Evidence against the Participation of μ‐ and κ‐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 of ketorolac, of ketocyclazocine, the prototype κ‐agonist, and of morphine, the prototype μ‐agonist, were assayed in the pain‐induced functional impairment model in the rat. All three drugs induced a significant analgesic effect in this model. Naloxone was able to antagonize the effects of ketocyclazocine and morphine. However, the effect of ketorolac was not blocked by naloxone, although a high dose, 3·2 mg kg⁻¹, capable of blocking κ‐receptors was used. It is concluded that activation of μ‐ or κ‐opioid receptors, by either a direct or an indirect mechanism, does not play a role in the analgesic activity of ketorolac. 1995 Royal Pharmaceutical Society of Great Britain