{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T20:12:17Z","timestamp":1772914337887,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Gout is a common cause of inflammatory arthritis and is provoked by the accumulation of monosodium urate (MSU) crystals. However, the underlying mechanisms of the pain associated with acute attacks of gout are poorly understood. The aim of this study was to evaluate the role of transient receptor potential ankyrin 1 (TRPA\u20101) and TRPA\u20101 stimulants, such as H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, in a rodent model of MSU\u2010induced inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MSU or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> was injected into the hind paws of rodents or applied in cultured sensory neurons, and the intracellular calcium response was measured in vitro. Inflammatory or nociceptive responses in vivo were evaluated using pharmacologic, genetic, or biochemical tools and methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TRPA\u20101 antagonism, TRPA\u20101 gene deletion, or pretreatment of peptidergic TRP\u2010expressing primary sensory neurons with capsaicin markedly decreased MSU\u2010induced nociception and edema. In addition to these neurogenic effects, MSU increased H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> levels in the injected tissue, an effect that was abolished by the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010detoxifying enzyme catalase. H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, but not MSU, directly stimulated sensory neurons through the activation of TRPA\u20101. The nociceptive responses evoked by MSU or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> injection were attenuated by the reducing agent dithiothreitol. In addition, MSU injection increased the expression of TRPA\u20101 and TRP vanilloid channel 1 (TRPV\u20101) and also enhanced cellular infiltration and interleukin\u20101\u03b2 levels, and these effects were blocked by TRPA\u20101 antagonism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that MSU injection increases tissue H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, thereby stimulating TRPA\u20101 on sensory nerve endings to produce inflammation and nociception. TRPV\u20101, by a previously unknown mechanism, also contributes to these responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38112","type":"journal-article","created":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T20:32:52Z","timestamp":1375734772000},"page":"2984-2995","source":"Crossref","is-referenced-by-count":78,"title":["Transient Receptor Potential Ankyrin 1 Receptor Stimulation by Hydrogen Peroxide Is Critical to Trigger Pain During Monosodium Urate\u2013Induced Inflammation in Rodents"],"prefix":"10.1002","volume":"65","author":[{"given":"Gabriela","family":"Trevisan","sequence":"first","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carin","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateus F.","family":"Rossato","sequence":"additional","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariane A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael P.","family":"Ineu","sequence":"additional","affiliation":[{"name":"Federal University of Santa Maria Santa Maria, RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo P.","family":"Guerra","sequence":"additional","affiliation":[{"name":"Federal University of Technology of Paran\u00e1, Medianeira Campus Medianeira, PR 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