Role of mast cell in hyperalgesic priming and the preventive effect of electroacupuncture on the transition from acute to chronic pain

Abstract

Objective: Injury can lead to long-term changes that increase the sensitivity of afferent nerve endings to subsequent stimulation and pain can transition from acute to chronic. This phenomenon is known as hyperalgesic priming (HP). This study aimed to understand the mechanisms underlying the effect of electroacupuncture (EA) on HP and optimize acupoint selection for EA to prevent pain transition. Methods: A rat HP model was established using sequential intraplantar injections of carrageenan (Cg) and prostaglandin E2 (PGE2). The pain thresholds were measured using von Frey filaments. EA on bilateral Zusanli (ST36) and Kunlun (BL60) was used to prevent pain transition. The number of mast cells in the ipsilateral hindpaw skin was determined using toluidine blue or fluorescence-labeled avidin staining. The protein expression levels of protein kinase C epsilon (PKCε) in the lumbar dorsal root ganglions (DRGs) were detected by western blotting 24 h after PGE2 injection. Serial pharmacological experiments were conducted to evaluate the relationship between mast cells and pain transition. Finally, EA on the bilateral ST36 and Chongyang (ST42) or a novel combination (ST36 and ST42 on the ipsilateral side, and ST36 and BL60 on the contralateral side) was used to prevent pain transition. Results: Although EA applied to ST36 and BL60 alleviated acute pain induced by Cg injection, it failed to prevent the pain transition caused by PGE2 injection. Mast cell accumulation in the ipsilateral hind paw was observed 7 days after Cg injection. Furthermore, mast cell degranulation may be responsible for PKCε activation in the DRG, a marker of pain transition. EA significantly decreased the number of mast cells in the skin of the ipsilateral hind paw when applied at ST36 and ST42, but not when applied at ST36 and BL60. Furthermore, EA employed to ST36 and ST42 significantly reversed long-term hyperalgesia induced by PGE2 injection, even when administered before injection. However, EA did not alleviate acute pain caused by Cg injection. By using a novel acupoint combination, EA simultaneously alleviated acute pain and prevented pain transition. Conclusions: Our study suggests that mast cells play a critical role in both HP and the transition from acute to chronic pain, whereas EA can prevent pain transition by decreasing the number of mast cells in the local tissue.