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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:p>\n                    Neuropathic pain associated with central sensitization is common in diabetic patients, but the underlying mechanisms remain unclear. Here, a proteomics screen identified a previously uncharacterized protein, galectin-related protein (LGALSL), which was significantly upregulated in cerebrospinal fluid and extracellular fluid of the anterior cingulate cortex (ACC) in diabetes-related neuropathic pain (DNP) model rats. Exogenous LGALSL administration reduced mechanical nociceptive thresholds by activating glutamatergic neurons in the ACC (ACC\n                    <jats:sup>Glu<\/jats:sup>\n                    ). Chemogenetic manipulations and functional assays revealed that neuron-derived LGALSL directly binds to vimentin on ACC astrocytes, activating those astrocytes. These activated astrocytes subsequently maintain ACC\n                    <jats:sup>Glu<\/jats:sup>\n                    hypersensitivity, driving mechanical hypersensitivity in diabetic rats. Blocking LGALSL\u2013vimentin interactions with a synthetic peptide alleviated LGALSL-induced mechanical hypersensitivity. This study establishes LGALSL-dependent astrocyte-mediated hyperactivation of ACC\n                    <jats:sup>Glu<\/jats:sup>\n                    neurons as a new pathological mechanism of neuropathic pain in diabetes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2527641122","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T20:03:37Z","timestamp":1765224217000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Galectin-related protein, a key contributor, drives diabetes-associated neuropathic pain"],"prefix":"10.1073","volume":"122","author":[{"given":"Danyang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Jie","family":"Song","sequence":"additional","affiliation":[{"name":"Core Facility Centre for Life Science, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-3181","authenticated-orcid":false,"given":"Zhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]},{"name":"Department of Anatomy, Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]},{"name":"Department of Pain Medicine, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-8280","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China","place":["Hefei, 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immune mechanisms in neuropathic pain","volume":"19","author":"Fiore N. 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