Effects of U-69,593, a kappa-opioid receptor agonist, on carrageenin-induced peripheral oedema and Fos expression in the rat spinal cord.
In an attempt to study the anti-inflammatory and the antinociceptive effects of a kappa1-opioid receptor agonist (U-69,593: trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)cycloexil]benzene acetamide methanesulfonate), we used a combination of the measurement of peripheral oedema (with a calliper) and Fos immunodetection in the carrageenin model of inflammation. The intraplantar injection of carrageenin-induced the development of a peripheral oedema, associated with an increase in Fos-like immunoreactivity at the level of the dorsal horn of the spinal cord. U-69,593 administered intravenously (i.v.) 10 min before carrageenin administration over the dose range 0.75, 1.5 and 3 mg/kg, reduced both paw and ankle oedema in a non dose-dependent manner. The maximal decrease was observed at the highest dose and did not exceed 21% and 20% for the paw and the ankle respectively. These effects were kappa-opioid receptor specific since the anti-inflammatory effect of 1.5 mg/kg i.v. of U-69,593 was antagonised by a specific kappa-opioid receptor antagonist nor-binaltorphimine. Pre-treatment with U-69,593 strongly decreased the number of Fos-like Immunoreactive neurones of the spinal cord in a dose-dependent, antagonist reversible manner; maximal effect was 65%. The disparate results between the anti-inflammatory effects and the depressive effects on Fos expression suggest that anti-inflammatory effects of kappa-opioid receptor agonist are of minor importance for the antinociceptive effects of this compound.
Catheline
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Unité de Recherche de Physiopharmacologie du Système Nerveux, I.N.S.E.R.M. U 161 and E.P.H.E., Paris, France. cathel@broca.inserm.fr
Le Guen
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Besson
J M
JM
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D044482:Benzeneacetamides; D002351:Carrageenan / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced; D007120:Immunochemistry; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010784:Photomicrography; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D002351:Carrageenan; C045444:U 69593