N-methyl-D-aspartate receptor-mediated chronic pain: New approaches to fibromyalgia syndrome etiology and therapy

Objectives: Fibromyalgia syndrome [FMS], a poorly understood form of chronic pain, is under-diagnosed and under-treated. It is possible that stress-induced disturbances of endocrine and neurological systems underlie the ultimate expression of FMS. One of these systems, involving the N-Methyl-D-Aspartate [NMDA] receptor, is implicated in FMS as it is in other chronic pain conditions. Therefore, the objective of this review is to provide evidence for targeting the NMDA receptor for FMS pharmacotherapy and discuss its significance to FMS pain. Findings: Major barriers to effective management of FMS pain are the fact that there are no discrete objectifiable physical findings, psychological stress is often thought to be the sole explanation, and the pathophysiology of FMS pain remains unclear. Yet, an impressive body of evidence suggests that FMS pain is likely due to central sensitization. Given its role in central pain perception and processing, the NMDA receptor represents a possible lynchpin in the pathogenesis of chronic pain in FMS. Conclusions: We propose that the very centrality of NMDA receptors in chronic pain makes them an ideal target for pharmacotherapy in FMS. Reports of recent clinical trials using newer low-affinity NMDA receptor antagonists have shown analgesic affects in chronic pain states other than FMS. These new compounds represent novel avenues of research into the management of chronic pain.