Nitrous Oxide Produces Antinociceptive Response via α2B and/or α2C Adrenoceptor Subtypes in Mice


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Abstract

BackgroundOpiate receptors in the periaqueductal gray region and [small alpha, Greek]2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2 O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2 O and investigate which [small alpha, Greek]2 adrenoceptor subtypes mediate this response.MethodsAfter obtaining institutional approval, antinociceptive dose-response and time-course to N2 O was measured in wild-type and transgenic mice (D79N), with a nonfunctional [small alpha, Greek]2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2 O was tested after pretreatment systemically with yohimbine (nonselective [small alpha, Greek]2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral [small alpha, Greek]2-antagonist) and prazosin ([small alpha, Greek]2B- and [small alpha, Greek] (2C-selective) antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective [small alpha, Greek]2 agonist, was tested in wild-type and transgenic mice.ResultsN2 O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2 O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective [small alpha, Greek]2B-/[small alpha, Greek]2C-receptor antagonists but not by a central nervous system-impermeant [small alpha, Greek]2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective [small alpha, Greek]2B-/[small alpha, Greek]2C-receptor antagonist.ConclusionThese data confirm that the antinociceptive response to an exogenous [small alpha, Greek]2-agonist is mediated by an [small alpha, Greek]2A adrenoceptor and that there appears to be a role for the [small alpha, Greek]2B- or [small alpha, Greek]2C-adrenoceptor subtypes, or both, in the analgesic response to N2 O.

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