Nifedipine potentiates the antinociceptive effect of endomorphin-1 microinjected into the periaqueductal gray in rats

Endomorphin-1 is a novel endogenous μ-opioid ligand. We investigated the antinociceptive interaction between endomorphin-1 and nifedipine, an L-type calcium channel blocker, microinjected into the midbrain ventrolateral periaqueductal gray (vPAG), using the spinally-organized tail-flick test and the supraspinally-organized tail-pressure test in rats. Sprague-Dawley rats were stereotaxically implanted with a guide cannula lowered into the vPAG. Microinjection of endomorphin-1 into the vPAG led to dose-related increases in antinociceptive responses in the tail-flick test and tail-pressure test. Pretreatment with the μ-opioid receptor-selective antagonist β-funaltrexamine blocked the antinociceptive effect of endomorphin-1. Pretreatment with β-funaltrexamine alone had no effect on the tail-flick latency and tail-pressure threshold. Microinjection of nifedipine alone into the vPAG did not produce an antinociceptive response in the tail-flick test and tail-pressure test. However, injection of nifedipine into the vPAG potentiated the antinociceptive effect of endomorphin-1, producing a significant leftward shift in the dose-response curve of endomorphin-1 in both the tail-flick and tail-pressure tests. This result shows that the potent antinociceptive effect of endomorphin-1 microinjected into the vPAG is mediated through the μ-opioid receptor and is potentiated by concomitant administration of nifedipine.