Fukuhara N, Ishikawa T, Kinoshita H, Xiong L, Nakanishi O
Department of Anaesthesiology-Resuscitology, Yamaguchi University School of Medicine, Japan.
Can J Anaesth. 1998 Nov;45(11):1123-9. doi: 10.1007/BF03012404.
Although several studies have demonstrated that both supra opiate receptors and spinal alpha 2 adrenoceptors play a mediating role in nitrous oxide(N2O) analgesia, controversy still exists. The present study was undertaken to evaluate further the involvement of noradrenergic (NA) neuronal activity in N2O analgesia by investigating tail-flick latency and supra- and spinal NA levels in rats.
In an analgesia study, effect of N2O 75% and its modification were evaluated using the tail-flick test in male Wistar rats. Results were expressed as % maximum possible effect (MPE). Modification of N2O analgesia was examined in rats pretreated with either the alpha 2 receptor agonist, clonidine(CLO: 150 micrograms.kg-1, i.p.), alpha 2 receptor antagonist, idazoxone(IDZ: 100 micrograms.kg-1, i.v.) by lesioning the locus coeruleus (LC) seven days before exposure to N2O, or naloxone (5 mg.kg-1, i.v.). Also, in a NAergic neuronal transmission study, the changes in NA content at LC and spinal cord were determined using HPLC-ECD.
Nitrous oxide produced analgesia, % MPE increased to a maximum of 78% at 30 min, thereafter declining to 38% at 120 min. Clonidine potentiated the analgesic effect of N2O at 120 min (80%). The analgesic effect of N2O was attenuated by IDZ or by LC lesioning. However, naloxone, in a dose sufficient to block morphine-induced analgesia, had no effect. With N2O exposure, NA content was decreased by 52% in the LC and by 20% at spinal cord. With morphine, NA content did not differ from the control group.
The data suggest that N2O-induced analgesia is principally mediated by activation of the descending inhibitory NAergic system and/or increased NA release at spinal cord which may lead to presynaptic inhibition of primary afferent neurotransmitter release and hyperpolarize the dorsal horn neurons by alpha 2 receptors.
尽管多项研究表明，阿片受体和脊髓α2肾上腺素能受体在氧化亚氮（N2O）镇痛中均起介导作用，但仍存在争议。本研究旨在通过研究大鼠的甩尾潜伏期以及脑桥蓝斑核和脊髓中去甲肾上腺素（NA）水平，进一步评估去甲肾上腺素能（NA）神经元活动在N2O镇痛中的作用。
在一项镇痛研究中，使用甩尾试验评估75%氧化亚氮及其改良剂对雄性Wistar大鼠的作用。结果以最大可能效应（MPE）的百分比表示。在暴露于N2O前7天损毁脑桥蓝斑核（LC）、用α2受体激动剂可乐定（CLO：150μg·kg-1，腹腔注射）、α2受体拮抗剂咪唑克生（IDZ：100μg·kg-1，静脉注射）或纳洛酮（5mg·kg-1，静脉注射）预处理的大鼠中，检测N2O镇痛的改变。此外，在一项去甲肾上腺素能神经元传递研究中，使用高效液相色谱-电化学检测法（HPLC-ECD）测定LC和脊髓中NA含量的变化。
氧化亚氮产生镇痛作用，MPE百分比在30分钟时最高增加到78%，此后在120分钟时降至38%。可乐定在120分钟时增强了N2O的镇痛作用（80%）。IDZ或损毁LC减弱了N2O的镇痛作用。然而，足以阻断吗啡诱导镇痛的剂量的纳洛酮没有作用。暴露于N2O时，LC中的NA含量降低了52%，脊髓中的NA含量降低了20%。使用吗啡时，NA含量与对照组无差异。
数据表明，N2O诱导的镇痛主要通过下行抑制性去甲肾上腺素能系统的激活和/或脊髓中NA释放增加介导，这可能导致初级传入神经递质释放的突触前抑制，并通过α2受体使背角神经元超极化。
