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We propose that the efficacy of acupuncture stems from its regulatory functions that mobilize and coordinate multiple internal physiological systems at the same time. Specifically, it is mainly realized through five functional modules: (1) central network remodeling function: correcting abnormal functional connections and neural circuit activity in brain regions related to pain and emotion; (2) Neuroplasticity and repair function: activate neurotrophic pathways and synaptic regulatory mechanisms to promote neural adaptation; (3) Systematic homeostasis regulation function: balancing the interaction of neurological-endocrine-gut axes; (4) Nociceptive signal gating function: a common signaling pathway that accurately inhibits pain and negative emotions at the molecular and receptor levels; (5) Neuroimmune regulatory function : targeted inhibition of central-specific inflammatory pathways and cytokine storms. This article aims to systematically summarize the evidence from the past 5 years and clarify how these five functions constitute a synergistic treatment network, providing a new perspective for the clinical application and mechanism research of acupuncture.<\/jats:p>","DOI":"10.1177\/17448069261441012","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:19:37Z","timestamp":1776255577000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic modulation of pain-related affective disorders by acupuncture: Mechanistic review"],"prefix":"10.1177","volume":"22","author":[{"given":"Hongchun","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Acupuncture-Moxibustion, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Long","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingkun","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawen","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongxuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-0437","authenticated-orcid":false,"given":"Man","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Acupuncture-Moxibustion, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001939"},{"key":"e_1_3_2_3_2","first-page":"26","article-title":"Chronic pain and comorbid emotional disorders: neural circuitry and neuroimmunity pathways","author":"Li M","year":"2025","unstructured":"Li M, She K, Zhu P, Li Z, Liu J, Luo F, Ye Y. 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