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PAIN MEDICINE

Nifedipine Potentiates the Antinociceptive Effect of Endomorphin-1 Microinjected into the Periaqueductal Gray in Rats

Shuanglin Hao, MD PhD^*,, Keiko Mamiya, MD^*, Osamu Takahata, MD PhD^*, Hiroshi Iwasaki, MD PhD^*, Marina Mata, MD, and David J. Fink, MD

*Department of Anesthesiology & Critical Care Medicine, Asahikawa Medical College, Asahikawa, Japan; and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania

Address correspondence and reprint requests to Shuanglin Hao, MD, PhD, Department of Neurology, University of Pittsburgh Medical Center, S-522, BST, Pittsburgh, PA 15213. Address e-mail to haoshuanglin{at}hotmail.com

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 ß-funaltrexamine blocked the antinociceptive effect of endomorphin-1. Pretreatment with ß-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.

IMPLICATIONS: This study shows that the potent antinociceptive effect of endomorphin-1 microinjected into the ventrolateral periaqueductal gray is potentiated by concomitant administration of nifedipine. This suggests that calcium channel blockers may enhance the analgesia of opioids in patients with calcium channel blocker treatment.

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