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Chronic trigeminal neuralgia was induced by the chronic constriction of the infraorbital nerve (CION). Anxiety and depression were assessed through behavioral tests. The effects of high\u2010frequency (100\u2009Hz) and low\u2010frequency (2\u2009Hz) EA at DU20 and ST36 were compared using immunofluorescence staining to evaluate their impact on pain, anxiety, depression, and brain activity. CION induced prominent trigeminal neuralgia in mice, accompanied by anxiety\u2010 and depression\u2010like behaviors. Two weeks post\u2010CION surgery increased neural activity was observed in the Prl, Cg1, CeA, BLA, TRN, CA3, CA1, vlPAG, PC5, and LPB brain regions, while reduced activity was noted in the PVN, VTA, and LDTgv regions. EA at 100\u2009Hz applied to DU20 and ST36 rapidly alleviated pain and specifically reduced despair behavior, a depressive\u2010like phenotype. In contrast, 2\u2009Hz EA at the same acupoints addressed both anxiety\u2010 and depression\u2010like behaviors, modulating a broader range of brain regions, including the PrL, BLA, PVN, VTA, vlPAG, and LDTgv, compared to 100\u2009Hz EA. Repeated 2\u2009Hz EA exclusively at DU20 was sufficient for analgesia and improvement of anxiety and depression, demonstrating a more extensive modulation of brain activity, particularly in the VTA and LDTgv, than EA at ST36. The study reveals that CION induces significant trigeminal neuralgia, accompanied by anxiety and depression, characterized by distinct neural activity patterns. EA at 2\u2009Hz exhibits greater effectiveness in alleviating anxiety and depression, exerting broad modulation across various brain regions. Notably, EA at DU20 demonstrates superior modulation of brain activity and enhanced antidepressant and analgesic effects compared to ST36. These findings provide valuable insights into the nuanced therapeutic effects of EA on the interplay between chronic pain and affective disorders, suggesting potential clinical strategies for intervention.<\/jats:p>","DOI":"10.1096\/fj.202402461rr","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T06:26:35Z","timestamp":1737527195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Electroacupuncture effects on trigeminal neuralgia with comorbid anxiety and depression: The role of frequency and acupoint specificity"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2556-1886","authenticated-orcid":false,"given":"Zu\u2010Qi","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College Fudan University  Shanghai 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