Differential modulation of pain and associated anxiety by GABAergic neuronal circuits in the lateral habenula

• 成果类型: Article
• 署名作者: Chen, Teng; Liu, Wen-Bo; Zhu, Sheng-Jie; Aji, Abudula; Zhang, Chen; Zhang, Chao-Chen; Duan, Yu-Jie; Zuo, Jia -Xin; Liu, Zhe-Chen; Li, Hao-Jun; Wang, Yu-Quan; Mi, Wen-Li; Mao-Ying, Qi -Liang; Wang, Yan-Qing; Chu, Yu-Xia
• 署名单位: Fudan University; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Fudan University; Fudan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9039
• DOI: 10.1073/pnas.24094431211
• 发表日期: 2024-11-26
• 关键词: paraventricular nucleus; estrogen-receptor; facilitation; DEPRESSION; thalamus; rat

摘要

Persistent pain frequently precipitates the development of anxiety disorders, yet the underlying mechanisms are not fully understood. In this study, we employed a mouse model that simulates trigeminal neuralgia and observed a marked reduction in the activity of GABAergic neurons in the lateral habenula (LHb), a critical region for modulating pain and anxiety. We utilized precise optogenetic and chemogenetic techniques to modulate these neurons, which significantly alleviated behaviors associated with pain and anxiety. Our investigations revealed an inhibitory pathway from the LHb GABAergic neurons to the posterior paraventricular thalamus. Activation of this pathway primarily tions between GABAergic and glutamatergic neurons within the LHb were essential in alleviating both pain and anxiety following trigeminal nerve damage. Additionally, estrogen receptor alpha, providing dual therapeutic effects for both pain and anxiety. These in the intersection of pain and anxiety, pointing to promising therapeutic possibilities.