Evidence for the Involvement of Spinal Cord α1 Adrenoceptors in Nitrous Oxide-induced Antinociceptive Effects in Fischer Rats

Background: In a previous study, the authors found that nitrous oxide (N2O) exposure induces c-Fos (an immunohistochemical marker of neuronal activation) in spinal cord [gamma]-aminobutyric acid-mediated (GABAergic) neurons in Fischer rats. In this study, the authors sought evidence for the involvement of [alpha]1 adrenoceptors in the antinociceptive effect of N2O and in activation of GABAergic neurons in the spinal cord.

Methods: Adult male Fischer rats were injected intraperitoneally with [alpha]1 adrenoceptor antagonist, [alpha]2 adrenoceptor antagonist, opioid receptor antagonist, or serotonin receptor antagonist and, 15 min later, were exposed to either air (control) or 75% N2O. In some animals, nociception was investigated with the plantar test after 30 min of exposure, while in other animals, gas exposure was continued for 90 min and the spinal cord was examined for c-Fos immunostaining. In a separate experiment, animals were exposed to the above gases alone, after which the spinal cords were examined immunohistochemically for c-Fos and [alpha]1 adrenoceptor by double-staining methods.

Results: The antinociceptive effect of N2O was attenuated by prazosin (an [alpha]1 adrenoceptor antagonist), yohimbine (an [alpha]2 adrenoceptor antagonist), and naloxone (an opioid receptor antagonist) but not by methysergide and tropisetron (serotonin receptor antagonists). N2O exposure induced c-Fos expression in the spinal cord, which was blocked by prazosin and naloxone but not by other drugs. N2O-induced c-Fos expression was colocalized with [alpha]1 adrenoceptor immunoreactivity in laminae III-IV.