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We investigated whether EA alleviates neuropathic pain by suppressing metabotropic glutamate receptor 5 (mGluR5) signaling in the anterior cingulate cortex (ACC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In na\u00efve mice, we manipulated ACC pyramidal neurons using adeno\u2010associated viral (AAV) vectors encoding calcium\/calmodulin\u2010dependent protein kinase II (CaMKII)\u2010driven opsins\u2014channelrhodopsin\u20102 (ChR2) or halorhodopsin (NpHR3.0)\u2014followed by blue\u2010 or yellow\u2010light stimulation to assess behavioral responses. In a chronic constriction injury (CCI) model, mice received EA and were evaluated for mechanical and thermal withdrawal thresholds. Western blotting (WB) and immunofluorescence (IF) quantified ACC mGluR5 expression. Then CaMKII\u2010targeted adeno\u2010associated viruses expressing chemogenetic receptors, such as hM3Dq or hM4Di, were injected into the ACC. Two weeks later, CCI was induced, and mice received either EA or intraperitoneal clozapine\u2010N\u2010oxide (CNO) while pain behaviors were monitored. Finally, proteomic profiling of ACC tissue compared CCI and EA groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Optogenetic activation of ACC pyramidal neurons in na\u00efve mice reduced both mechanical and thermal withdrawal thresholds, indicating a pronociceptive effect, whereas optogenetic inhibition increased thresholds. In CCI mice, EA significantly attenuated hypersensitivity and downregulated ACC mGluR5 protein levels by WB and IF. Chemogenetic inhibition of ACC pyramidal neurons similarly elevated thresholds in CCI mice, imitating EA. Notably, combining chemogenetic inhibition with EA produced no additional improvement, suggesting convergence on a common ACC mGluR5\u2010dependent pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EA relieves neuropathic pain in mice, at least in part, by suppressing ACC pyramidal neuron activity via inhibition of mGluR5 signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/np\/9427819","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:17:36Z","timestamp":1778678256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroacupuncture Relieves Neuropathic Pain by Suppressing ACC Pyramidal Activity via mGluR5 Inhibition in CCI 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