Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice
作者机构：Department of Anesthesiology The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei) Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University Department of Biophysics and Neurobiology Division of Life Sciences and Medicine University of Science and Technology of China Stroke Center and Department of Neurology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China
出 版 物：《National Science Review》 (国家科学评论(英文版))
年 卷 期：2023年第10卷第2期
页 面：107-122页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
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
主 题：chronic pain HCN2 channels neural circuit in vivo recordings
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(VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex(S1HLGlu),driving allodynia in mouse models of chronic pain.Optogenetic inhibition of this VPLGlu→S1HLGlucircuit 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 VPLGluneurons under conditions of chronic pain.Using in vivo calcium imaging,we demonstrated that downregulation of HCN2 channels in the VPLGluneurons abrogated the rise in S1HLGluneuronal activity while alleviating allodynia in mice with chronic pain.With these data,we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGluthalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.
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