Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury
Xixiao Zhu, Yingling Xu, Zui Shen, Haiyan Zhang, Siqi Xiao, Yichen Zhu, Mengwei Wu, Yeqing Chen, Zemin Wu, Yunyun Xu, Xiaofen He, Boyu Liu, Jinggen Liu, Junying Du, Jing Sun, Jianqiao Fang, Xiaomei Shao
Abstract
Neuropathic pain is a common cause of chronic pain and is often accompanied by negative emotions, making it complex and difficult to treat. However, the neural circuit mechanisms underlying these symptoms remain unclear. Herein, we present a novel pathway associated with comorbid chronic pain and anxiety. Using chemogenetic methods, we found that activation of glutamatergic projections from the rostral anterior cingulate cortex (rACC Glu ) to the ventrolateral periaqueductal gray (vlPAG) induced both hyperalgesia and anxiety-like behaviors in sham mice. Inhibition of the rACC Glu -vlPAG pathway reduced anxiety-like behaviors and hyperalgesia in the spared nerve injury (SNI) mice model; moreover, electroacupuncture (EA) effectively alleviated these symptoms. Investigation of the related mechanisms revealed that the chemogenetic activation of the rACC Glu -vlPAG circuit effectively blocked the analgesic effect of EA in the SNI mice model but did not affect the chronic pain-induced negative emotions. This study revealed a novel pathway, the rACC Glu -vlPAG pathway, that mediates neuropathic pain and pain-induced anxiety.