Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral  

作　　者：Yi Yan Mengye Zhu Xuezhong Cao Gang Xu Wei Shen Fan Li Jinjin Zhang Lingyun Luo Xuexue Zhang Daying Zhang Tao Liu 

机构地区：[1]Department of Pain Medicine,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China [2]Institute of Pain Medicine,Jiangxi Academy of Clinical and Medical Sciences,Nanchang 330006,China [3]Key Laboratory of Neuropathic Pain,Healthcare Commission of Jiangxi Province,Nanchang 330006,China [4]Center for Experimental Medicine,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China

出　　处：《Neuroscience Bulletin》2023年第5期774-792,共19页神经科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81960216,81903595,81860216,and 32060186)and the Natural Science Foundation of Jiangxi Province(20202BABL206049 and 20202BAB216043).

摘　　要：The thalamocortical(TC)circuit is closely asso-ciated 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 trac-ing,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 pharmaco-logical 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.

关 键 词：Neuropathic pain Thalamocortical circuit HCN2 channel OPTOGENETICS Electrophysiology 

分 类 号：R743.3[医药卫生—神经病学与精神病学]