Iwata Ken, Takamatsu Yukio, Doi Nagafumi, Ikeda Kazutaka
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Department of Neuropsychiatry, Tokyo Metropolitan Hiroo General Hospital, Tokyo, Japan.
Mol Pain. 2021 Jan-Dec;17:1744806921992628. doi: 10.1177/1744806921992628.
Electroconvulsive therapy (ECT) has been applied for chronic pain for decades. The amounts of opioids to treat pain are sometimes reduced after a series of ECT. The effect of ECT on morphine-induced analgesia and its mechanism underlying the reduction of morphine requirement has yet to be clarified. Therefore, we administered electroconvulsive shocks (ECS) to mice and investigated the antinociceptive effect of morphine in a hot plate test. We examined the expression level of µ-opioid receptor in the thalami of mice 25 h after administration of ECS compared to the thalami of mice without ECS administration using western blotting. ECS disturbed the development of a decrease in the percentage of maximal possible effect (%MPE), which was observed 24 h after a morphine injection, when ECS was applied 25, 23, 21, and 12 h before the second administration of morphine. We also examined the effect of ECS on the dose-response curve of %MPE to morphine-antinociception. Twenty-five hours after ECS, the dose-response curve was shifted to the left, and the EC of morphine given to ECS-pretreated mice decreased by 30.1% compared to the mice that were not pretreated with ECS. We also found that the expression level of µ-opioid receptors was significantly increased after ECS administration. These results confirm previous clinical reports showing that ECT decreased the required dose of opioids in neuropathic pain patients and suggest the hypothesis that this effect of ECT works through the thalamus.
几十年来，电休克疗法（ECT）一直被用于治疗慢性疼痛。经过一系列ECT治疗后，有时用于治疗疼痛的阿片类药物用量会减少。ECT对吗啡诱导的镇痛作用及其降低吗啡需求量的潜在机制尚待阐明。因此，我们对小鼠施加电休克（ECS），并在热板试验中研究吗啡的抗伤害感受作用。与未施加ECS的小鼠丘脑相比，我们使用蛋白质印迹法检测了施加ECS后25小时小鼠丘脑中μ-阿片受体的表达水平。当在第二次注射吗啡前25、23、21和12小时施加ECS时，ECS干扰了吗啡注射后24小时观察到的最大可能效应百分比（%MPE）下降的发展。我们还研究了ECS对%MPE吗啡镇痛剂量反应曲线的影响。ECS后25小时，剂量反应曲线向左移动，与未接受ECS预处理的小鼠相比，接受ECS预处理的小鼠给予吗啡的半数有效浓度（EC）降低了30.1%。我们还发现，施加ECS后μ-阿片受体的表达水平显著增加。这些结果证实了先前的临床报告表明ECT降低了神经性疼痛患者所需的阿片类药物剂量，并提出了ECT这种作用通过丘脑起作用的假说。
