Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus.
10.1007/s12264-022-00989-5
- Author:
Yi YAN
1
;
Mengye ZHU
1
;
Xuezhong CAO
1
;
Gang XU
1
;
Wei SHEN
1
;
Fan LI
1
;
Jinjin ZHANG
1
;
Lingyun LUO
1
;
Xuexue ZHANG
2
;
Daying ZHANG
3
;
Tao LIU
4
Author Information
1. Department of Pain Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
2. Department of Pain Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. zxx2006666@163.com.
3. Department of Pain Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. zdysino@163.com.
4. Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. liutao1241@ncu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Electrophysiology;
HCN2 channel;
Neuropathic pain;
Optogenetics;
Thalamocortical circuit
- MeSH:
Animals;
Mice;
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics*;
Neuralgia;
RNA, Small Interfering;
Thalamus/metabolism*;
Up-Regulation
- From:
Neuroscience Bulletin
2023;39(5):774-792
- CountryChina
- Language:English
-
Abstract:
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.
