Effects of nimesulide on nitric oxide-induced hyperalgesia in humans—a neurophysiological study

• Published in: European journal of pharmacology Vol. 450; no. 3; pp. 259 - 262
• Main Authors: Sandrini, Giorgio, Tassorelli, Cristina, Cecchini, Alberto Proietti, Alfonsi, Enrico, Nappi, Giuseppe
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.2002; Elsevier
• Subjects: Adult; Analgesics; Analysis of Variance; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cross-Over Studies; Cyclo-oxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Double-Blind Method; Electric Stimulation; Female; Humans; Hyperalgesia - chemically induced; Hyperalgesia - physiopathology; Isoenzymes - metabolism; Male; Medical sciences; Membrane Proteins; Neuropharmacology; Nimesulide; Nitric oxide (NO); Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitroglycerin - pharmacology; Pain; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Reflex - drug effects; RIII threshold; Spinal Cord - drug effects; Spinal Cord - physiology; Sulfonamides - pharmacology; Vasodilator Agents - pharmacology; Pain; Nimesulide; RIII threshold; Nitric oxide (NO); Cyclo-oxygenase; Human; Nociception; Prostaglandin-endoperoxide synthase; Spinal cord; Healthy subject; Enzyme; Isozyme; Central nervous system; Oral administration; Flexion reflex; Hyperalgesia; Non steroidal antiinflammatory agent; Analgesic; Nitric oxide; Placebo; Antipyretic; Oxidoreductases; Mechanism of action; NMDA receptor; Comparative study
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02188-X

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.