Potentiation of antihyperalgesic activity of diclofenac by nimodipine in a formalin model of facial pain in rats.

The present study evaluates the possible role of dihydropyridine calcium channel antagonist nimodipine on diclofenac analgesia in formalin-induced facial pain model in rats. Adult Wistar rats of either sex received an injection of 50 microl of 5% v/v subcutaneous formalin into one vibrissal pad and consequent facial grooming behaviour was monitored. Animals exhibited two distinct periods of nocifensive grooming: i) an acute phase lasting 0-6 min; and ii) a tonic phase lasting 6-45 min. The individual analgesic response of nimodipine and diclofenac was noted at doses of 5, 10 and 20 mg/kg i.p. and 1, 2 and 4 mg/kg i.p., respectively, administered 5 min prior to formalin injection. Diclofenac 1, 2 and 4 mg/kg i.p. produced dose-dependent inhibition of facial grooming in both acute and tonic phases. Nimodipine per se had antihyperalgesic effect, but to a very small extent. Nimodipine 10 and 20 mg/kg significantly potentiated the subanalgesic dose of diclofenac, i.e., 0.2 mg/kg. Results of the study showed that low dose nimodipine per se has insignificant antihyperalgesic effect. However, it potentiated the subanalgesic dose of diclofenac showing a synergistic response. These results imply that nimodipine can be used as an adjunct to the treatment of various neuropathic pains, postherpetic and diabetic neuropathies but the clinical efficacy needs to be evaluated in patients.