Neuromodulation of Individual Pelvic Floor Muscle Activity in Urinary Incontinence

尿失禁中个体盆底肌肉活动的神经调节

基本信息

批准号：
9686834
负责人：
Mario Ignacio Romero-Ortega
金额：
$ 56.04万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9686834
关键词：
2 year old 4 year old Acute Adverse effects Affect Aging Animals Axon Birth Bladder Bladder Control Caliber Chronic Complex Defecation Devices Drug resistance Efferent Neurons Electric Stimulation Electrodes Electron Microscopy Equipment Malfunction Experimental Designs Extravasation Failure Fatigue Frequencies Functional disorder Genitourinary system Histologic Histology Human Implant Individual Intervention Measurement Measures Methods Modeling Multiparity Muscle Muscle Fibers Myelin Nerve Nerve Tissue Nulliparity Oryctolagus cuniculus Pathology Patients Pattern Pelvic Floor Muscle Pelvic floor structure Pelvis Pharmacologic Substance Phase Physiological Play Positioning Attribute Protocols documentation Rectum Recurrence Reporting Role Sacral nerve Sex Functioning Skeletal muscle structure of perineum Sphincter Symptoms Testing Thick Training Ultrasonography Urethra Urge Incontinence Urinary Incontinence Urination Urine Urodynamics Vagina Vaginal delivery procedure Wireless Technology Woman improved incontinence symptom innovation levator ani muscle miniaturize muscle aging muscle form neuroregulation neurotechnology novel pressure sensor simulation treatment effect urinary

项目摘要

Romero-Ortega+ ! Summary Pelvic floor muscles (PFM) form a dome-shaped muscle complex are critical in urinary continence, defecation and sexual functions, and weakening pelvic floor muscles can cause uncontrolled detrusor activity, urgency, and urinary incontinence (UI), a condition that affects 30-60% of women in the US. Recently, there is an increasing appreciation for the importance of the specific pattern of activity of antagonistic muscles in the pelvic floor, and a realization that dysfunctional timing, reduced amplitude or disorganized pattern of activity in individual muscles, critically impact their ability to maintain the urethra closed, resulting in urine leakage. Here, we hypothesize that selective and coordinated stimulation of individual PFM nerves will re-establish their normal strength and activity patterns, effectively reversing the symptoms of UI. To that end, we have established a rabbit model of UI that replicates several aspects of the human condition, including the specific pattern of activation of individual levator ani and perineal muscles during the storage and voiding phases. This proposal is innovative in that it uses a state-of-the-art miniaturized wireless electrodes to enable the interfacing of small PFM efferent nerves and directly modulate their individual activity. Our preliminary studies show that compromised micturition resulting from altered PFMs activity caused by multi-parity or aging in rabbits, can be reversed using selective PFM neuromodulation (SPNM). We specifically seek to: 1) define the activation parameters for maximal muscle force and limited fatigue for individual PFM, 2) evaluate the efficacy of patterned PFM activity by SPNM in young multiparous and aging multiparous animals, and 3) demonstrate that chronic electrical stimulation of PFM nerves can improved UI symptoms long-term, and test if that SPNM benefit persists after discontinuing the neuromodulation treatment. This proposal will provide new information on the physiological role of the PFM in urinary function, and will evaluate the selective neuromodulation of these muscles as a potential therapy for drug resistant UI.

罗梅罗-奥尔特加+ ！概括盆底肌肉 (PFM) 形成圆顶形肌肉复合体，对于尿失禁至关重要，排便和性功能以及盆底肌肉减弱会导致逼尿肌不受控制活动、尿急和尿失禁 (UI)，这种疾病影响着 30-60% 的美国女性。最近，人们越来越认识到特定活动模式的重要性。骨盆底的拮抗肌，并认识到时机功能失调、幅度减小或个别肌肉的活动模式混乱，严重影响其维持尿道的能力关闭，导致尿液泄漏。在这里，我们假设选择性和协调的刺激个体 PFM 神经将重新建立其正常的强度和活动模式，有效地逆转 UI 的症状。为此，我们建立了一个 UI 兔子模型，它复制了 UI 的几个方面。人类状况，包括个体提肛肌和会阴肌的特定激活模式在储存和排空阶段。该提案的创新之处在于它使用了最先进的技术小型化无线电极，可连接小型 PFM 传出神经并直接调节他们的个人活动。我们的初步研究表明，排尿困难是由于兔子的多胎或衰老引起的 PFM 活性改变可以使用选择性 PFM 来逆转神经调节（SPNM）。我们特别寻求：1）定义最大肌肉的激活参数个人 PFM 的力和有限疲劳，2) 评估 SPNM 模式化 PFM 活动的功效年轻的经产动物和老年经产动物，3）证明慢性电刺激 PFM 神经可以长期改善 UI 症状，并测试 SPNM 的益处在停止后是否持续存在神经调节治疗。该提案将提供有关生理作用的新信息 PFM 在泌尿功能中的应用，并将评估这些肌肉的选择性神经调节作为潜在的耐药 UI 的治疗。