Nifedipine potentiates antinociceptive effects of morphine in rats by decreasing hypothalamic pituitary adrenal axis activity

It has been shown that nifedipine, as a calcium channel blocker can potentiate the antinociceptive effect of morphine; however, the role of Hypothalamic-Pituitary-Adrenal (HPA) axis on this action has not been elucidated. We examined the effect of nifedipine on morphine-induced analgesia in intact and adrenalectomized (ADX) rats and on HPA activity induced by morphine. To determine the effect of nifedipine on morphine analgesia, nifedipine (2 mg/kg i.p.) that had no antinociceptive effect, was injected concomitant with sub-effective dose of morphine (1 and 2 mg/kg). The tail-flick test was used to assess the nociceptive threshold, before and 15, 30, 60, 90, 120 and 180 min after drug administration. Our results showed that, nifedipine could potentiate the antinociceptive effect of morphine and this effect of nifedipine in ADX was greater than sham operated rats which, was reversed by corticosterone replacement. Nifedipine has an inhibitory effect on morphine -induced corticosterone secretion. Thus, the data indicate that the mechanism underlying the potentiation of morphine analgesia by nifedipine involves mediation, at least in part, by attenuating the effect of morphine on HPA axis.