{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T22:32:45Z","timestamp":1759617165118},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,15]],"date-time":"2018-08-15T00:00:00Z","timestamp":1534291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK0093496","AR049610"],"award-info":[{"award-number":["DK0093496","AR049610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To develop a rodent model of persistent non\u2010inflammatory bladder pain and to test macrophage migration inhibitory factor and high mobility box group\u00a01 as mediators of bladder pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female C57BL\/6 mice received intravesical instillations of protease activated receptor\u00a04 (100\u00a0\u03bcmol\/L, for 1\u00a0h) three times every other day and abdominal mechanical hypersensitivity (50% mechanical threshold) was tested on day\u00a00 (baseline), and at days\u00a01, 2, 3, 4, 7 and 9 after the first protease\u2010activated receptor\u00a04 injection. At the end of the experiment, micturition changes were measured and bladders were examined for histological changes. Macrophage migration inhibitory factor antagonist (MIF098; 40\u00a0mg\/kg i.p. b.i.d.) or high mobility group box\u00a01 inhibitor (glycyrrhizin; 50\u00a0mg\/kg i.p. daily) was administered from day\u00a02 until day\u00a08.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a significant and persistent decrease in abdominal mechanical threshold starting from day\u00a03 in the protease\u2010activated receptor\u00a04\u2010treated group that persisted until day\u00a09 (5\u00a0days post\u2010last instillation), but not in the control group. Glycyrrhizin fully reversed while MIF098 partially reversed abdominal mechanical hypersensitivity in protease\u2010activated receptor\u00a04\u2010treated mice. The changes started on day\u00a03 after the first protease\u2010activated receptor\u00a04 instillation, and analgesic effects lasted throughout the rest of the testing period. None of the groups had significant micturition changes or overt bladder histological changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Repeated intravesical protease activated receptor\u00a04 instillations produce persistent bladder pain without inflammation. Macrophage migration inhibitory factor and high mobility group box\u00a01 are possible effective target molecules for bladder pain alleviation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.13778","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T05:10:21Z","timestamp":1534396221000},"page":"887-893","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Protease activated\u2010receptor\u00a04 activation as a model of persistent bladder pain: Essential role of macrophage migration inhibitory factor and high mobility group box\u00a01"],"prefix":"10.1111","volume":"25","author":[{"given":"Fei","family":"Ma","sequence":"first","affiliation":[{"name":"Research and Development Lexington Veterans Affairs Medical Center Lexington Kentucky USA"},{"name":"Department of Physiology University of Kentucky Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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