Delta- and kappa-opioid agonists inhibit plasma extravasation induced by bradykinin in the knee joint of the rat.

We used an experimental model of neurogenic inflammation, plasma extravasation induced by bradykinin or capsaicin, to study the effect of receptor-selective opioid agonists on plasma extravasation. Plasma extravasation was induced in the knee joint of the rat by continuous perfusion of either bradykinin (160 ng/ml), an inflammatory mediator produced at sites of tissue injury, that produces plasma extravasation significantly dependent on the sympathetic postganglionic neuron, or capsaicin (5 mg/ml), a C-fiber excitotoxin, that induces plasma extravasation that is dependent on both primary afferents and sympathetic post-ganglionic neurons. When selective delta-((d-Pen2,5)-enkephalin) or kappa-(trans-3,4-dichloro-N-methyl-N[2-(- pyrolidinyl)cyclohexyl]benzeneacetamide; U50,488H) opioid agonists were perfused with bradykinin, plasma extravasation was significantly attenuated. Co-perfusion of the non-selective opioid antagonist naloxone (1 microM), reversed this opioid-induced inhibition of bradykinin-induced plasma extravasation. In contrast, co-perfusion of a selective mu-opioid agonist (Tyr-d-Ala-Gly-NMe-Phe-Gly-ol) did not reduce bradykinin-induced plasma extravasation. Tyr-d-Ala-Gly-NMe-Phe-Gly-ol was, however, able to completely inhibit the plasma extravasation produced by capsaicin. These results suggest that delta- and kappa-, but not mu-selective opioids inhibit bradykinin-stimulated plasma extravasation, while a mu-selective opioid inhibits primary afferent-dependent plasma extravasation. Therefore, inhibition of neurogenic plasma extravasation by receptor-selective opioids may depend on the relative contribution to plasma extravasation of unmyelinated afferent and sympathetic postganglionic neuron terminals. Our findings can also explain, in part, the variation in anti-inflammatory effects of receptor-selective opioids reported in different inflammatory conditions.