L-ARGININE-NO SYSTEM PARTICIPATES IN THE ANALGESIC EFFECT OF FLUNIXIN MEGLUMINE IN THE RAT

This study investigated whether the L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 mu g) into the rat's hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a significant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was significantly increased in comparison with the effect of FM alone. L-arginine (L-ARG; 10 mg/kg; i.p.) itself did not produce signifi cant effect on carrageenan-induced hyperalgesia, but signifi cantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.