{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T14:51:32Z","timestamp":1774882292163,"version":"3.50.1"},"reference-count":35,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81670687"],"award-info":[{"award-number":["81670687"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:p> Bladder pain is a prominent symptom of interstitial cystitis\/painful bladder syndrome. Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) generated by cystathionine \u03b2-synthase (CBS) or cystathionine \u03b3-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H<jats:sub>2<\/jats:sub>S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H<jats:sub>2<\/jats:sub>S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H<jats:sub>2<\/jats:sub>S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H<jats:sub>2<\/jats:sub>S signaling was upregulated in PAR4-induced bladder pain models, and H<jats:sub>2<\/jats:sub>S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H<jats:sub>2<\/jats:sub>S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H<jats:sub>2<\/jats:sub>S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H<jats:sub>2<\/jats:sub>S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior. <\/jats:p>","DOI":"10.1152\/ajprenal.00526.2017","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T08:59:07Z","timestamp":1515574747000},"page":"F1077-F1086","source":"Crossref","is-referenced-by-count":13,"title":["Endogenous H<sub>2<\/sub>S sensitizes PAR4-induced bladder pain"],"prefix":"10.1152","volume":"314","author":[{"given":"Wenfu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Qilu Hospital of Shandong University, Jinan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiyu","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of First Operation Room, Qilu Hospital of Shandong University, Jinan, 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