The Pitfalls of Opioids for Chronic Nonmalignant Pain of Central Origin

Stephen G. Gelfand, MD


February 25, 2002

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.[13,14,15]

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.


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