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Managing its acute and chronic pain remains challenging. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in neuropathic and inflammatory pain, making it a potential target for CRPS\u2010I treatment. Thus, we evaluate the participation of the TRPV4 channel in nociception and spinal neuroinflammation induced by a preclinical model of CRPS\u2010I. Male mice (C57BL\/6) were used for chronic post\u2010ischemia pain (CPIP) induction. Mechanical allodynia, thermal hypersensitivity, and rotarod test were performed before (baseline) and post\u2010induction of CPIP (Days 1, 5, 10, and 15). Open field test was performed on Days 1 and 15, and nest\u2010building behavior was observed on the 15th\u201316th day after CPIP induction. The antinociceptive effect of the TRPV4 antagonist HC\u2010067047 (1\u2009mg\/kg, intraperitoneal) was evaluated over 15\u2009days. CPIP\u2010Veh (vehicle) mice exhibited mechanical allodynia and thermal hypersensitivity. HC\u2010067047 repeated treatment reduced nociception from day 5 to 15 post\u2010CPIP induction. In the open field test, CPIP\u2010Veh mice spent less time in the central zone, a parameter reversed by HC\u2010067047 treatment. Additionally, nest\u2010building scores improved with repeated treatment of HC\u2010067047. Elevated levels of putative endogenous TRPV4 ligands, hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) and nitric oxide (NO), were reduced after HC\u2010067047 repeated treatment. CPIP\u2010induced increased gene expression of spinal protease\u2010activated receptor 2 (\n                    <jats:italic>Par2<\/jats:italic>\n                    , a sensitizer of TRPV4),\n                    <jats:italic>Trpv4<\/jats:italic>\n                    , glial fibrillary acidic protein (\n                    <jats:italic>Gfap<\/jats:italic>\n                    , to evaluate astrocyte activation), and nuclear factor erythroid 2\u2013related factor 2 (\n                    <jats:italic>Nrf2<\/jats:italic>\n                    , a biomarker of antioxidant defense). HC\u2010067047 repeated treatment attenuated it, except for Trpv4 levels, which remained unaltered. These results suggest that the TRPV4 channel is likely involved in CRPS\u2010I nociceptive mechanisms in mice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70279-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70279","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:56:57Z","timestamp":1762163817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>TRPV4<\/scp>\n                    Channel Participates in the Nociception and Spinal Neuroinflammation Involved in a Model of Complex Regional Pain Syndrome Type I (\n                    <scp>CPIP<\/scp>\n                    ) in Mice"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-5479","authenticated-orcid":false,"given":"N\u00e1thaly Andrighetto","family":"Ruviaro","sequence":"first","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry Federal University of Santa Maria (UFSM)  Santa Maria Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmacology Federal University of Santa Maria (UFSM)  Santa Maria Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caren","family":"Antoniazzi","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmacology Federal University of Santa Maria 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