title: Combination histamine and serotonin treatment after simulated childbirth injury improves stress urinary incontinence.
abstract: Histamine and serotonin-related 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.
  
  
  
  Twenty-six age-matched female rats underwent pudendal nerve crush and vaginal distension (PNC + VD), to produce SUI. One week after injury, rats were treated subcutaneously with saline, histamine (1.1 μg), serotonin (2μg), or the combination of both twice daily for another week. A sham injured group received sham PNC + VD and were treated with saline (n = 7). 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-way ANOVA and Student-Newman-Keuls posthoc test with P < 0.05 indicating statistically significant differences between groups.
  
  
  
  Combination treatment significantly increased LPP after PNC + VD 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.
  
  
  
  Combination treatment was the most effective and may provide an effective therapy for SUI. Neurourol. Urodynam. 35:703-710, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.|Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.|Advanced Platform Technology Rehabilitation R&D Center of Excellence, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.
authors.forename: Qi-Xiang
authors.initials: QX
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.|Advanced Platform Technology Rehabilitation R&D Center of Excellence, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.|Biology Department, University of Akron, Akron, Ohio.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Balog
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.|Advanced Platform Technology Rehabilitation R&D Center of Excellence, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.
authors.forename: Dan Li
authors.initials: DL
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.|Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Jiang
authors.affiliation: Beech Tree Labs, Inc.,, Providence, Rhode Island.
authors.forename: Volkan
authors.initials: V
authors.lastname: Gurel
authors.affiliation: Biological Support Services, Louisiana Tech University, Ruston, Louisiana.
authors.forename: James
authors.initials: J
authors.lastname: Spaulding
authors.affiliation: Biological Support Services, Louisiana Tech University, Ruston, Louisiana.
authors.forename: Julia
authors.initials: J
authors.lastname: Tobacyk
authors.affiliation: Beech Tree Labs, Inc.,, Providence, Rhode Island.
authors.forename: John
authors.initials: J
authors.lastname: McMichael
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic, Cleveland, Ohio.|Advanced Platform Technology Rehabilitation R&D Center of Excellence, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.|Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Margot S
authors.initials: MS
authors.lastname: Damaser
mesh_terms: D000818:Animals; D001720:Birth Injuries / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000627:therapeutic use*; D009409:Nerve Crush / Q000009:adverse effects*; D060525:Pudendal Nerve / Q000293:injuries*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014521:Urethra / Q000187:drug effects; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000209:etiology
chemical_list: D012701:Serotonin; D006632:Histamine
keywords: electromyography; external urethral sphincter; female; histology; leak point pressure; rat