Animal Model Of Stress Urinary Incontinence Research Articles

(101) SHOCKWAVE THERAPY FOR THE TREATMENT OF POSTPARTUM STRESS URINARY INCONTINENCE: A PILOT STUDY

Abstract Introduction Stress urinary incontinence (SUI) is estimated to affect approximately 15% of adult women. Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a form of electrohydraulic acoustic shockwave that has been shown to be effective in animal models of SUI. The Urogold100® is a Li-ESWT device that is FDA-cleared for improving blood flow, connective tissue activation, and pain relief, and it has been shown in multiple studies to be effective for mild to moderate erectile dysfunction and chronic pelvic pain in both men and women. While Li-ESWT has been investigated for related urologic conditions, minimal research exists as to its potential effectiveness for SUI in women. Objective Our aim was to evaluate the effectiveness of Li-ESWT for women with postpartum stress urinary incontinence in a pilot study. Methods Email recruitment was carried out in a single sexual medicine practice. Four women underwent weekly treatments with Li-ESWT for 4-6 weeks. All patients were postpartum women between ages 43-55. Treatment specifics included 1000 shocks at 2.5 Hz (initial visit) and 3.0 Hz (subsequent visits) distributed over the perineum and urethral opening. Energy level was based on patient tolerance, beginning with 0.06 Mj/mm2 and increased up to 0.08 Mj/mm2 for subsequent visits. Evaluation measures included the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bladder Diary, both administered prior to treatment initiation and after treatment completion. The ICIQ-SF allowed patients to self-assess their urine leakage over the past several weeks (amount and frequency) while the Bladder Diary required patients to record specific leakage incidences throughout a single day. Results Prior to treatment initiation, patients reported 1-3 small daily urine leaks via the NIDDK Bladder Diary. All patients either improved or remained the same in this assessment post-treatment; all patients reported 1 small daily leak after treatment completion. Results from the subjective ICIQ-SF varied: 1 patient reported worsening from 1 daily leak to 2-3 daily leaks, which she attributed to increased water intake. Two patients reported improvements (several daily leaks to 1 weekly leak; several daily leaks to 2-3 weekly leaks). One patient reported no change. Subjective reporting from patients indicated 3 of the 4 felt the treatment was improving their symptoms, and the fourth patient reported no changes. Conclusions Our pilot study indicates that 3 of 4 patients showed improvements in their objective Bladder Diary recordings with reduced frequency of urine leakage, and 2 of 4 patients noted improvements in their subjective ICIQ-SF reporting. 3 of 4 provided positive verbal feedback as well. Despite the limited sample size, the improvements seen in the objective leakage frequency recordings are encouraging findings that warrant future investigation in a larger cohort. Given the noninvasive nature, ease of use, and high patient tolerability of Li-ESWT, this treatment modality should be considered for investigation in a larger cohort with the goal of relieving symptoms of SUI. Disclosure No.

Therapeutic new targets for stress urinary incontinence in the central nervous system

Stress urinary incontinence (SUI) is a common and bothersome problem among middle-aged women. However, there are few useful drugs for SUI. Urethral hypermobility and intrinsic sphincter deficiency are two main causes of SUI. Various animal models of SUI, such as vaginal distention, pudendal nerve injury, or ovariectomy, have been developed to study the pathophysiology of SUI. In addition, we have previously reported that cerebral infarction rats also induce SUI. Leak point pressure measurements are the most commonly used methods to evaluate the urethral dysfunction in SUI animal models. Originally, we have developed microtransducer-tipped catheter measurements of urethral activity during sneezing. Previous or our basic research has clarified potential strategies for pharmacotherapy of SUI in the central nervous system. Therapeutic targets include adrenergic and serotonergic (5-HT) receptors in the spinal cord, which stimulate pudendal nerve innervating the external urethral sphincter and/or sympathetic nerve innervating urethral smooth muscle. Activation of α1-adrenoceptors, 5-HT2C, or 5-HT7 receptors enhances the reflex at the spinal cord level whereas pre- or postsynaptic α2-adrenoceptors and/or 5-HT1A receptors inhibit the reflex. We have recently reported that stimulation of the spinal μ-opioid receptors by tramadol also enhances the reflex. Thus, we review the recent advances in basic SUI research and potential targets for pharmacotherapy of SUI in the central nervous system.

The effect of a bioactive tissue‐engineered sling in a rat of stress incontinence model

In this study, we attempt to examine the feasibility of the bioactive tissue-engineered sling by using muscle precursor cells (MPCs)-seeded Poly(ε-caprolactone) (PCL) nanofiber sheet in a rat model of stress urinary incontinence (SUI). In vitro, MPCs were cultured on a PCL nanofiber sheet for one week, where the MPCs-seeded PCL nanofiber sheet showed constant twitching contraction by electrical field stimulation in an organ bath. In vivo, MPCs-seeded PCL nanofiber sheet was placed under the female rat's urethra after pudendal nerve denervation (animal model of SUI). The leak point pressure (LPP) was evaluated with the vertical tilt table after the operation for four weeks. The resulting LPP of MPCs-seeded PCL nanofiber sheet group was observed to be significantly higher than the denervation-only group's. Furthermore, PKH-26-labeled MPCs were observed under the urethral sphincter by immunohistochemistry. These results indicated that, the MPCs-seeded PCL nanofiber sheet have not only provided support for the deficient sphincter, but also actively improved the sphincter's function overall. In conclusion, this bioactive tissue-engineered sling could be used as an ideal material for the treatment of SUI.

Stem cell therapy for incontinence: where are we now? What is the realistic potential?

A significant number of women experience stress urinary incontinence (SUI), which greatly affects their quality of life. Recent research investigating utilization of stem cells and their derivatives for the prevention and treatment of SUI has been performed to test the effect of cell source and method of administration in several animal models of SUI. The type of stem cell, timing of optimal dose or doses after injury, mechanism of action of stem cells, and route of administration must be investigated both preclinically and clinically before stem cell therapy becomes a possible treatment for SUI, although the future of this therapy looks promising. This article reviews the progress in stem cell research for incontinence and describes areas of future work as suggested by research in other fields.

Models for sensory neurons of dorsal root ganglia and stress urinary incontinence

To discuss (1) animal models for investigating bladder afferent pathways from the spinal cord to the brain and (2) animal models of stress urinary incontinence (SUI) with a special emphasis on functional and histopathological characteristics of each model. Literature review of spinal mechanisms of bladder afferent pathways and animal models of SUI. Electrophysiological studies in the rat using pelvic nerve stimulation and recording of evoked potentials in the periaqueductal gray (PAG) prove to be a valuable tool to examine spinal mechanisms of bladder afferent pathways. Animal models of SUI in the rat include vaginal distention as simulated birth trauma, pudendal nerve crush or transection, urethral sphincter injury by electrocauterization, transabdominal urethrolysis, periurethral botulinum-A toxin injection, and pubo-urethral ligament transection. Functional and histopathological changes in the continence mechanism after injury are different between models. Using animal models for sensory neurons, intrathecal and intravenous administration of certain drugs can be tested whether they affect the bladder afferent pathways from the spinal cord to the PAG. Animal models of SUI can serve as a tool to develop new pharmacologic therapies or periurethral injection therapies using stem cell implants.

Animal models of stress urinary incontinence.

Stress urinary incontinence (SUI) is a common health problem significantly affecting the quality of life of women worldwide. Animal models that simulate SUI enable the assessment of the mechanism of risk factors for SUI in a controlled fashion, including childbirth injuries, and enable preclinical testing of new treatments and therapies for SUI. Animal models that simulate childbirth are presently being utilized to determine the mechanisms of the maternal injuries of childbirth that lead to SUI with the goal of developing prophylactic treatments. Methods of assessing SUI in animals that mimic diagnostic methods used clinically have been developed to evaluate the animal models. Use of these animal models to test innovative treatment strategies has the potential to improve clinical management of SUI. This chapter provides a review of the available animal models of SUI, as well as a review of the methods of assessing SUI in animal models, and potential treatments that have been tested on these models.

Neurogenic aspects of stress urinary incontinence

Vaginal childbirth is a significant risk factor for stress urinary incontinence (SUI). Women with SUI demonstrate dysfunction of the pelvic floor and pudendal nerve. Animal models of SUI have been developed to investigate its pathophysiology and for preclinical testing of potential treatments. Vaginal distension, a method of simulating childbirth injury in animals, produces a reliable decrease in leak point pressure (LPP), a measure of urethral resistance to leakage and quantification of SUI severity in animals. In addition to ischemia and direct tissue damage, vaginal distension causes denervation of the external urethral sphincter (EUS). Pudendal nerve crush produces a similar decrease in LPP, whereas combined PNC and vaginal distension injury delays recovery of LPP compared with either single injury alone. Neurophysiologic studies have elucidated the results of each injury and their combination on pudendal nerve and EUS function. Urethrolysis, electrocautery, and pudendal nerve transection produce more durable functional impairment via both structural damage and denervation. Pubourethral ligament injury eliminates the structural support of the urethra, but its neurologic effects are unknown. Animal models demonstrate a complex interplay between tissue damage and pudendal nerve dysfunction, and provide insight into the importance of neuroregeneration in the recovery of continence.

Human muscle‐derived cell injection in a rat model of stress urinary incontinence

We investigated the use of human muscle-derived cells (hMDCs) for the treatment of stress urinary incontinence (SUI) in a nude rat model. hMDCs were isolated from adult skeletal muscle. Three groups of six animals consisting of controls, animals undergoing sciatic nerve transection (SNT) with periurethral sham-injection, and SNT with hMDCs (1 x 10(6) cells/20 microl saline) were utilized. Leak point pressure (LPP) was measured 4 weeks following injection. Bilateral SNT resulted in a significantly lower LPP that was significantly higher following hMDCs than sham injection. The results demonstrate the efficacy of human muscle cell therapy alone in improving physiologic outcomes in an animal model of SUI.