Effects of the N-Methyl-D-Aspartate Receptor on Temporal Summation of Second Pain (Wind-up) in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the pathophysiological mechanisms of the pain and hypersensitivity are not well understood. IBS patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting that central hyperalgesic mechanisms may be involved. In the current study, during the wind-up testing session, a series of 6 heat pulses were presented with an interstimulus interval (ISI) of 3 seconds. Following the 1st, 3rd, and 6th thermal stimuli, subjects were asked to rate the late thermal sensation or second pain. IBS patients who demonstrated temporal summation of pain (TSSP) then received dextromethorphan and placebo in a randomized, double-blind, fashion to block wind-up. The results showed: 1) a subset of IBS patients, but not controls, showed TSSP in response to a series of noxious heat pulses; and 2) TSSP was blocked by administration of dextromethorphan, an NMDA receptor antagonist. In summary, these findings further elucidate mechanisms of somatic hypersensitivity in a subset of IBS patients. Our results also support an etiologic basis for abnormal NMDA receptor mechanisms in some IBS patients. Future studies are needed to determine if NMDA receptor antagonists may be used to treat IBS patients. Perspective: This study evaluates temporal summation of second pain in a subset of IBS patients that is blocked by Dextromethorphan, an NMDA receptor antagonist. Theses results could lead to the use of an NMDA receptor antagonist in the treatment of pain in a subset of IBS patients.