Antinociceptive effects of mu- and kappa-agonists in inflammation are enhanced by a peripheral opioid receptor-specific mechanism.

Rats received an injection of Freund's complete adjuvant into the right hindpaw and developed localized inflammation. Four to six days after inoculation, the antinociceptive effect of both the mu-agonist, morphine, and the kappa-agonist U-50,488H, administered subcutaneously, was markedly enhanced in the inflamed paws. This effect was dose dependently antagonized by low dose of intraplantar, but not subcutaneous or intravenous, (-)-naloxone. (+)-Naloxone was inactive. These data indicate that the enhanced antinociceptive effects of both agonists in inflammation are mediated by a peripheral, opioid receptor-specific mechanism.