DIFFERENTIAL EFFECT OF SELECTIVE CYCLOOXYGENASE-2 (COX-2) INHIBITOR NS-398 AND DICLOFENAC ON FORMALIN-INDUCED NOCICEPTION IN THE RAT

Prostaglandins (PGs) are known to be involved in inflammatory and noci ceptive processing. Since the discovery of at least two isozymes of cy clooxygenase (COX), inhibition of COX-2 has been suggested to be respo nsible for the therapeutic effects of nonsteroidal anti-inflammatory d rugs (NSAIDs). In the present study, the effects of a rather selective COX-2 inhibitor, NS-398 (0.3-27 mg/kg i.p.), were studied using the r at formalin test as a model of acute nociception. Diclofenac (non-sele ctive COX inhibitor; 0.3-27 mg/kg i.p.) was used as a control. NS-398 revealed antinociceptive activity only at a dose (27 mg/kg) which resu lts in plasma concentrations which most likely do not selectively inhi bit COX-2. By contrast, diclofenac inhibited formalin-induced flinchin g behaviour over the whole dose range tested. Our results suggest that PGs mediating nociception in the formalin test of the rat are most li kely produced via the COX-1 as well as COX-2 pathways. Thus, in an acu te model of nociception a nonselective COX inhibitor may offer advanta ges as compared to a selective COX-2 inhibitor. (C) 1998 Elsevier Scie nce Ireland Ltd.