{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:00Z","timestamp":1785411360296,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030680","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"crossref","award":["PL202308043V"],"award-info":[{"award-number":["PL202308043V"]}],"id":[{"id":"10.13039\/100030680","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100030680","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"crossref","award":["PL202408053V"],"award-info":[{"award-number":["PL202408053V"]}],"id":[{"id":"10.13039\/100030680","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PL202308043V"],"award-info":[{"award-number":["PL202308043V"]}],"id":[{"id":"https:\/\/ror.org\/04je98850","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PL202408053V"],"award-info":[{"award-number":["PL202408053V"]}],"id":[{"id":"https:\/\/ror.org\/04je98850","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Irene and Paul Chair Professorship, College of Medicine, Fu Jen Catholic University"},{"id":[{"id":"https:\/\/ror.org\/04je98850","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology","award":["MOST 109-2314-B-030-003-My3"],"award-info":[{"award-number":["MOST 109-2314-B-030-003-My3"]}]},{"award":["MOST 109-2314-B-030-003-My3"],"award-info":[{"award-number":["MOST 109-2314-B-030-003-My3"]}],"id":[{"id":"https:\/\/ror.org\/0031khd05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DRG adhesion is a key pathological feature of failed back surgery syndrome and a major cause of neuropathic pain. DRG, or epidural adhesion, commonly results from spinal surgery, leakage of disk material into the epidural space, or inflammation. To better mimic this clinical condition, we developed a novel and reliable animal model of DRG adhesion-induced neuropathic pain. Using this model, we investigated the therapeutic potential and underlying mechanisms of CLARIX FLO, a sterile, particulate human amniotic membrane and umbilical cord tissue product. Our results demonstrate that CLARIX FLO exerts significant analgesic and anti-inflammatory effects in the DRG adhesion model. The application of CLARIX FLO to the injured DRG markedly attenuated mechanical allodynia. CLARIX FLO treatment also reduced outer sheath thickening, suppressed the inflammatory microenvironment, and decreased hypersensitivity of isolectin B4-positive neurons. Mechanistically, CD44 was identified as a potential downstream mediator of CLARIX FLO. Furthermore, a high dose of HC-HA\/PTX3, the key bioactive component of CLARIX FLO, effectively reversed mechanical allodynia and inflammation. Notably, CLARIX FLO inhibited the overexpression of TNF-\u03b1 and TRPV1 adhering to the DRG. In this study, we demonstrated that CLARIX FLO effectively alleviates DRG adhesion-induced neuropathic pain through a CD44\u2013TRPV1-dependent mechanism.<\/jats:p>","DOI":"10.3390\/ijms27073096","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T08:22:36Z","timestamp":1774858956000},"page":"3096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CLARIX FLO Inhibits DRG Adhesion-Induced Neuropathic Pain Through the CD44\u2013TRPV1 Signaling Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Chia-Chi","family":"Kung","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"},{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ping","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-3282","authenticated-orcid":false,"given":"Chao-Chiang","family":"Tu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"},{"name":"Department of Surgery, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-An","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Heng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"},{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-2050","authenticated-orcid":false,"given":"Chao-Hsien","family":"Sung","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"},{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-8203","authenticated-orcid":false,"given":"Chun-Hsien","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-6918","authenticated-orcid":false,"given":"Chih-Li","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, No. 510 Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","article-title":"Cellular and molecular mechanisms of pain","volume":"139","author":"Basbaum","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11916-017-0629-5","article-title":"Neuropathic Pain: Central vs. Peripheral Mechanisms","volume":"21","author":"Meacham","year":"2017","journal-title":"Curr. 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