Nitrous oxide produces antinociceptive response via alpha(2B) and/or alpha(2C) adrenoceptor subtypes in mice

Background Opiate receptors in the periaqueductal gray region and alpha(2) adrenoceptors in the spinal cord of the rat mediate the antinociceptive pro perties of nitrous oxide (N2O). The availability of genetically altered mic e facilitates the detection of the precise protein species involved in the transduction pathway. In this study; the authors establish the similarity b etween rats and mice in the antinociceptive action of N2O and investigate w hich alpha(2) adrenoceptor subtypes mediate this response. Methods: After obtaining institutional approval, antinociceptive dose-respo nse and time-course to N2O was measured in wild-type and transgenic mice (D 79N), with a nonfunctional alpha(2A) adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemical ly with yohimbine (nonselective alpha(2) antagonist), naloxone (opiate anta gonist), L659,066 (peripheral alpha(2)-antagonist) and prazosin (alpha(2B)- and alpha(2C)- selective antagonist). The tail-flick latency to dexmedetom idine (D-med), a nonselective alpha(2) agonist, was tested in wild-type and transgenic mice. Results N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic m ice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinoci ceptive response could be dose dependently antagonized by opiate receptor a nd selective alpha(2B)-/alpha(2C)-receptor antagonists but not by a central nervous system-impermeant alpha(2) antagonist (L659,066). Whereas dexmedet omidine exhibited no antinociceptive response in the D73N mice, the robust antinociceptive response in the wild-type Lifter mates could not be blocked by a selective alpha(2B)-/alpha(2C)-receptor antagonist. Conclusion: These data confirm that the antinociceptive response to an exog enous alpha(2)-agonist is mediated by an alpha(2A) adrenoceptor and that th ere appears to be a role for the alpha(2B)- or alpha(2C)-adrenoceptor subty pes, or both, in the analgesic response to N2O.