An ACC-VTA-ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences

被引：54

作者：

Song, Qian ^{[1
,2
,3
]}

Wei, Anqi ^{[1
,2
]}

Xu, Huadong ^{[1
,2
,4
,5
]}

Gu, Yuhao ^{[1
,2
]}

Jiang, Yong ^{[6
]}

Dong, Nan ^{[1
,2
]}

Zheng, Chaowen ^{[1
,2
]}

Wang, Qinglong ^{[7
,8
,9
,10
]}

Gao, Min ^{[7
,8
,9
,10
]}

Sun, Suhua ^{[7
,8
,9
,10
]}

Duan, Xueting ^{[1
,2
]}

Chen, Yang ^{[1
,2
]}

Wang, Bianbian ^{[1
,2
]}

Huo, Jingxiao ^{[1
,2
]}

Yao, Jingyu ^{[1
,2
]}

Wu, Hao ^{[1
,2
]}

Li, Hua ^{[1
,2
]}

Wu, Xuanang ^{[1
,2
]}

Jing, Zexin ^{[1
,2
]}

Liu, Xiaoying ^{[1
,2
]}

Yang, Yuxin ^{[1
,2
]}

Hu, Shaoqin ^{[1
,2
]}

Zhao, Anran ^{[1
,2
]}

Wang, Hongyan ^{[4
,5
,11
]}

Cheng, Xu ^{[4
,5
]}

Qin, Yuhao ^{[4
,5
]}

Qu, Qiumin ^{[3
]}

Chen, Tao ^{[12
,13
]}

Zhou, Zhuan ^{[7
,8
,9
,10
]}

Chai, Zuying ^{[14
]}

Kang, Xinjiang ^{[4
,5
,6
,11
]}

Wei, Feng ^{[15
,16
]}

Wang, Changhe ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Xi An Jiao Tong Univ, Inst Mitochondrial Biol & Med, Key Lab Biomed Informat Engn, Neurosci Res Ctr,Sch Life Sci & Technol,Minist Ed, Xian, Peoples R China

[2] Xi An Jiao Tong Univ, Core Facil Sharing Platform, Xian, Peoples R China

[3] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurol, Xian, Peoples R China

[4] Southwest Med Univ, Key Lab Med Electrophysiol, Minist Educ China, Collaborat Innovat Ctr Prevent & Treatment Cardio, Luzhou, Peoples R China

[5] Southwest Med Univ, Inst Cardiovasc Res, Luzhou, Peoples R China

[6] Southwest Med Univ, Affiliated Hosp, Dept Neurosurg, Luzhou, Peoples R China

[7] Peking Univ, Coll Future Technol, Inst Mol Med, State Key Lab Membrane Biol, Beijing, Peoples R China

[8] Peking Univ, Coll Future Technol, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing, Peoples R China

[9] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China

[10] Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing, Peoples R China

[11] Liaocheng Univ, Coll Life Sci, Liaocheng, Shandong, Peoples R China

[12] Fourth Mil Med Univ, Dept Human Anat Histol & Embryol, Xian, Peoples R China

[13] Fourth Mil Med Univ, KK Leung Brain Res Ctr, Xian, Peoples R China

[14] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA

[15] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA

[16] Univ Maryland, Program Neurosci, Ctr Adv Chron Pain Res, Baltimore, MD 21201 USA

来源：

NATURE NEUROSCIENCE | 2024年 / 27卷 / 02期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

ANTERIOR CINGULATE CORTEX; DOPAMINE NEURONS; ANXIETY; NUCLEUS; MECHANISMS; DEPRESSION; PLASTICITY; BEHAVIOR; HYPERSENSITIVITY; NOCICEPTION;

D O I：

10.1038/s41593-023-01519-w

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACC(Glu)) projecting to the VTA indirectly inhibit dopaminergic neurons (VTA(DA)) by activating local GABAergic interneurons (VTA(GABA)), and this effect is reinforced after nerve injury. VTA(DA) neurons in turn project to the ACC and synapse to the initial ACC(Glu) neurons to convey feedback information from emotional changes. Thus, an ACC(Glu)-VTA(GABA)-VTA(DA)-ACC(Glu) positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive- like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.

引用

页码：272 / +

页数：33

共 85 条

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