Description): One of the most common symptoms of pelvic floor dysfunction is Stress Urinary Incontinence (SUL), the leakage of urine with increased stress, such as during laughing or coughing. The epidemiologic factors most strongly associated with the development of SUI are vaginal delivery and advanced age. In addition to other contributing factors, there is clinical evidence that the pudendal nerve is damaged during vaginal delivery and that women with SUI have greater nerve damage. Decrease in concentrations of circulating gonadal steroid hormones may be a precipitating factor for post-menopausal development of SUL. The long term goal of this project is to develop novel clinical methods for enhancing recovery of patients with SUL. Specifically, the neuro-anatomical and functional effects of vaginal distension will be investigated as well as the role of steroid hormones in enhancing recovery from incontinence. The hypotheses to be tested are 1. Vaginal distension causes traumatic injuries, including injury to the distal pudendal nerve, and leads to development of SUI, and 2. Treatment with gonadal steroid hormones will accelerate pudendal nerve regeneration and will lead to accelerated functional recovery of SUI after vaginal distension. These hypotheses will be tested by 4 Specific Aims: SAl. Demonstration that vaginal distension leads to incontinence symptoms followed by recovery, SA2. Demonstration that the SUI and recovery that results from vaginal distension is associated with a specific pattern of neural damage and regeneration, SA3. Determination if treatment with estrogen reduces the severity of and/or accelerates recovery from incontinence symptoms and nerve damage after vaginal distension, and SA4. Determination if treatment with dihydrotestosterone reduces the severity of and/or accelerates recovery from incontinence symptoms and nerve damage after vaginal distension.
These Specific Aims will be tested in an established animal model of vaginal distension by urodynamic testing, histological evidence, and 3u tubulin mRNA levels in pudendal motoneurons determined using in situ hybridization.
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