Berkowitz B A, Finck A D, Ngai S H
J Pharmacol Exp Ther. 1977 Dec;203(3):539-47.
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.
本研究的目的是进一步描述氧化亚氮镇痛的性质，并确定是否会产生对氧化亚氮的耐受性。文中描述了研究气体镇痛作用的方法。在小鼠中，氧化亚氮在苯基醌和醋酸诱发的腹部收缩试验中具有镇痛作用。阿司匹林和非常高剂量的酒精在这些试验中也有活性；然而，只有氧化亚氮诱导的镇痛作用能被麻醉拮抗剂拮抗。这些数据表明氧化亚氮镇痛的作用机制与其他两种药物不同。通过甩尾法测定，氧化亚氮在大鼠中产生剂量相关的镇痛反应（半数有效量，67%）。5至30毫克/千克的纳洛酮也能拮抗大鼠的氧化亚氮镇痛作用。较低剂量的拮抗剂无效。长时间暴露后，大鼠和小鼠对氧化亚氮的作用均产生了耐受性。这些数据支持了氧化亚氮与阿片类药物具有显著药理学相似性的假说，并且最终可能在大脑中产生类似的分子事件从而减轻疼痛。
