ABSTRACT Pain, arising from chronic abnormal activation of nerves and tissues, contributes to dysfunction and reduced quality of life. A single mechanism and short duration of action limit the effectiveness of current local analgesics. Chinese Acupuncture (CA) influences the immune‐neural circuit by triggering mast cell (MC) degranulation at acupoints but lacks precise control. This study introduced a magnetoelectric hydrogel acupuncture system that responds to external magnetic stimulation. Using screw‐threaded needles, a hydrogel containing magnetically responsive piezoelectric nanoparticles was accurately administered to pain‐related acupoints, targeting MCs. Under magnetic fields, these nanoparticles produce coupled “mechanical force‐electrical” stimulation, promoting MC degranulation and converting physical cues into biochemical mediators acting on nerve endings to achieve analgesia. In vitro, the system enhanced Ca 2 + influx and RBL‐2H3 degranulation, leading to the secretion of mediators such as histamine, 5‐HT, and ATP. In vivo validation confirmed the system's specific activation of MCs beneath the ST‐36 acupoint, specifically triggering MC degranulation and regulating peripheral TRPV1 and dorsal root ganglia A1R expression, thus inhibiting pain transmission. Decreased proinflammatory cytokines, elevated cerebrospinal β‐endorphin, and improved pain thresholds indicated integrated immune–neuro–endocrine regulation. In conclusion, this magnetoelectric hydrogel acupuncture enables effective and sustained analgesia via controllable MC‐mediated neuroimmune modulation.
Chen et al. (Wed,) studied this question.