Mi Zhang,1 Ningbo Li,2 Shuai Zhao,1 Xiaobo Feng1,3 

1Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, People’s Republic of China; 2Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Pain Medicine, Zhongnan Hospital, Wuhan University, Wuhan, 430071, People’s Republic of China

Correspondence: Xiaobo Feng, Email fengxb@whu.edu.cn Shuai Zhao, Email shuaizhao@whu.edu.cn

Abstract: Poorly treated acute pain can develop into chronic pain, resulting in significant impairment of patients’ quality of life. The hyperalgesic priming model is commonly used to study how acute pain transforms into chronic pain. Inflammatory factors, small molecules, opioid receptor agonists, chemotherapy drugs, and stress serve as initiating factors in the hyperalgesic priming model. Various signaling pathways such as PKCϵ, MOR and ephrin-B2 pathways, and sexual differences also contribute to the transformation process of chronic pain. In this review, we examine various hyperalgesic priming models and their underlying molecular mechanisms. By thoroughly investigating these molecular mechanisms, researchers can more precisely identify the critical nodes involved in pain transformation, thereby developing more targeted treatment strategies.

Keywords: transition from acute to chronic pain, hyperalgesic priming, experimental models, molecular pathways, sex differences