Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.
Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.
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丘脑皮质回路通过上调丘脑腹侧后外侧 HCN2 控制神经性疼痛
DOI：
10.1007/s12264-022-00989-5
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发表时间：
2023-05
影响因子：
5.6
通讯作者：
Liu, Tao
中科院分区：
文献类型：
--
作者：
Yan, Yi;Zhu, Mengye;Cao, Xuezhong;Xu, Gang;Shen, Wei;Li, Fan;Zhang, Jinjin;Luo, Lingyun;Zhang, Xuexue;Zhang, Daying;Liu, Tao
丘脑皮层（TC）回路与疼痛处理密切相关。超极化激活的环核苷酸门控（HCN）2通道主要在腹后外侧丘脑（VPL）中表达，已被证明介导神经病理性疼痛。然而，VPL HCN 2在调节TC回路活动中的作用在很大程度上是未知的。在这里，通过使用光遗传学，神经元示踪，电生理记录，和病毒敲除策略，我们表明，VPL TC神经元的激活增强了兴奋性突触传递到后肢区的初级躯体感觉皮层（S1 HL）以及机械超敏反应后，备用神经损伤（SNI）诱导的神经性疼痛小鼠。无论是药物阻断或VPL中HCN 2（shRNA-Hcn 2）的病毒敲低都足以减轻SNI诱导的痛觉过敏。此外，shRNA-Hcn 2降低TC神经元的兴奋性和VPL-S1 HL回路的突触传递。总之，我们的研究提供了一种新的机制，通过这种机制，HCN 2增强了TC回路的兴奋性，以促进神经病理性疼痛。在线版本包含补充材料，可通过10.1007/s12264-022-00989-5获得。
The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL–S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain. The online version contains supplementary material available at 10.1007/s12264-022-00989-5.
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