EFFECT OF CAFFEINE COADMINISTRATION AND OF NITRIC-OXIDE SYNTHESIS INHIBITION ON THE ANTINOCICEPTIVE ACTION OF KETOROLAC

The effects of caffeine and nitric oxide synthesis inhibition on the a ntinociceptive action of ketorolac were assessed using the pain-induce d functional impairment model in the rat. Nociception was induced by t he intra-articular injection of uric acid. Ketorolac, but not caffeine , produced an antinociceptive effect which was reduced by NG-nitro-L-a rginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. I.-NAME i nduced a dose-dependent reduction of this potentiation. The results su ggest the participation of the L-arginine-nitric oxide-cyclic GMP path way in the caffeine potentiation of ketorolac-induced antinociception.