Nitrous oxide produced a concentration-related suppression of phenylquinone-induced abdominal constriction in mice. This analgesic effect was significantly reduced (but not abolished) by systemic pretreatment with (-)-naloxone or naltrexone but not (+)-naloxone. Systemic pretreatment with methylnaltrexone failed to appreciably influence nitrous oxide analgesia; however, methylnatrexone, administered centrally, significantly attenuated the drug effect. Furthermore, nitrous oxide analgesia was significantly reduced by MR-2266 (which is relatively selective for kappa-opioid receptors) but not by beta-funaltrexamine (which is selective for mu-opioid receptors) at the doses employed in this study. These findings suggest that nitrous oxide analgesia might involve an activation of kappa-opioid receptors in the central nervous system; however, a possible involvement of mu-opioid receptors is not absolutely precluded by this study.
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