Blockade of the antinociceptive activity of centrally administered ketorolac by nor-binaltorphimine

Abstract

Antinociceptive activity of intracerebroventricularly administered ketorolac tromethamine was evaluated in mice by measuring inhibition of abdominal stretching induced by p-phenylquinone. Ketorolac tromethamine produced dose-dependent antinociception with an ED 50 of 7.34 μg/mouse (4.97–10.82) and a maximal effect at 30 μg. Selective antagonists of opioid receptors were used to determine ketorolac's mechanism of action. The ketorolac tromethamine-induced antinociception was not blocked by the μ- and δ-opioid receptor antagonists, naloxone and ICI-174,864 ( N,N-diallyl-Tyr-Aib-Aib-Phe-Leu), respectively; however, the κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride significantly blocked this effect. These findings suggest that activation of κ-opioid receptors appears to play a role in the mechanism of the antinociceptive effect of ketorolac tromethamine. Ketorolac tromethamine may induce the release of endogenous κ-opioids to produce central nervous system antinociception.