Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

Sisi Wang; Junying Du; Danning Xi; Fangbing Shao; Mengting Qiu; Xiaomei Shao; Yi Liang; Boyi Liu; Xiaomin Jin; Jianqiao Fang; Junfan Fang

doi:10.3389/fnins.2021.691455

Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

Front Neurosci. 2021 Jun 17:15:691455. doi: 10.3389/fnins.2021.691455. eCollection 2021.

Authors

Affiliations

¹ Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
² Department of Anatomy, Cell Biology and Physiology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.

Abstract

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA's regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E₂ (PGE₂). The decrease in mechanical withdrawal threshold (MWT) induced by PGE₂ returned to baseline 4 h after injection in NS + PGE₂ group, and still persisted 24 h after injection in Car + PGE₂ group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE₂ injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming.

Keywords: dorsal root ganglions; electroacupuncture; hyperalgesic priming; protein kinase C epsilon; γ-aminobutyric acid receptor type A.