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REGIONAL ANESTHESIA AND PAIN MEDICINE

Antinociceptive Action of Epidural K+_ATP Channel Openers via Interaction with Morphine and an ₂- Adrenergic Agonist in Rats

Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Gifu City, Japan

Address correspondence to Shuji Dohi, MD, Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, 40 Tsukasamachi, Gifu City, Gifu 500-8705, Japan. Address e-mail to shu-dohi{at}cc.gifu-u.ac.jp

Potassium (K⁺) channels may play some role in the analgesic actions of µ-opioid agonists and ₂-adrenergic agonists (₂ agonists). We examined whether the adenosine triphosphate-sensitive K⁺(K⁺_ATP) channel openers, levcromakalim and nicorandil, (given epidurally), might have antinociceptive effects in a tail flick test in adult male Sprague-Dawley rats implanted with a lumbar epidural catheter. The interactions with morphine and an ₂ agonist were also examined. The epidural administration of levcromakalim (10 µg, 100 µg) or nicorandil (10 µg, 100 µg) alone did not produce antinociception, but 100 µg levcromakalim or nicorandil did potentiate the antinociceptive effect induced by epidural morphine. Epidural glibenclamide (10 µg), a K⁺_ATP channel blocker, or naloxone (10 µg) antagonized this potentiation. Systemic administration of levcromakalim or nicorandil (at the same dose as that given into the epidural space) did not potentiate the epidural morphine-induced analgesia. A combination of epidural dexmedetomidine (1 µg) and morphine (1 µg) (each at a subantinociceptive dose) had a significant antinociceptive effect, and epidural glibenclamide (10 µg) partly antagonized this antinociception. These data suggest that levcromakalim and nicorandil potentiate the analgesic action of both morphine and dexmedetomidine, probably via an activation of K⁺_ATP channels at the spinal cord level.

Implications: Epidural administration of adenosine triphosphate-sensitive potassium channel openers potentiated the analgesic actions of morphine and an ₂-adrenergic agonist, presumably via activation of adenosine triphosphate-sensitive potassium channels at the spinal cord level.

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				K. Niinomi, Y. Banno, H. Iida, and S. Dohi Nicorandil, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Inhibits Muscarinic Acetylcholine Receptor-Mediated Activation of Extracellular Signal-Regulated Kinases in PC12 Cells Anesth. Analg., December 1, 2008; 107(6): 1892 - 1898. [Abstract] [Full Text] [PDF]