RT Journal Article SR Electronic T1 Modulation of Comorbid Chronic Neuropathic Pain and Anxiety-Like Behaviors by Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray and the Analgesic and Anxiolytic Effects of Electroacupuncture JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0454-23.2024 DO 10.1523/ENEURO.0454-23.2024 VO 11 IS 8 A1 Zhu, Xixiao A1 Zhang, Chi A1 Hu, Yuxin A1 Wang, Yifang A1 Xiao, Siqi A1 Zhu, Yichen A1 Sun, Haiju A1 Sun, Jing A1 Xu, Chi A1 Xu, Yunyun A1 Chen, Yuerong A1 He, Xiaofen A1 Liu, Boyu A1 Liu, Jinggen A1 Du, Junying A1 Liang, Yi A1 Liu, Boyi A1 Li, Xiaoyu A1 Jiang, Yongliang A1 Shen, Zui A1 Shao, Xiaomei A1 Fang, Jianqiao YR 2024 UL http://www.eneuro.org/content/11/8/ENEURO.0454-23.2024.abstract AB Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.