Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (10): 2838-2854.doi: 10.4103/NRR.NRR-D-24-00429

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Lu Guan1, 2, #, Mengting Qiu3, #, Na Li1, #, Zhengxiang Zhou1, #, Ru Ye1 , Liyan Zhong1 , Yashuang Xu1 , Junhui Ren1 , Yi Liang1, 2, Xiaomei Shao1, 2, Jianqiao Fang1, 2, *, Junfan Fang1, 2, *, Junying Du1, 2, *   

  1. 1 Department of Neurobiology and Acupuncture Research, Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China;  2 Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China;  3 Fuchun Community Health Service Center of Fuyang District, Hangzhou, Zhejiang Province, China
  • Online:2025-10-15 Published:2025-02-07
  • Contact: Junfan Fang, PhD, fangjunfan0223@163.com; Jianqiao Fang, PhD, fangjianqiao7532@163.com; Junying Du, PhD, dujunying0706@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82374561 (to JD), 82174490 (to JF); the Medical and Health Science and Technology Program of Zhejiang Province, No. 2021RC098 (to JD); and the Research Project of Zhejiang Chinese Medical University, Nos. 2022JKZKTS44 (to JD), 2022FSYYZZ07 (to JF).

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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 painrelated 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.

Key words: anterior cingulate cortex,  anxiety,  chronic pain,  circuit,  communication,   comorbidity,  depression,  gamma-aminobutyric acidergic neurons,  parvalbumin neurons,   synaptic transmission