Involvement of hypothalamic pituitary adrenal axis on the nifedipine-induced antinociception and tolerance in rats

Nifedipine, a calcium channel blocker, can modulate the nociceptive threshold. However, the underlying mechanism, especially the role of HPA axis, on this effect has still not been elucidated. In the present study we investigated the analgesic effect of nifedipine in intact and adrenalectomized (ADX) male rats and we also measured the effect of nifedipine on HPA function. The Tail-Flick test was used to assess the nociceptive threshold before and 15, 30, 60, 90, and 120 min after drug administration. Corticosterone level was measured by radioimmunoassay as a marker of HPA function. Our results showed that in intact and sham operated animals, administration of 10 mg/kg nifedipine induces an antinociceptive effect. But at the dosage of 2 and 5 mg/kg animals do not exhibit this effect. With repeated injections, its analgesic effect was decreased, a phenomenon prevented by adrenalectomy. Acute administration of nifedipine produced significant decrease in plasma corticosterone level. In ADX animals, had a potent antinociceptive effect nifedipine at high dosage (10 mg/kg) as well as at lower dosage (5 mg/kg) that reversed with corticosterone replacement. In conclusion, the results of our study show that the elimination of HPA function through adrenalectomy potentiates the antinociceptive effect of nifedipine and attenuates its analgesic tolerance. Both effects are reversed by corticosterone replacement.