{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:18:04Z","timestamp":1791271084750,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T00:00:00Z","timestamp":1387756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Cyclophosphamide induces urotoxicity characterized by the development of cystitis, which involves bladder overactivity and inflammation. Here, we investigated the roles of chemokine receptor 2 (CXCR2) and transient receptor potential vanilloid 1 (<jats:styled-content style=\"fixed-case\">TRPV1<\/jats:styled-content>) channels in a rat model of cyclophosphamide\u2010induced cystitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Cystitis induced by cyclophosphamide in rats was assessed by gross morphology, histology and immunohistochemistry of bladder tissue. mRNA for CXCR2 and TRPV1 channels were measured by RT\u2010PCR. Nociceptive responses in paw and abdomen, along with cystometric measures were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Cyclophosphamide, i.p., induced pain behaviour, bladder inflammation and voiding dysfunction. The <jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content> antagonist, <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>225002, the <jats:styled-content style=\"fixed-case\">TRPV1<\/jats:styled-content> channel antagonist, <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>366791 or their combination reduced the mechanical hypersensitivity of paw and abdominal area and nociceptive behaviour after cyclophosphamide. Cyclophosphamide\u2010induced cystitis was characterized by haemorrhage, oedema, neutrophil infiltration and other inflammatory changes, which were markedly decreased by the antagonists. Up\u2010regulation of <jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TRPV1 mRNA<\/jats:styled-content> in the bladder after cyclophosphamide was inhibited by SB225002, <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>366791 or their combination. Expression of <jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content> and TRPV1 channels was increased in the urothelium after cyclophosphamide. Bladder dysfunction was shown by increased number of non\u2010voiding contractions (<jats:styled-content style=\"fixed-case\">NVCs<\/jats:styled-content>) and bladder pressures and a reduction in bladder capacity (<jats:styled-content style=\"fixed-case\">BC<\/jats:styled-content>), voided volume (<jats:styled-content style=\"fixed-case\">VV<\/jats:styled-content>) and voiding efficiency (<jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>225002 or its combination with <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>366791 reduced bladder pressures, whereas <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>225002, <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>366791 or their combination increased <jats:styled-content style=\"fixed-case\">BC<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">VV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>, and also reduced the number of <jats:styled-content style=\"fixed-case\">NVCs<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content> and TRPV1 channels play important roles in cyclophosphamide\u2010induced cystitis in rats and could provide potential therapeutic targets for cystitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12467","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T11:21:20Z","timestamp":1381749680000},"page":"452-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Role of <scp>CXCR2<\/scp> and <scp>TRPV1<\/scp> in functional, inflammatory and behavioural changes in the rat model of cyclophosphamide\u2010induced haemorrhagic 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