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Electroacupuncture has been shown to modulate these pathways, but the underlying brain mechanisms remain unclear. This study investigated how electroacupuncture influences nociceptive-initiated and centrally maintained pain via changes in brain activation and functional connectivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In this randomized controlled trial (NCT02064296), female adults with fibromyalgia received either electroacupuncture (n\u2009=\u200919) or sham treatment with inactive laser stimulation (n\u2009=\u200925) over four weeks. Changes in brain activation and connectivity during evoked pressure-pain stimulation were assessed using functional magnetic resonance imaging before and after treatment. Here, we present\u00a0a secondary analysis of data from the trial. Clinical outcomes assessed include pressure-pain tolerance and widespread pain, and analyses tested whether brain measures mediated treatment-related effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Here we show that in the electroacupuncture group, reductions in widespread pain are associated with increases in pressure-pain tolerance. This relationship is mediated by greater activation of the primary somatosensory cortex and stronger connectivity between somatosensory and insular regions, consistent with a bottom-up mechanism linking peripheral nociceptive-initiated input to central nociplastic pain modulation. In contrast, the sham group shows reductions in widespread pain linked to decreased precuneus activity and precuneus\u2013insula connectivity, consistent with a top-down process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Electroacupuncture and sham treatments engage distinct neural pathways to influence pain perception. These findings highlight that electroacupuncture modulates nociceptive-initiated and nociplastic pain through a bottom-up sensory pathway, whereas sham treatment engages top-down control. This mechanistic dissociation may inform patient selection and optimization of acupuncture-based therapies for chronic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-025-01280-0","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T13:04:03Z","timestamp":1768050243000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Brain sensory network activity underlies reduced nociceptive initiated and nociplastic pain via acupuncture in fibromyalgia"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-6243","authenticated-orcid":false,"given":"Apeksha","family":"Sridhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishtiaq","family":"Mawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Ichesco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brock","family":"Pluimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Harte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Napadow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2067-8447","authenticated-orcid":false,"given":"Richard E.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"1280_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2165\/11630070-000000000-00000","volume":"32","author":"D Fornasari","year":"2012","unstructured":"Fornasari, D. 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