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Bladder pain accompanying cyclophosphamide (<jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>)\u2010induced cystitis in mice has been shown to involve the functional upregulation of the <jats:styled-content style=\"fixed-case\">CSE<\/jats:styled-content>\/H<jats:sub>2<\/jats:sub>S\/Ca<jats:sub>v<\/jats:sub>3.2 pathway. Therefore, we investigated whether <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB, as an upstream signal of the <jats:styled-content style=\"fixed-case\">CSE<\/jats:styled-content>\/H<jats:sub>2<\/jats:sub>S system, contributes to bladder pain in mice with <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>\u2010induced cystitis. Bladder pain\u2010like nociceptive behaviour was observed in <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>\u2010treated mice, and referred hyperalgesia was evaluated by the von Frey test. Isolated bladder weights were assessed to estimate bladder swelling, and protein levels were measured by Western blotting. <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>, administered intraperitoneally, induced nociceptive behaviour, referred hyperalgesia and increased bladder weights in mice. \u03b2\u2010Cyano\u2010<jats:sc>l<\/jats:sc>\u2010alanine, a reversible selective <jats:styled-content style=\"fixed-case\">CSE<\/jats:styled-content> inhibitor, prevented <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>\u2010induced nociceptive behaviour, referred hyperalgesia, and, in part, increases in bladder weight. <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content> markedly increased phosphorylated <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65 levels in the bladder, an effect that was prevented by pyrrolidine dithiocarbamate (<jats:styled-content style=\"fixed-case\">PDTC<\/jats:styled-content>), an <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB inhibitor. <jats:styled-content style=\"fixed-case\">PDTC<\/jats:styled-content> and curcumin, which inhibits <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB signals, abolished <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>\u2010induced nociceptive behaviour, referred hyperalgesia and, in part, increases in bladder weight. <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content> caused the overexpression of <jats:styled-content style=\"fixed-case\">CSE<\/jats:styled-content> in the bladder, and this was prevented by <jats:styled-content style=\"fixed-case\">PDTC<\/jats:styled-content> or curcumin. The <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>\u2010induced activation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB signals appeared to cause <jats:styled-content style=\"fixed-case\">CSE<\/jats:styled-content> overexpression in the bladder, contributing to bladder pain and in part swelling, possibly through H<jats:sub>2<\/jats:sub>S\/Ca<jats:sub>v<\/jats:sub>3.2 signaling. Therefore, <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB\u2010inhibiting compounds including curcumin may be useful for the treatment of cystitis\u2010related bladder pain.<\/jats:p>","DOI":"10.1111\/1440-1681.12875","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T12:12:43Z","timestamp":1508242363000},"page":"355-361","source":"Crossref","is-referenced-by-count":12,"title":["Involvement of <scp>NF<\/scp>\u2010\u03baB in the upregulation of cystathionine\u2010\u03b3\u2010lyase, a hydrogen sulfide\u2010forming enzyme, and bladder pain accompanying cystitis in mice"],"prefix":"10.1111","volume":"45","author":[{"given":"Tomoka","family":"Ozaki","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology and Pathophysiology Faculty of Pharmacy Kindai University  Higashi\u2010Osaka 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