Evidence for the involvement of spinal cord alpha1 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 alpha1 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 alpha1 adrenoceptor antagonist, alpha2 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 alpha1 adrenoceptor by double-staining methods.


RESULTS
The antinociceptive effect of N2O was attenuated by prazosin (an alpha1 adrenoceptor antagonist), yohimbine (an alpha2 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 alpha1 adrenoceptor immunoreactivity in laminae III-IV.


CONCLUSIONS
These findings support the hypothesis that N2O activates GABAergic interneurons through alpha1 adrenoceptors to produce its antinociceptive effect.
Orii
Ryo
R
Department of Anaesthetics and Intensive Care, Imperial College of Science, Technology and Medicine, University of London, 369 Fulham Road, London SW10 9NH, UK.
Ohashi
Yoko
Y
Guo
Tianzhi
T
Nelson
Laura E
LE
Hashimoto
Toshikazu
T
Maze
Mervyn
M
Fujinaga
Masahiko
M
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D008297:Male; D009609:Nitrous Oxide / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D016760:Proto-Oncogene Proteins c-fos; D011942:Receptors, Adrenergic, alpha; D009609:Nitrous Oxide