Jing Zhang, Yang Zhang, Jingxue Zhao, Jifei Sun, Xiaoxu Zhang
Chronic pain is a prevalent health issue with high disability rates, and traditional pharmacological treatments often come with limitations such as dependency and side effects. Transcutaneous auricular vagus nerve stimulation (taVNS), as an emerging non-invasive neuromodulation technique, has demonstrated broad application prospects in chronic pain management in recent years. This systematic review examines the clinical efficacy of taVNS across multiple chronic pain conditions, including neuropathic pain, autoimmune disease-related pain, gastrointestinal pain, and musculoskeletal pain. It also delves into its neurobiological mechanisms, primarily involving activation of central descending pain control pathways, modulation of cholinergic anti-inflammatory pathways, balancing autonomic nervous system function, reshaping functional connectivity in brain networks, regulating neurotransmitter and neuropeptide balance, and inhibiting peripheral and central sensitization processes. Despite ongoing challenges in parameter standardization, in-depth mechanism elucidation, and personalized treatment strategies, taVNS offers an innovative therapeutic approach for chronic pain patients due to its favorable safety profile, tolerability, and multi-target regulatory advantages. Future large-scale clinical studies and multidisciplinary collaboration are needed to further advance the precision application of taVNS within comprehensive pain management systems.