Activation of parabrachial nucleus- ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice

被引：42

作者：

Zhang, Ludi ^{[1
]}

Wang, Jing ^{[1
,2
]}

Niu, Chenxu ^{[1
]}

Zhang, Yu ^{[1
]}

Zhu, Tiantian ^{[1
]}

Huang, Dongyang ^{[1
]}

Ma, Jing ^{[1
]}

Sun, Hui ^{[1
,3
]}

Gamper, Nikita ^{[1
,4
]}

Du, Xiaona ^{[1
]}

Zhang, Hailin ^{[1
]}

机构：

[1] Hebei Med Univ, Dept Pharmacol, Key Lab Neural & Vasc Biol, Key Lab New Drug Pharmacol & Toxicol,Minist Educ, Shijiazhuang 050017, Hebei, Peoples R China

[2] Hebei Univ Chinese Med, Dept Pharmacochem, Shijiazhuang 050091, Hebei, Peoples R China

[3] Binzhou Med Univ, Dept Physiol, Yantai 264003, Shandong, Peoples R China

[4] Univ Leeds, Fac Biol Sci, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England

来源：

CELL REPORTS | 2021年 / 37卷 / 05期

基金：

中国国家自然科学基金; 英国惠康基金;

关键词：

MIDBRAIN DOPAMINERGIC-NEURONS; FOS-LIKE IMMUNOREACTIVITY; LATERAL HABENULA; SOCIAL DEFEAT; SUBNUCLEAR LOCALIZATION; REWARD; SYSTEM; INPUTS; SUSCEPTIBILITY; ORGANIZATION;

D O I：

10.1016/j.celrep.2021.109936

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Depression symptoms are often found in patients suffering from chronic pain, a phenomenon that is yet to be understood mechanistically. Here, we systematically investigate the cellular mechanisms and circuits underlying the chronic-pain-induced depression behavior. We show that the development of chronic pain is accompanied by depressive-like behaviors in a mouse model of trigeminal neuralgia. In parallel, we observe increased activity of the dopaminergic (DA) neuron in the midbrain ventral tegmental area (VTA), and inhibition of this elevated VTA DA neuron activity reverses the behavioral manifestations of depression. Further studies establish a pathway of glutamatergic projections from the spinal trigeminal subnucleus caudalis (Sp5C) to the lateral parabrachial nucleus (LPBN) and then to the VTA. These glutamatergic projections form a direct circuit that controls the development of the depression-like behavior under the state of the chronic neuropathic pain.

引用

页数：21

共 67 条

[1] Comorbid depression, chronic pain, and disability in primary care [J].