Opioid receptor types and antinociceptive activity in chronic inflammation: both kappa- and mu-opiate agonistic effects are enhanced in arthritic rats.

The antinociceptive effects obtained in arthritic rats with morphine, the opioid mu-agonist DAGO [D-Ala2,MePhe4,Gly-ol5]enkephalin, the delta-selective agonist DTLET [D-Thr2, Leu5]enkephalyl-Thr, and the kappa-agonist U-50,488H were compared to their corresponding effects in normal animals and morphine-pretreated arthritic rats, respectively, using a paw pressure test. The effects of the mu- and kappa-agonists were increased in arthritic rats. While morphine-treated rats were cross-tolerant to the mu- and kappa-agonists, no tolerance to the delta-selective agonist was found. The possibility that the potent action of morphine in this model for chronic inflammatory pain is mediated partly through kappa-mechanisms is discussed.