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.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient’s rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.