Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 484, Issue 2-3, Pages 193-199Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2003.11.021
Keywords
rofecoxib; nitric oxide (NO); cyclooxygenase
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The antinociceptive effect of rofecoxib, a preferential inhibitor of cyclooxygenase-2, was assessed in the pain-induced functional impairment model in the rat. Systemic administration of rofecoxib generated a dose-dependent antinociceptive effect in rats injected with uric acid into the knee joint of the right hindlimb in order to produce nociception. Ipsilateral intra-articular pretreatment with N-G-L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO) synthesis), 1H-(1,2,4)-oxadiazolo (4,2-a)quinoxalin-1-one (ODQ, an inhibitor soluble guanylyl cyclase), and the ATP-sensitive potassium channel blocker glibenclamide reversed the antinociceptive effect of rofecoxib p.o. However, ipsilateral intra-articular pretreatment with L-arginine (a NO substrate), or 3-morpholino-sydnonimine-HCl (SIN-1, a nonenzymatic donor of NO), potentiated the antinociceptive effect induced by rofecoxib. The present results suggest that, in addition to cyclooxygenase-2 inhibition, the antinociceptive effect of rofecoxib could also involve activation of the L-arginine-NO-cyclic GMP (cGMP) pathway, followed by opening of ATP-sensitive K+ channels at the peripheral level. (C) 2003 Elsevier B.V All rights reserved.
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