Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion
Lu Guan
Mengting Qiu
Na Li
Zhengxiang Zhou
Ru Ye
Liyan Zhong
Yashuang Xu
Junhui Ren
Yi Liang
Xiaomei Shao
Jianqiao Fang
Junfan Fang
Junying Du
Abstract：Pain is often comorbid with emotional disorders such as anxiety and depression. Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission. This review primarily aims to outline the main circuitry (including the input and output connectivity) of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons; it also describes the neurotransmitters/neuromodulators affecting these neurons, their intercommunication with other neurons, and their importance in mental comorbidities associated with chronic pain disorders. Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions. However, the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive. It is also unclear as to whether the mechanisms are presynaptic or postsynaptic. Further exploration of the complexities of this system may reveal new pathways for research and drug development.
Keywords：anterior cingulate cortexanxietychronic paincircuitcommunicationcomorbiditydepressiongamma-aminobutyric acidergic neuronsparvalbumin neuronssynaptic transmission
Publication Date：2025-10-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：17( 2838-2854 )