EVIDENCE AGAINST THE PARTICIPATION OF MU-OPIOID AND KAPPA-OPIOID RECEPTORS IN THE ANALGESIC ACTIVITY OF KETOROLAC IN RATS

The possibility that activation of opioid receptors is involved in the analgesic activity of ketorolac was explored. The analgesic effects o f ketorolac, of ketocyclazocine, the prototype kappa-agonist, and of m orphine, the prototype mu-agonist, were assayed in the pain-induced fu nctional impairment model in the rat. All three drugs induced a signif icant analgesic effect in this model. Naloxone was able to antagonize the effects of ketocyclazocine and morphine. However, the effect of ke torolac was not blocked by naloxone, although a high dose, 3.2 mg kg(- 1), capable of blocking kappa-receptors was used. It is concluded that activation of mu- or kappa-opioid receptors, by either a direct or an indirect mechanism, does not play a role in the analgesic activity of ketorolac.