A comparative study of the antinociceptive action of xenon and nitrous oxide in rats

We attempted to clarify the mechanism of antinociceptive action induced by xenon and nitrous oxide. Eighty percent of nitrous oxide or 80% xenon was applied to rats inside enclosed clear plastic glass cylinders with their tails protruding for assessment of the tail-flick response to radiant heat. With repeated testing, there was a rapid reduction to nitrous oxide antinociception within 90 min, which was interpreted as development of tolerance, but not to xenon antinociception. Nitrous oxide antinociception was blocked by the intraperitoneal administration of 0.1 or 1.0 mg/kg yohimbine, but not by 1.0 or 5.0 mg/kg L659-066 or by 5.0 or 10 mg/kg naloxone. Xenon antinociception was not affected by any of these drugs. Yohimbine and L659-066 are characterized as alpha 2-adrenoceptor antagonists. Although yohimbine penetrates the blood-brain barrier after systemic administration, L659-066 does not penetrate it and act peripherally. Therefore, the results indicate that alpha 2-adrenoceptors, but not opioid receptors, may play a key role in antinociception induced by nitrous oxide in the central nervous system. Furthermore, the mechanism of xenon antinociception differs from that of nitrous oxide because it does not involve either alpha 2 or opioid receptors.

The precise mechanism of antinociceptive action of nitrous oxide and xenon remains unknown. It is still controversial whether an opioid system plays a role in antinociception induced by nitrous oxide. The results of the study showed that antagonism of central alpha 2-adrenoceptors, but not opioid receptors, reverses the antinociception induced by nitrous oxide but not by xenon, which indicates that alpha 2-adrenoceptors may play a key role in nitrous oxide antinociception.