{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T09:38:13Z","timestamp":1793525893786,"version":"4.5.0"},"reference-count":70,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01RX003060"],"award-info":[{"award-number":["I01RX003060"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS105633, R01NS107262"],"award-info":[{"award-number":["R01NS105633, R01NS107262"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre\/ERT2-driven Abcc8\/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10\u2009\u00b5g IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre\/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14\u2009days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17448069211006603","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T02:23:56Z","timestamp":1617330236000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury"],"prefix":"10.1177","volume":"17","author":[{"given":"Orest","family":"Tsymbalyuk","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaida","family":"Mumtaz","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanketh","family":"Andhavarapu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas K","family":"Makar","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Maryland Health Care System, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Sansur","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Pacific Northwest Diabetes Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Bryan","sequence":"additional","affiliation":[{"name":"Pacific Northwest Diabetes Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-1988","authenticated-orcid":false,"given":"J Marc","family":"Simard","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA"},{"name":"Research Service, Veterans Affairs Maryland Health Care System, Baltimore, MD, USA"},{"name":"Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA"},{"name":"Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 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