this situation has been an attempt to expand the indications for opioid therapy to the entire spectrum of chronic pain, regardless of cause.

As a result of an organized educational and marketing campaign by the manufacturer of OxyContin and a number of pain societies, the message has spread that pain is often undertreated in general and that opioids are safe in most instances and should be prescribed more often for chronic pain of all types.[6,7] If restricted to patients with cancer or other forms of intractable peripheral pathology, the use of opioids would be more acceptable, but the message also was intended and has been used to justify opioid treatment for many patients with nonmalignant, nonstructural chronic pain.

Because chronic widespread pain and psychological distress in the general population are closely associated,[8] the indications for treatment with opioids have been expanded to patients with chronic pain of central affective origin, including those within the wide spectrum of fibromyalgia, one of the most common rheumatic disorders.

Thus, the indications for opioid therapy have been extended to this large, heterogeneous group closely associated with a wide range of psychological distress, including the affective spectrum disorders.[9] These vulnerable patients are especially at risk for the dangers of opioid therapy, especially in rural regions where insufficient attention is given to pain-generating and amplifying psychosocial factors, in lieu of a more patient-popular drug-oriented approach.

The current "pain revolution" has also broadened the use of opioid drugs for chronic pain by focusing on quantitative criteria such as degrees of pain (a largely subjective parameter), rather than on etiology. However, the degree of pain often correlates poorly with objective findings, and quantitative factors have different levels of significance for the types of chronic pain common to different specialties, eg, oncology compared with rheumatology. This broad approach does not account for the essential distinctions in the biological and psychological origins of chronic pain subgroups, which are important to understand in making informed therapeutic decisions.

Furthermore, the appeal to broaden the indications for opioids has also trivialized possible long-term adverse consequences, particularly of OxyContin.[6,7] Consequently, as cited above, a number of pain clinics have formed for the primary reason of prescribing analgesics, especially opioids, while at the same time frequently downplaying or disregarding nonpharmacologic approaches, including psychological testing and management necessary for a large number of the chronic pain population.

Thus, the combined effect of expanding the indications for opioid use and insufficient attention to guideline recommendations has facilitated the current environment of OxyContin abuse, which has grown into a major medical, social, and law enforcement problem in many rural areas, as well as in an increasing number of metropolitan regions throughout the country.

In the last several years, OxyContin abuse has spread and reached epidemic proportions. The extent of this situation, which often involves generally law-abiding citizens, was recently reported in special television broadcasts on both CBS News' 48 Hours (in a segment entitled "Addicted") and MTV's "True Life: I'm Hooked on OxyContin." Susan Zirinsky, executive producer of the 48 Hours segment, which aired on December 12, 2001, states that "the growing addiction to prescription painkillers is a story that is touching every age group, and its effects are often devastating."[10]

Effects of Opioids on Chronic Nonmalignant Pain

Pain is a complex sensation modulated by central brain pathways, including the nerve centers and networks responsible for emotions. The types of chronic pain for which opioids were originally intended are caused by pathological processes in tissues or organs from diseases such as cancer or intractable nerve or joint damage. In these conditions, the drugs combine with opioid receptors on nerve cell bodies in the brain and spinal cord that connect to and attenuate the electrical activity of these afferent nerve pathways stimulated by peripheral tissue lesions.

In other common types of chronic pain, similar structural abnormalities in peripheral tissues are not present; instead, pain is produced and intensified by central brain mechanisms, including emotions, which are stimulated by a spectrum of chronic psychological distress and result in disordered central pain regulation and amplification.[11]

This latter type of chronic pain includes the fibromyalgia syndrome, in which symptoms have neurophysiological correlates originating from persistent central nervous system activation caused by a large range and high degree of stressful psychosocial life events.[12] The outcome is a persistent chronic stress response characterized by dysfunctional neuroendocrine reactivity to psychological, as well as to physical and physiological, stressors.[13-15]

Because opioids may have mood-elevating or altering effects, particularly in individuals with chronic pain and psychic distress (conscious or subconscious), these drugs may facilitate psychological dependence by their action on central affective nerve networks, as opposed to the peripheral afferent nerve pathways of tissue damage or destruction in patients with malignant pain. In essence, it appears that opioids work on different nerve pathways in fibromyalgia than they do in cancer, intractable nerve damage, or end-stage arthritis. This central action may also occur in vulnerable patients with nonstructural low back pain and tension headache.

The localization of opiates in the pleasure centers of the human brain and the recent demonstration of mu opioid receptors in the amygdala of nonhuman primates,[16] a brain region essential for emotional content and behavior, is further evidence of the intimate relationship between emotional states and pain processing.

The treatment of pain of central origin should focus on attenuating the causative and perpetuating psychobiological factors, rather than masking them with exogenous opioids. The risk of long-term dependency or addiction by their direct effects on the emotional component of pain while depleting the brain's natural endogenous opioids should make opioids a last resort for treatment of chronic, nonmalignant pain.

Even in conditions of chronic pain associated with peripheral pathology, such as the synovial inflammation or cartilage destruction of arthritis, central pain-modulating mechanisms may play an important role, a fact that has definite therapeutic implications. For instance, the recognition and management of underlying psychological disorders in patients with rheumatic diseases can significantly improve pain levels and function.[17] Self-management programs including education, exercise, and behavioral-cognitive therapies have likewise resulted in positive benefits beyond that of drug therapy alone.[18,19] Furthermore, dependence on painkillers, including opioids, may directly inhibit the learning of self-efficacy, which allows patients to take control and significantly reduce their own pain and other symptoms.[20] Unfortunately, for too many today, "taking a pill is easier than building the necessary will," a socio-cultural reality contributing to our national problem of prescription drug abuse, including that of OxyContin.

Effects of Opioid Dependence

Self-efficacy and dependence on drugs for pain are opposite therapeutic objectives. Although certain medications such as low-dose tricyclic antidepressants for improved sleep and selective serotonin reuptake inhibitors (SSRIs) for depression and/or persistent pain are beneficial in selected patients with fibromyalgia, conventional drug management by itself has not been shown to improve outcomes in this disorder.[21,22] The same conclusion also applies to chronic low back pain not caused by specific structural lesions. Both conditions frequently have multiple psychosocial and cognitive variables unique to each individual that need to be recognized and treated as part of a multidisciplinary treatment program including self-management techniques. Disregarding these factors, which are essential in the origin and amplification of symptoms, predisposes the patient to polypharmacy, drug dependence, and a dysfunctional state in which each symptom is medicalized.

One of the most common reasons for patient visits today is the large range and severity of multiple unexplained symptoms, including pain, which are associated with stressful life events, psychological distress, depression, and anxiety disorders.[23] Fibromyalgia syndrome should be viewed and managed in this broader context, rather than as a discrete disease requiring medications (including opioids) as principal therapy. Recognition that a number of these patients would rather have a "physical disease" than confront the effects of stressful past or present life circumstances may be helpful in their overall evaluation process. Furthermore, this comprehensive approach considers the chronic muscle pain of fibromyalgia syndrome to be just one of many symptoms that can be generated by chronic tension and stress originating from biopsychosocial factors, rather than as a distinct disease in the traditional biomedical sense.[12]


The lessons of OxyContin could serve to strengthen the importance of good clinical judgment and the need to evaluate each patient in context. This includes determining whether chronic pain originates from peripheral or central mechanisms, and adhering to the narcotic guidelines for adequate psychosocial evaluation prior to prescribing opioids.

Pain should not be treated in isolation without understanding of its roots, just as fever mandates a search for causes. Undertreatment should refer not only to drug therapy, but also to the absence of important nondrug interventions. The appropriate management of chronic pain is multimodal, including nonpharmacologic therapies, especially for pain of central origin. Diagnosis and care should be individualized and involve other disciplines as indicated, including clinical psychology, psychiatry, stress management, health education, and physical and/or occupational therapy.

As a result of the OxyContin problem, certain pain societies are now calling for a more balanced approach to the diagnosis and management of chronic pain.[24] It is likely that the aftermath of OxyContin will show that a "one drug fits all" orientation to chronic pain is a risky practice with many pitfalls. In the public interest, more attention must be paid to proper patient selection rather than to marketing ploys intended to increase drug sales.


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