Effects of U-69,593, a κ-opioid receptor agonist, on carrageenin-induced peripheral oedema and Fos expression in the rat spinal cord

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In an attempt to study the anti-inflammatory and the antinociceptive effects of a κ 1-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 κ-opioid receptor specific since the anti-inflammatory effect of 1.5 mg/kg i.v. of U-69,593 was antagonised by a specific κ-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 κ-opioid receptor agonist are of minor importance for the antinociceptive effects of this compound.