Contralateral, ipsilateral and bilateral treatments with the kappa-opioid receptor agonist U-50,488H in mononeuropathic rats

Abstract

The effect of repeated contralateral administration of the kappa-opioid receptor agonist U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate) on nociceptive behaviour was investigated and compared with ipsilateral and bilateral treatments in a rat model of peripheral unilateral neuropathy (chronic constriction of the common sciatic nerve). Administration of 0.3 mg U-50,488H into the contralateral hindpaw on days 6 and 10 after induction of mononeuropathy increased hindpaw withdrawal latency to mechanical but not to thermal stimulation compared to saline-treated rats. No difference in pain-related behaviour was found between different peripheral (contralateral, ipsilateral and bilateral) treatments with 0.3 mg U-50,488H. Autotomy behaviour was reduced for 6 weeks after sciatic nerve ligation in rats treated contralaterally with the opioid receptor agonist. Antinociceptive effects of contralaterally administered U-50,488H were abolished by the peripherally acting opioid receptor antagonist naloxone methiodide. Our findings indicate that contralateral treatment with U-50,488H attenuates nociceptive behaviour in mononeuropathic rats. These antinociceptive effects are mediated via peripheral opioid receptors.