Sodium leak channels in the central amygdala modulate the analgesic potency of volatile anaesthetics in mice

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

British journal of anaesthesia Pub Date : 2024-09-24 DOI:10.1016/j.bja.2024.06.049

Yaoxin Yang , Jingxuan Qiu , Jin Liu , Donghang Zhang , Mengchan Ou , Han Huang , Peng Liang , Tao Zhu , Cheng Zhou

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引用次数: 0

Abstract

Background

Analgesia is an important effect of volatile anaesthetics, for which the spinal cord is a critical neural target. However, how supraspinal mechanisms modulate analgesic potency of volatile anaesthetics is not clear. We investigated the contribution of the central amygdala (CeA) to the analgesic effects of isoflurane and sevoflurane.

Methods

Analgesic potencies of volatile anaesthetics were tested during optogenetic and chemogenetic inhibition of CeA neurones. In vivo calcium imaging was used to measure neuronal activities of CeA neuronal subtypes under volatile anaesthesia. Contributions of the sodium leak channel (NALCN) in GABAergic CeA (CeA^GABA) neurones to analgesic effects of volatile anaesthetics were explored by specific NALCN knockdown. Electrophysiological recordings on acute brain slices were applied to measure volatile anaesthetic modulation of CeA neuronal activity by NALCN.

Results

Optogenetic or chemogenetic silencing CeA neurones reduced the analgesic effects of isoflurane or sevoflurane in vivo. The calcium signals of CeA^GABA neurones increased during exposure to isoflurane or sevoflurane at analgesic concentrations. Knockdown of NALCN in CeA^GABA neurones attenuated antinociceptive effects of isoflurane, sevoflurane, or both. For example, mean concentrations of isoflurane, sevoflurane, or both that induced immobility to tail-flick stimuli were significantly increased (isoflurane: 1.17 [0.05] vol% vs 1.24 [0.04] vol%, P=0.01; sevoflurane: 2.65 [0.07] vol% vs 2.81 [0.07] vol%; P<0.001). In brain slices, isoflurane, sevoflurane, or both at clinical concentrations increased NALCN-mediated holding currents and conductance in CeA^GABA neurones, which increased excitability of CeA^GABA neurones in an NALCN-dependent manner.

Conclusions

The analgesic potencies of volatile anaesthetics are partially mediated by modulation of NALCN in CeA^GABA neurones.

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杏仁核中枢钠泄漏通道可调节小鼠体内挥发性麻醉剂的镇痛效力。

背景镇痛是挥发性麻醉剂的一个重要作用，而脊髓是其关键的神经靶点。然而，脊髓上机制如何调节挥发性麻醉剂的镇痛效力尚不清楚。我们研究了中央杏仁核（CeA）对异氟烷和七氟烷镇痛作用的贡献。方法在光遗传和化学遗传抑制 CeA 神经元的过程中测试挥发性麻醉剂的镇痛效力。体内钙成像用于测量挥发性麻醉下 CeA 神经元亚型的神经元活动。通过特定的 NALCN 敲除，探讨了 GABA 能 CeA（CeAGABA）神经元中的钠漏通道（NALCN）对挥发性麻醉剂镇痛效果的贡献。结果光遗传或化学遗传沉默 CeA 神经元降低了异氟醚或七氟烷在体内的镇痛效果。在接触镇痛浓度的异氟烷或七氟烷时，CeAGABA神经元的钙信号增加。敲除 CeAGABA 神经元中的 NALCN 可减弱异氟醚、七氟烷或两者的镇痛作用。例如，异氟醚、七氟醚或二者的平均浓度均显著增加，从而诱发对尾搔刺激的不动（异氟醚：1.17 [0.05] vol% vs 1.24 [0.04] vol%，P=0.01；七氟醚：2.65 [0.07] vol% vs 2.81 [0.07] vol%；P<0.001）。在脑片中，异氟醚、七氟醚或两者的临床浓度都会增加 CeAGABA 神经元中 NALCN 介导的保持电流和电导，从而以 NALCN 依赖性方式增加 CeAGABA 神经元的兴奋性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of anaesthesia 医学-麻醉学

CiteScore

13.50

自引率

7.10%

发文量

488

审稿时长

27 days

期刊介绍： The British Journal of Anaesthesia (BJA) is a prestigious publication that covers a wide range of topics in anaesthesia, critical care medicine, pain medicine, and perioperative medicine. It aims to disseminate high-impact original research, spanning fundamental, translational, and clinical sciences, as well as clinical practice, technology, education, and training. Additionally, the journal features review articles, notable case reports, correspondence, and special articles that appeal to a broader audience. The BJA is proudly associated with The Royal College of Anaesthetists, The College of Anaesthesiologists of Ireland, and The Hong Kong College of Anaesthesiologists. This partnership provides members of these esteemed institutions with access to not only the BJA but also its sister publication, BJA Education. It is essential to note that both journals maintain their editorial independence. Overall, the BJA offers a diverse and comprehensive platform for anaesthetists, critical care physicians, pain specialists, and perioperative medicine practitioners to contribute and stay updated with the latest advancements in their respective fields.