Spinal and supraspinal analgesic effects of Nimodipine : The role of Hypothalamo-Pituitary-Adrenal(HPA) axis .

Nimodipine, an L-type calcium channel blocker, can induce analgesia. However, it is not clear that this analgesic effect is at the level of spinal or supraspinal pain pathway. In addition, it has been reported that the analgesic effect of nifedipine, another L-type calcium channel blocker is related to the HPA axis, but there is no report indicating the role of this axis in the analgesic effect of nimodipine. Methods: Analgesia was measured by tail-flick (TF) test involving spinal reflexes and by hot-plate (HP) requiring an intact central nervous system. Assays were done before and 15, 30, 60 and 120 min after drug administration in the intact, sham operated and adrenalectomized rats. To identify the interaction between nimodipine and HPA axis, plasma corticosterone level was measured using the radioimmunoassay. Results: Nimodipine significantly decreased the plasma corticosterone level, and showed significant antinociception in both tests. Adrenalectomy potentiated the analgesic effect of nimodipine which was reversed by corticosterone replacement. Furthermore, nimodipine analgesic effect in ADX rats was more potent in HP test (compared to TF test). Nimodipine, at mentioned doses, did not alter animal’s movement indices in activity monitoring test. Conclusion: Nimodipine involves both spinal and supraspinal sites to control thermal pain transmission in presence of adrenal gland. It seems that there is a mutual interaction between nimodipine and HPA axis, especially at supraspinal levels.