The projections from the anterior cingulate cortex to the nucleus accumbens and ventral tegmental area contribute to neuropathic pain-evoked aversion in rats

NEUROBIOLOGY OF DISEASE

卷:140

Article

Gao, Shi-Hao^1,2  Shen, Lin-Lin²  Wen, Hui-Zhong¹  Zhao, Yan-Dong¹  Chen, Peng-Hui¹  Ruan, Huai-Zhen¹ 

[1] Army Med Univ, Coll Basic Med Sci, Dept Neurobiol, Chongqing Key Lab Neurobiol, 30 Gaotanyan St, Chongqing 400038, Peoples R China

[2] Army Med Univ, Xinqiao Hosp, Army Hosp 953, Shigatse Branch, Shigatse 857000, Peoples R China

关键词: Anterior cingulate cortex;    Aversive therapy;    Neuropathic pain;    Nucleus accumbens;    Ventral tegmental area;   

DOI  :  10.1016/j.nbd.2020.104862

来源: Elsevier

【 摘 要 】

Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10-14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.