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.
Department of Anaesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Br J Anaesth. 2024 Nov;133(5):983-997. doi: 10.1016/j.bja.2024.06.049. Epub 2024 Sep 24.
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.
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) 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.
Optogenetic or chemogenetic silencing CeA neurones reduced the analgesic effects of isoflurane or sevoflurane in vivo. The calcium signals of CeA neurones increased during exposure to isoflurane or sevoflurane at analgesic concentrations. Knockdown of NALCN in CeA 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 neurones, which increased excitability of CeA neurones in an NALCN-dependent manner.
The analgesic potencies of volatile anaesthetics are partially mediated by modulation of NALCN in CeA neurones.
镇痛是挥发性麻醉剂的重要作用，脊髓是其关键的神经靶点。然而，中枢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）对异氟醚和七氟醚镇痛作用的贡献。
在 CeA 神经元光遗传学和化学遗传学抑制期间测试挥发性麻醉剂的镇痛效力。在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 敲低探索 GABAergic CeA（CeA）神经元中的钠泄漏通道（NALCN）对挥发性麻醉剂镇痛作用的贡献。在急性脑片上进行电生理记录，以测量 NALCN 对 CeA 神经元活性的挥发性麻醉剂调制。
CeA 神经元的光遗传学或化学遗传学沉默减少了异氟醚或七氟醚在体内的镇痛作用。在镇痛浓度下暴露于异氟醚或七氟醚时，CeA 神经元的钙信号增加。CeA 神经元中 NALCN 的敲低减弱了异氟醚、七氟醚或两者的抗伤害作用。例如，诱导尾部闪烁刺激不动的异氟醚、七氟醚或两者的平均浓度显着增加（异氟醚：1.17 [0.05] vol%比 1.24 [0.04] vol%，P=0.01；七氟醚：2.65 [0.07] vol%比 2.81 [0.07] vol%，P<0.001）。在脑片中，临床浓度的异氟醚、七氟醚或两者增加了 CeA 神经元中 NALCN 介导的保持电流和电导率，这以 NALCN 依赖的方式增加了 CeA 神经元的兴奋性。
挥发性麻醉剂的镇痛效力部分通过 CeA 神经元中 NALCN 的调制来介导。
