Effects of nimesulide on nitric oxide-induced hyperalgesia in humans--a neurophysiological study.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce analgesia mainly via the inhibition of cyclo-oxygenase. Several reports suggest that chronic pain is mediated by central sensitization, an N-methyl-D-aspartate (NMDA)-mediated phenomenon influenced by cyclo-oxygenase activity and nitric oxide (NO). In this double-blind study, we evaluated the effects of a preferential inhibitor of the inducible isoform of cyclo-oxygenase-2, nimesulide, on the spinal nociceptive flexion reflex (RIII reflex) before and after administration of an NO donor in healthy volunteers. Nimesulide caused a reduction of the RIII reflex area, which persisted after NO donor administration. Conversely, in the placebo group the RIII reflex area significantly increased following the administration of the NO donor. These data suggest a central effect for nimesulide, possibly related to a reduction of nociceptive activity at spinal level.
Psychophysiology of Pain Laboratory, University Center for Adaptive Disorders and Headache, University of Pavia, Via Palestro 3, 27100 Pavia, Italy.
Giorgio
G
Sandrini
Cristina
C
Tassorelli
Alberto Proietti
AP
Cecchini
Enrico
E
Alfonsi
Giuseppe
G
Nappi
D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D013449:Sulfonamides; D014665:Vasodilator Agents; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005996:Nitroglycerin; C012655:nimesulide