• Yaoxin Yang, Jingxuan Qiu, Jin Liu, Donghang Zhang, Mengchan Ou, Han Huang, Peng Liang, Tao Zhu, and Cheng Zhou.
• Department of Anaesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China; Research Center of Anaesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
• Br J Anaesth. 2024 Nov 1; 133 (5): 983997983-997.

BackgroundAnalgesia 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.MethodsAnalgesic 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 (CeAGABA) 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.ResultsOptogenetic or chemogenetic silencing CeA neurones reduced the analgesic effects of isoflurane or sevoflurane in vivo. The calcium signals of CeAGABA neurones increased during exposure to isoflurane or sevoflurane at analgesic concentrations. Knockdown of NALCN in CeAGABA 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 CeAGABA neurones, which increased excitability of CeAGABA neurones in an NALCN-dependent manner.ConclusionsThe analgesic potencies of volatile anaesthetics are partially mediated by modulation of NALCN in CeAGABA neurones.Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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