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Cognizant Communication Corporation

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Nitrous oxide (N2O) is an anesthetic gas known to produce an analgesic effect at sub-anesthetic concentrations. This analgesic property of N2O can be clinically exploited in a broad range of conditions where pain relief is indicated. The mechanism of this analgesic effect was long thought to be nonspecific in nature, but a landmark study by Berkowitz and others in 1976 first implicated an opioid mechanism of action, possibly via N2O-stimulated neuronal release of endogenous opioid peptides to activate opioid receptors. N2O-induced release of opioid peptide has been demonstrated in both in vivo and in vitro preparations. Reversal of N2O-induced antinociception in animals by narcotic antagonists has been reported by a number of laboratories. Subsequent studies have utilized more selective opioid antagonists to identify the opioid receptor subtypes involved in the antinociceptive effect of N2O. Extensive pharmacological testing in the mouse abdominal constriction and rat hot plate paradigms have established that N2O-induced antinociception is mediated by κ-opioid receptors in the former and by µ- and -opioid receptors in the latter. Current studies focus on two recent developments. The poor responsiveness of the DBA/2J mouse strain to N2O has led to pharmacogenetic studies that hope to identify the underlying genetic basis for antinociceptive responsiveness to N2O. Other research suggests an involvement of nitric oxide (NO) in mediating the antinociceptive effects of N2O in both rats and mice.


Published version. Analgesia, Vol. 1, No. 3 (1995): 151-159. DOI. © 1995 Cognizant Communication Corporation. Used with permission.

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