{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:02:53Z","timestamp":1758816173144,"version":"3.41.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Beech Tree Labs, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Histamine and serotonin\u2010related pharmaceuticals have the potential to modulate micturition and continence. The aim of this study was to determine if treatment with histamine and\/or serotonin improves stress urinary incontinence (SUI) in female rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010six age\u2010matched female rats underwent pudendal nerve crush and vaginal distension (PNC\u2009+\u2009VD), to produce SUI. One week after injury, rats were treated subcutaneously with saline, histamine (1.1\u2009\u03bcg), serotonin (2\u03bcg), or the combination of both twice daily for another week. A sham injured group received sham PNC\u2009+\u2009VD and were treated with saline (n\u2009=\u20097). Leak point pressure (LPP) testing with simultaneous external urethral sphincter (EUS) electromyography (EMG) was conducted 2 weeks after injury. The urethra was harvested for qualitative and quantitative histology. Data were analyzed with a one\u2010way ANOVA and Student\u2010Newman\u2010Keuls posthoc test with<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 indicating statistically significant differences between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combination treatment significantly increased LPP after PNC\u2009+\u2009VD compared to injured sham treatment and treatment with either histamine or serotonin alone. Compared to injured sham treated rats, all three treatments significantly increased EUS EMG amplitude at both baseline and peak pressure and EUS EMG firing rate at peak pressure during LPP testing. There were more consistent urethral striated muscle fibers and thicker smooth and striated muscle with combination and histamine treatment. There was a statistically significant shift to a greater proportion of thicker collagen fibers in the urethra in serotonin and combination treated rats compared with injured sham treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combination treatment was the most effective and may provide an effective therapy for SUI.<jats:italic>Neurourol. Urodynam. 35:703\u2013710, 2016<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.22793","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T16:42:34Z","timestamp":1434559354000},"page":"703-710","source":"Crossref","is-referenced-by-count":5,"title":["Combination histamine and serotonin treatment after simulated childbirth injury improves stress urinary incontinence"],"prefix":"10.1002","volume":"35","author":[{"given":"Qi\u2010Xiang","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Cleveland Clinic Cleveland Ohio"},{"name":"Department of Urology Changhai Hospital The Second Military Medical University Shanghai People's Republic of China"},{"name":"Advanced Platform Technology Rehabilitation R&amp;D Center of Excellence Louis Stokes Cleveland Veterans Affairs Medical Center Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M.","family":"Balog","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Cleveland Clinic Cleveland Ohio"},{"name":"Advanced Platform Technology Rehabilitation R&amp;D Center of Excellence Louis Stokes Cleveland Veterans Affairs Medical Center Cleveland Ohio"},{"name":"Biology Department University of Akron Akron Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Cleveland Clinic Cleveland Ohio"},{"name":"Advanced Platform Technology Rehabilitation R&amp;D Center of Excellence Louis Stokes Cleveland Veterans Affairs Medical Center Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Cleveland Clinic Cleveland Ohio"},{"name":"Glickman Urological and Kidney Institute The Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volkan","family":"Gurel","sequence":"additional","affiliation":[{"name":"Beech Tree Labs, Inc., Providence Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Spaulding","sequence":"additional","affiliation":[{"name":"Biological Support Services Louisiana Tech University Ruston Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Tobacyk","sequence":"additional","affiliation":[{"name":"Biological Support Services Louisiana Tech University Ruston Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McMichael","sequence":"additional","affiliation":[{"name":"Beech Tree Labs, Inc., Providence Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot S.","family":"Damaser","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Cleveland Clinic Cleveland Ohio"},{"name":"Advanced Platform Technology Rehabilitation R&amp;D Center of Excellence Louis Stokes Cleveland Veterans Affairs Medical Center Cleveland Ohio"},{"name":"Glickman Urological and Kidney Institute The Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.09.081"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.13252"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8391168"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(77)90171-6"},{"key":"e_1_2_7_6_1","first-page":"5","article-title":"What do we know about duloxetine's mode of action?","volume":"113","author":"Schuessler B","year":"2006","journal-title":"Evidence from animals to humans. BJOG"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20632"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90602.2008"},{"key":"e_1_2_7_9_1","unstructured":"Safety and Efficacy Study of a New Treatment for Symptoms of Urinary Incontinence.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01340066. Last updated: March 22 2013. Last accessed: March 22 2013."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-009-0463-4"},{"key":"e_1_2_7_11_1","first-page":"97","article-title":"Collagen and Picrosirius Red Staining: A polarized light assessment of fibrillar hue and spatial distribution","volume":"22","author":"Rich L","year":"2013","journal-title":"Braz J Morphol Sci"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11934-011-0209-x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/GRF.0b013e31828563d2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11934-009-0063-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.01.094"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0031-6997(24)01328-0","article-title":"International Union of Pharmacology. XIII. Classification of histamine receptors","volume":"49","author":"Hill SJ","year":"1997","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.11.031"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705322"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-0618(96)00163-9"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656560903078410"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706504"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.691"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eursup.2004.10.004"},{"key":"e_1_2_7_24_1","article-title":"Roles of the spinal glutamatergic pathway activated through alpha\u2010amino\u20103\u2010hydroxy\u20105\u2010methylisoxazole \u20104\u2010propionic acid (AMPA) receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence mechanisms","author":"Kawamorita N","year":"2014","journal-title":"Neurourol Urodyn"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.6.F922"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/exmp.1995.1017"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.003"},{"key":"e_1_2_7_28_1","first-page":"H1007","article-title":"Contribution of collagen matrix to passive left ventricular mechanics in isolated rat hearts","volume":"266","author":"MacKenna DA","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.06.123"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041867"},{"key":"e_1_2_7_31_1","first-page":"51","article-title":"Histamine and brain","volume":"24","author":"Boissier JR","year":"1971","journal-title":"Actual Pharmacol (Paris)"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1081\/DCT-120017556"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnau.22793","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.22793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T18:10:51Z","timestamp":1748455851000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.22793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,17]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/nau.22793"],"URL":"https:\/\/doi.org\/10.1002\/nau.22793","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"type":"print","value":"0733-2467"},{"type":"electronic","value":"1520-6777"}],"subject":[],"published":{"date-parts":[[2015,6,17]]}}}