Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice  

作　　者：Jun-Ma Yu Rui Hu Yu Mao Yingju Tai Sen Qun Zhi Zhang Danyang Chen Yan Jin 

机构地区：[1]Department of Anesthesiology,The Third Affiliated Hospital of Anhui Medical University(The First People's Hospital of Hefei),Hefei 230061,China [2]Department of Anesthesiology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China [3]Department of Biophysics and Neurobiology,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230036,China [4]Stroke Center and Department of Neurology,TheFirst Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230036,China

出　　处：《National Science Review》2023年第2期102-117,共16页国家科学评论（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021ZD0203100);the National Natural Science Foundation of China(32025017,32121002,82171218,82101300,82101301);the CAS Project for Young Scientists in Basic Research(YSBR-013);the Youth Innovation Promotion Association CAS;the CAS Collaborative Innovation Program of Hefei Science Center(2021HSC-CIP013);the Fundamental Research Funds for the Central Universities(WK9100000030);the USTC Research Funds of the Double First-Class Initiative(YD9100002018);the Natural Science Foundation of Anhui Province(2208085J30,2008085 QC114);the Innovative Research Team of High level Local Universities in Shanghai。

摘　　要：Chronic pain is a significant problem that afflicts individuals and society,and for which the current clinical treatment is inadequate.In addition,the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized.Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus(VPL^(Glu))to the glutamatergic neurons of the hindlimb primary somatosensory cortex(S1HL^(Glu)),driving allodynia in mouse models of chronic pain.Optogenetic inhibition of this VPL^(Glu)→S1HL^(Glu)circuit reversed allodynia,whereas the enhancement of its activity provoked hyperalgesia in control mice.In addition,we found that the expression and function of the HCN2(hyperpolarization-activated cyclic nucleotide-gated channel 2)were increased in VPL^(Glu)neurons under conditions of chronic pain.Using in vivo calcium imaging,we demonstrated that downregulation of HCN2 channels in the VPL^(Glu)neurons abrogated the rise in S1HL^(Glu)neuronal activity while alleviating allodynia in mice with chronic pain.With these data,we propose that dysfunction in HCN2 channels in the VPL^(Glu)→S1HL^(Glu)thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.

关 键 词：chronic pain HCN2 channels neural circuit in vivo recordings 

分 类 号：R338.3[医药卫生—人体生理学]