{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:08:02Z","timestamp":1767204482181,"version":"build-2238731810"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Central neuroinflammation is pivotal in neuropathic pain pathogenesis, with blood-spinal cord barrier (BSCB) dysfunction recognized as a trigger for neuroinflammation and pain, though molecular mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Through comparative clinical studies measuring serum endoglin in postherpetic neuralgia (PHN) patients versus healthy controls, and animal investigations using spared nerve injury (SNI) rat models with recombinant endoglin intervention, we assessed mechanical\/thermal hyperalgesia, microglial activation, inflammatory cytokines, BSCB permeability, and TGF-\u03b2RI\/Smad2\/NR2B phosphorylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PHN patients exhibited lower serum endoglin versus controls; SNI rats showed reduced spinal endoglin compared to sham controls. Recombinant endoglin alleviated hyperalgesia while reversing microglial activation, inflammation, BSCB impairment, and NR2B phosphorylation. SNI decreased spinal TGF-\u03b2RI expression and Smad2 phosphorylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that endoglin reduction disrupts BSCB integrity via TGF-\u03b2\/Smad2 pathway inhibition in endothelial cells, driving microglial activation, neuroinflammation, and NR2B phosphorylation, thereby elucidating a key pain mechanism and identifying endoglin as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2025.1603619","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T05:28:33Z","timestamp":1757914113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endoglin alleviates neuropathic pain by protecting the blood\u2013spinal cord barrier through the TGF-\u03b2\/Smad2 signaling pathway"],"prefix":"10.3389","volume":"18","author":[{"given":"SiJing","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei-Ran","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gui-Fang","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hq","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The blood-brain barrier: an overview: structure, regulation, and clinical implications","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. 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