학술논문
An ACC–VTA–ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences
Document Type
Article
Author
Song, Qian; Wei, Anqi; Xu, Huadong; Gu, Yuhao; Jiang, Yong; Dong, Nan; Zheng, Chaowen; Wang, Qinglong; Gao, Min; Sun, Suhua; Duan, Xueting; Chen, Yang; Wang, Bianbian; Huo, Jingxiao; Yao, Jingyu; Wu, Hao; Li, Hua; Wu, Xuanang; Jing, Zexin; Liu, Xiaoying; Yang, Yuxin; Hu, Shaoqin; Zhao, Anran; Wang, Hongyan; Cheng, Xu; Qin, Yuhao; Qu, Qiumin; Chen, Tao; Zhou, Zhuan; Chai, Zuying; Kang, Xinjiang; Wei, Feng; Wang, Changhe
Source
Nature Neuroscience; February 2024, Vol. 27 Issue: 2 p272-285, 14p
Subject
Language
ISSN
10976256; 15461726
Abstract
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 (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADAneurons in turn project to the ACC and synapse to the initial ACCGluneurons to convey feedback information from emotional changes. Thus, an ACCGlu–VTAGABA–VTADA–ACCGlupositive-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.