Background. Opiate receptors in the periaqueductal gray region and α2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). 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 N2O and investigate which α2 adrenoceptor subtypes mediate this response. Methods: After obtaining institutional approval, antinociceptive dose-response and time- course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional α(2A) adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective α2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral α2-antagonist) and prazosin (α(2B)- and α(2C)- selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective α2 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 mice. Antinociception from N2O 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 α(2B)-/α(2C)-receptor antagonists but not by a central nervous system-impermeant α2 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 α(2B)-/α(2C)-receptor antagonist. Conclusion. These data confirm that the antinociceptive response to an exogenous α2-agonist is mediated by an α(2A) adrenoceptor and that there appears to be a role for the α(2B)- or α(2C)-adrenoceptor subtypes, or both, in the analgesic response to N2O.
- Opiate receptors
- Tail flick
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine