Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain

Molecular Brain

Xiao-ming Jin¹  Fang-bing Shao²  Si-si Wang²  Meng-ting Qiu²  Jun-fan Fang²  Dan-ning Xi²  Xiao-mei Shao²  Jian-qiao Fang²  Yi Liang²  Zui Shen²  Jun-ying Du²  Jing-gen Liu³ 

[1] Department of Anatomy and Cell Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, NB Building, 320w 15th Street #141, 46202, Indianapolis, IN, USA;Department of Neurobiology and Acupuncture Research, the Third School of Clinical Medicine, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, 310053, Hangzhou, China;Department of Neurobiology and Acupuncture Research, the Third School of Clinical Medicine, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, 310053, Hangzhou, China;Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China;

关键词: Chronic inflammatory pain;    Anxiety-like behavior;    GABAergic system;    Anterior cingulate cortex;    synaptic transmission;   

DOI  :  10.1186/s13041-021-00849-9

来源: Springer

【 摘 要 】

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

【 授权许可】

CC BY