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 effect s of a kappa(1)-opioid receptor agonist (U-69,593: trans-3,4-dichloro-N-met hyl-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 int raplantar injection of carrageenin-induced the development of a peripheral oedema, associated with an increase in Fos-like immunoreactivity at the lev el of the dorsal horn of the spinal cord. U-69,593 administered intravenous ly (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-dependen t 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 w ere 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 recepto r antagonist nor-binaltorphimine. Pre-treatment with U-69,593 strongly decr eased 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 eff ects of this compound. (C) 1999 Elsevier Science B.V. All rights reserved.