Single-neuron projectome-guided analysis reveals the neural circuit mechanism underlying endogenous opioid antinociception

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外文摘要：Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain,but its underlying circuit mechanism remains largely unknown.Here,we showed that endogenous opioid antinociception required the activation of mu-opioid receptors(MORs)in GABAergic neurons of the central amygdala nucleus(CEA)in a persistent-hyperalgesia mouse model.Pharmacogenetic suppression of these CEAMOR neurons,which mimics the effect of MOR activation,alleviated the persistent hyperalgesia.Furthermore,single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons,each innervating distinct target brain regions.We found that the suppression of axon branches projecting to the parabrachial nucleus(PB)of one subtype of CEAMOR neurons alleviated persistent hyperalgesia,indicating a subtype-and axonal-branch-specific mechanism of action.Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception.Thus,this study identified the central neural circuit that underlies endogenous opioid antinociception,providing new insight into the endogenous pain modulatory mechanisms.

外文关键词：

endogenous opioid antinociceptionmu-opioid receptorscentral amygdala nucleusparabrachial nucleussingle-neuron projectome

作者：

Yan-Nong Dou、Yuan Liu、Wen-Qun Ding、Qing Li、Hua Zhou、Ling Li、Meng-Ting Zhao、Zheng-Yi-Qi Li、Jing Yuan、Xiao-Fei Wang、Wang-Yuan Zou、Anan Li、Yan-Gang Sun

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作者单位：

Institute of Neuroscience,Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology,CAS Center for Excellence in Brain Science &Intelligence Technology,Chinese Academy of Sciences,Shanghai 200031,China

Department of Biology,School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China

Lingang Laboratory,Shanghai 200031,China

University of Chinese Academy of Sciences,Beijing 100049,China

Britton Chance Center for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics,MoE Key Laboratory for Biomedical Photonics,Huazhong University of Science and Technology,Wuhan 430074,China

Department of Anesthesiology,Xiangya Hospital,Central South University,Changsha 410008,China

HUST-Suzhou Institute for Brainsmatics,JITRI,Suzhou 215123,China

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基金：

National Science and Technology Innovation 2030 Major ProgramNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShanghai Municipal Science and Technology Major ProjectYangFan projectYouth Innovation Promotion Association,Chinese Academy of Sciences

项目编号：

2021ZD020440482271244322210032018SHZDZX0521YF14532002022266

出版年：

2024

DOI：

10.1093/nsr/nwae195

国家科学评论(英文版)

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ISSN：

年,卷(期)：2024.11(7)