ANTINOCICEPTIVE EFFECT OF A KAPPA-OPIOID RECEPTOR AGONIST THAT MINIMALLY CROSSES THE BLOOD-BRAIN-BARRIER (ICI-204448) IN A RAT MODEL OF MONONEUROPATHY

The antinociceptive effect of intraplantar (i.pl.) ICI 204448 ylacetam ido)-2-(3-carboxyphenyl)-ethyl]pyrrolidine hydrochloride)) (20, 30, 40 and 50 mu g), a kappa-opioid receptor agonist which has limited acces s 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 use d as a nociceptive test. On the injected nerve-injured paw, ICI 204448 at 20 and 30 mu g had no significant effect, but higher doses (40 mu g) produced a significant antinociceptive effect, which plateaued at 5 0 mu g. By contrast, no antinociceptive effect was observed on the con tralateral paw. The effect of ICI 204448 (40 mu g) was significantly a ntagonised by the specific kappa-opioid receptor antagonist nor-binalt orphimine (20 and 30 mu g), when co-injected in the nerve-injured paw.