title: Delta- and kappa-opioid agonists inhibit plasma extravasation induced by bradykinin in the knee joint of the rat.
abstract: 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.
authors.affiliation: Department of Anatomy, University of California, San Francisco 94143-0452A.
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology*; D007596:Joints / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*
chemical_list: D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D002211:Capsaicin; D001920:Bradykinin