Abstract

The antinociceptive effect of intraplantar (i.pl.) ICI 204448 (( R,S)- N-[2-( N-methyl-3,4-dichloro-phenylacetamido)-2-(3-carboxyphenyl)-ethyl]pyrrolidine hydrochloride)) (20, 30, 40 and 50 μg), a κ-opioid receptor agonist which has limited access to the central nervous system, was studied in a well-established rat model of peripheral mononeuropathy produced by moderate constriction of the sciatic nerve. Vocalization thresholds to paw pressure were used as a nociceptive test. On the injected nerve-injured paw, ICI 204448 at 20 and 30 μg had no significant effect, but higher doses (40 μg) produced a significant antinociceptive effect, which plateaued at 50 μg. By contrast, no antinociceptive effect was observed on the contralateral paw. The effect of ICI 204448 (40 μg) was significantly antagonised by the specific κ-opioid receptor antagonist nor-binaltorphimine (20 and 30 μg), when co-injected in the nerve-injured paw.

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