{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:22:00Z","timestamp":1773274920835,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,3,29]],"date-time":"2015-03-29T00:00:00Z","timestamp":1427587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Shionogi Techno Advance Research Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pain is a prominent feature of interstitial cystitis\/painful bladder syndrome (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>), but the underlying mechanisms are not fully understood. There is a lack of well\u2010characterized research tools, such as pain evaluation methods and experimental animal models, for investigating non\u2010ulcerative cystitis. We developed a novel method for evaluating bladder pain in mice with cyclophosphamide (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>)\u2010induced cystitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cystitis was produced by a single intraperitoneal injection of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> (300\u00a0mg\/kg) or repeated injections of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> (150\u00a0mg\/kg once daily for 4\u00a0days). Blunt stimulation with a cotton probe was applied to the abdominal region, and the thresholds for withdrawal responses were measured quantitatively using an anaesthesiometer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The single injection of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> provoked acute cystitis with severe bladder inflammation in mice. In these mice, we could detect an increased sensitivity to blunt stimulation, which was abolished by intravesical lidocaine. The stimulation induced phosphorylation of extracellular signal\u2010regulated kinases in bladder\u2010projecting sensory neurons. Chronic treatment with <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content> produced persistent pain responses to the blunt stimulus. Although there were few signs of bladder inflammation in these mice, the concentration of nerve growth factor (<jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>) was elevated in bladder tissue, and <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content> antiserum inhibited the hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The blunt probe method is useful for evaluating bladder pain signalling in mice, and revealed the involvement of an <jats:styled-content style=\"fixed-case\">NGF<\/jats:styled-content>\u2010sensitive pain pathway in chronic cystitis pain. This assessment method may be useful for studying the pathophysiology of bladder pain and for developing therapeutic strategies for non\u2010ulcerative <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content> in patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.693","type":"journal-article","created":{"date-parts":[[2015,3,30]],"date-time":"2015-03-30T02:59:08Z","timestamp":1427684348000},"page":"79-91","source":"Crossref","is-referenced-by-count":9,"title":["A novel method for assessing bladder\u2010related pain reveals the involvement of nerve growth factor in pain associated with cyclophosphamide\u2010induced chronic cystitis in mice"],"prefix":"10.1002","volume":"20","author":[{"given":"M.","family":"Fujita","sequence":"first","affiliation":[{"name":"Pain &amp; Neurology Discovery Research Laboratories for Core Therapeutic Areas Shionogi &amp; Co. Ltd. Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Kasai","sequence":"additional","affiliation":[{"name":"Pain &amp; Neurology Discovery Research Laboratories for Core Therapeutic Areas Shionogi &amp; Co. Ltd. Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Omachi","sequence":"additional","affiliation":[{"name":"Pain &amp; Neurology Discovery Research Laboratories for Core Therapeutic Areas Shionogi &amp; Co. Ltd. Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Pain &amp; Neurology Discovery Research Laboratories for Core Therapeutic Areas Shionogi &amp; Co. Ltd. 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