Antinociceptive effect of systemic kelatorphan, in mononeuropathic rats, involves different opioid receptor types.

The antinociceptive effect of i.v. kelatorphan (2.5, 5, 10 and 15 mg/kg), a mixed inhibitor of enkephalin degrading enzymes, was studied in a rat model of peripheral unilateral mononeuropathy (chronic constriction of the common sciatic nerve). Kelatorphan at 2.5 and 5 mg/kg had no significant effect on the vocalization threshold to paw pressure test, but higher doses (10 mg/kg) produced a significant antinociceptive effect which plateaued at 15 mg/kg, on both hindpaws. Kelatorphan (10 mg/kg) was co-injected with the specific mu-, delta- and kappa-opioid receptor antagonists naloxone (0.1 mg/kg), naltrindole (1 mg/kg) or nor-binaltorphimine (1 mg/kg). The effect of kelatorphan 10 mg/kg was completely prevented by naloxone, reduced by 75% by naltrindole (both hindpaws), and reduced by 50% by nor-binaltorphimine (contralateral paw only).