Adrenalectomy potentiates the antinociceptive effects of calcium channel blockers.

Calcium channel blockers can modulate the nociceptive threshold. However, the underlying mechanism(s), especially the role of hypothalamic-pituitary-adrenal (HPA) axis, on this effect has not yet been clarified. In the present study we investigated the analgesic effect of verapamil, diltiazem and nimodipine in intact and adrenalectomized (ADX) male rats and also measured the effect of these drugs on HPA function. The tail-flick and hot-plate tests were used to assess the nociceptive threshold before and 15, 30, 60 and 120 min after drug administration. Corticosterone level was measured by radioimmunoassay as a marker of HPA function. Our results showed that these drugs could elicit antinociceptive effects which were more prominent in the hot-plate than in the tail-flick tests. Following the exclusion of adrenal glands these drugs showed stronger analgesic effects. Acute administration of verapamil, diltiazem and nimodipine produced significant decrease in plasma corticosterone level that was more prominent by nimodipine. In conclusion, the results of our study show that the HPA function has an important role in the antinociceptive effect of calcium channel blockers.