Nitrous oxide analgesia: reversal by naloxone and development of tolerance

The objective of this study was to characterize further the nature of nitrous oxide analgesia and to establish if tolerance to nitrous oxide occurs. Methods for studying the analgesic action of a gas are described. In mice, nitrous oxide is analgesic in the phenylquinone and acetic acid abdominal constriction tests. Aspirin and very high doses of alcohol are also active in these tests; however, only nitrous oxide-induced analgesia is antagonized by narcotic antagonists. These data indicate the mechanism of action of nitrous oxide analgesia differs from that of the other two drugs. Nitrous oxide produced a dose-related analgesic response in rats (ED50, 67%) as measured by the tail-flick method. Naloxone, 5 to 30 mg/kg, also antagonized nitrous oxide analgesia in rats. Lower doses of the antagonist were not effective. Tolerance developed to the effects of nitrous oxide in both rats and mice after prolonged exposure. These data lend support to the hypothesis that nitrous oxide and opiates have a significant pharmacologic resemblance and may ultimately produce similar molecular events in the brain leading to the relief of pain.