{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:09:44Z","timestamp":1790035784025,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T00:00:00Z","timestamp":1348531200000},"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":[[2012,10]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), generated by enzymes such as cystathionine\u2010\u03b3\u2010lyase (CSE) from L\u2010cysteine, facilitates pain signals by activating the Ca<jats:sub>v<\/jats:sub>3.2 T\u2010type Ca<jats:sup>2+<\/jats:sup> channels. Here, we assessed the involvement of the CSE\/H<jats:sub>2<\/jats:sub>S\/Ca<jats:sub>v<\/jats:sub>3.2 pathway in cystitis\u2010related bladder pain.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Cystitis was induced by i.p. administration of cyclophosphamide in mice. Bladder pain\u2010like nociceptive behaviour was observed and referred hyperalgesia was evaluated using von Frey filaments. Phosphorylation of ERK in the spinal dorsal horn was determined immunohistochemically following intravesical administration of NaHS, an H<jats:sub>2<\/jats:sub>S donor.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Cyclophosphamide caused cystitis\u2010related symptoms including increased bladder weight, accompanied by nociceptive changes (bladder pain\u2010like nociceptive behaviour and referred hyperalgesia). Pretreatment with DL\u2010propargylglycine, an inhibitor of CSE, abolished the nociceptive changes and partly prevented the increased bladder weight. CSE protein in the bladder was markedly up\u2010regulated during development of cystitis. Mibefradil or NNC 55\u20130396, blockers of T\u2010type Ca<jats:sup>2+<\/jats:sup> channels, administered after the symptoms of cystitis appeared, reversed the nociceptive changes. Further, silencing of Ca<jats:sub>v<\/jats:sub>3.2 protein by repeated intrathecal administration of mouse Ca<jats:sub>v<\/jats:sub>3.2\u2010targeting antisense oligodeoxynucleotides also significantly attenuated the nociceptive changes, but not the increased bladder weight. Finally, the number of cells staining positive for phospho\u2010ERK was increased in the superficial layer of the L6 spinal cord after intravesical administration of NaHS, an effect inhibited by NNC 55\u20130396.<\/jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold> Endogenous H<jats:sub>2<\/jats:sub>S, generated by up\u2010regulated CSE, caused bladder pain and referred hyperalgesia through the activation of Ca<jats:sub>v<\/jats:sub>3.2 channels, one of the T\u2010type Ca<jats:sup>2+<\/jats:sup> channels, in mice with cyclophosphamide\u2010induced cystitis.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.02060.x","type":"journal-article","created":{"date-parts":[[2012,5,31]],"date-time":"2012-05-31T03:05:10Z","timestamp":1338433510000},"page":"917-928","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Involvement of the endogenous hydrogen sulfide\/Ca<sub>v<\/sub>3.2 T\u2010type Ca<sup>2+<\/sup> channel pathway in cystitis\u2010related bladder pain in 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