Antinociceptive activity of intrathecal ketorolac is blocked by the kappa-opioid receptor antagonist, nor-binaltorphimine.

Systemic and intrathecally administered ketorolac produced antinociception in the p-phenylquinone test, but not in the tail-flick or hot-plate tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathecally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketorolac and intrathecally administered ketorolac. Naloxone and ICI 174,864 failed to block the effects of ketorolac. Activation of nor-binaltorphimine-sensitive receptors appears to be an integral element in the mechanism of antinociception of ketorolac at the spinal level. Ketorolac did not precipitate withdrawal jumping in morphine-tolerant mice demonstrating that ketorolac does not act as a mixed agonist-antagonist at the opioid receptor. We suggest that neuraxial placement of ketorolac may prove useful in the clinical setting for the management of acute pain in humans.