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ANALGESIA

Dopamine D₂-Like Receptor in the Nucleus Accumbens Is Involved in the Antinociceptive Effect of Nitrous Oxide

Sahoko Koyanagi, MD^*, Shugaku Himukashi, MD^*, Kumiko Mukaida, MD^*, Tsutomu Shichino, MD, and Kazuhiko Fukuda, MD^*

From the *Department of Anesthesia, Kyoto University Hospital, and National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

Address correspondence and reprint requests to Dr. Sahoko Koyanagi, Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Address e-mail to sahoko{at}kuhp.kyoto-u.ac.jp.

Abstract

BACKGROUND: The mechanism of the antinociceptive effects of nitrous oxide (N₂O) has not been completely elucidated. On the other hand, numerous studies have indicated that mesolimbic dopaminergic neurons, which are thought to be involved in rewarding and reinforcement processes, play important roles in the supraspinal pain-suppression system. We hypothesized that the mesolimbic dopaminergic system is involved in the antinociceptive effect of N₂O.

METHODS: Adult male Fischer rats were used in this study. To examine whether the dopaminergic system is activated by N₂O, frozen sections of the ventral tegmental area of rats exposed to 75% N₂O were double-stained for c-Fos and tyrosine hydroxylase. To clarify whether the dopaminergic system is involved in the antinociceptive action of N₂O, saline or raclopride, a dopamine D₂-like receptor antagonist, was injected into the nucleus accumbens (NAc) shell region. After exposure to 25% oxygen–75% nitrogen or 25% oxygen–75% N₂O for 30 min, rats were subjected to formalin test, and the spinal cord was examined immunohistochemically.

RESULTS: Exposure to 75% N₂O increased c-Fos expression in tyrosine hydroxylase-positive cells in the ventral tegmental area. Raclopride, injected into the NAc shell region, attenuated the antinociceptive effect of N₂O in the formalin test, and blocked the suppressive effect of N₂O on the formalin-induced c-Fos expression in the dorsal horn of the spinal cord by N₂O.

CONCLUSION: It is possible that inhalation of N₂O activates mesolimbic dopaminergic neurons, and that the antinociceptive effect of N₂O is at least partially mediated by dopamine D₂-like receptors in the NAc shell region.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999