A Role for Inflammation in Chronic Pain

Curr Rev Pain. 1999;3(6):440-446. doi: 10.1007/s11916-999-0071-4.


Recent studies indicate that inflammatory events induced by nerve injury play a central role in the pathogenesis of neuropathic pain. These involve inflammatory cells (eg, macrophages), the production of molecules that mediate inflammation (cytokines/interleukins), and the production of nerve growth factor (NGF). However, in many instances, neuropathic pain is associated with nerve inflammation, neuritis, in the absence of nerve injury. Studies on the role of cytokines in neuropathic pain have only recently begun, mostly in model systems that involve nerve injury. Little is known about the role of inflammation in neuropathic pain in the absence of nerve injury. We developed an animal model to study neuropathic pain and underlying inflammatory mechanisms in a system in which neuropathic pain is induced by nerve inflammation in the absence of injury, neuritis. Neuritis is provoked by local application of complete Freund's adjuvant (CFA) on the sciatic nerve. The following events in the course of experimental neuritis are described: 1) the time course of neuropathic pain, 2) the structural changes in axons and myelin, and 3) the spontaneous electrical activity (peripheral sensitization). It is conceivable that biochemical and physiologic changes (inflammatory mediators) that occur along the "pain pathway" (nociceptors, peripheral nerve, dorsal root ganglion ), dorsal root, neurons in the spinal cord) may sensitize one or all these sites along the pain pathway and hence lead to chronic pain).