首页|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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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 excit-ability 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.
Yi Yan、Mengye Zhu、Xuezhong Cao、Gang Xu、Wei Shen、Fan Li、Jinjin Zhang、Lingyun Luo、Xuexue Zhang、Daying Zhang、Tao Liu
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Department of Pain Medicine,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China
Institute of Pain Medicine,Jiangxi Academy of Clinical and Medical Sciences,Nanchang 330006,China
Key Laboratory of Neuropathic Pain,Healthcare Commission of Jiangxi Province,Nanchang 330006,China
Center for Experimental Medicine,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China
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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Jiangxi ProvinceNatural Science Foundation of Jiangxi Province
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