Koyama T, Mayahara T, Wakamatsu T, Sora I, Fukuda K
Department of Anaesthesia, Kyoto University Hospital, Kyoto, Japan.
Br J Anaesth. 2009 Nov;103(5):744-9. doi: 10.1093/bja/aep246. Epub 2009 Sep 18.
The role of the endogenous opioid system in the anaesthetic effect of volatile anaesthetics and the analgesic action of nitrous oxide (N2O) is unclear. In the current study, we investigated whether the mu-opioid receptor (MOP) is involved in these activities using MOP knockout (MOP-KO) and wild-type (WT) mice.
Minimum alveolar concentrations (MACs) for sevoflurane, isoflurane, and halothane, and the sevoflurane MAC-sparing effect of N2O were determined in homozygous MOP-KO and WT mice. The analgesic effect of N2O and the suppressive effect of naloxone on N2O analgesia were assessed in a writhing test and a hot-plate test. Immunohistochemical staining was used to visualize N2O-induced c-Fos expression in the lumbar spinal cord.
There were no significant differences in the MAC values of the three volatile anaesthetics or in the sevoflurane MAC-sparing effect of N2O 70% between MOP-KO and WT mice. There was also no significant difference in the analgesic effect of N2O 70% or in the level of c-Fos expression induced by N2O 70% between the two genotypes. In the writhing test, naloxone significantly attenuated N2O analgesia in MOP-KO and WT mice.
These results suggest that MOP is not required for the anaesthetic action of volatile anaesthetics and the analgesic effect of N2O. Opioid receptors other than MOP may mediate the analgesic action of N2O.
内源性阿片系统在挥发性麻醉药的麻醉作用及氧化亚氮（N2O）的镇痛作用中所起的作用尚不清楚。在本研究中，我们使用μ-阿片受体基因敲除（MOP-KO）小鼠和野生型（WT）小鼠，研究了μ-阿片受体（MOP）是否参与这些活动。
测定了纯合MOP-KO小鼠和WT小鼠对七氟烷、异氟烷和氟烷的最低肺泡有效浓度（MAC），以及N2O对七氟烷MAC的节省效应。在扭体试验和热板试验中评估了N2O的镇痛作用以及纳洛酮对N2O镇痛的抑制作用。采用免疫组织化学染色观察N2O诱导的腰段脊髓c-Fos表达。
MOP-KO小鼠和WT小鼠对三种挥发性麻醉药的MAC值或70%N2O对七氟烷MAC的节省效应均无显著差异。两种基因型小鼠对70%N2O的镇痛作用或70%N2O诱导的c-Fos表达水平也无显著差异。在扭体试验中，纳洛酮显著减弱了MOP-KO小鼠和WT小鼠的N2O镇痛作用。
这些结果表明，挥发性麻醉药的麻醉作用和N2O的镇痛作用并不需要MOP。除MOP外的其他阿片受体可能介导N2O的镇痛作用。
