Neuromodulation of Individual Pelvic Floor Muscle Activity in Urinary Incontinence

罗梅罗-奥尔特加+ 好了！ 摘要 盆底肌肉(PFM)形成的穹顶状肌肉复合体在尿失禁中起着关键作用， 排便和性功能，以及盆底肌肉的削弱会导致逼尿肌失控 活动、紧迫感和尿失禁(UI)，这是一种影响美国30%-60%女性的疾病。 最近，人们越来越多地认识到以下具体活动模式的重要性 盆底的拮抗肌肉，并意识到时机失调，幅度降低或 个体肌肉活动的无序模式，严重影响他们维持尿路的能力 封闭，导致尿液渗漏。在这里，我们假设选择性和协调的刺激 个别PFM神经将重新建立其正常的力量和活动模式，有效地逆转 尿失禁症状。为此，我们建立了一个兔子的UI模型，它复制了 人体状况，包括个别提肛肌和会阴肌肉的特定激活模式 在储存和排出阶段。这项提议是创新的，因为它使用了最先进的 微型无线电极，使小型PFM传出神经能够直接对接 调节他们的个人活动。我们的初步研究表明，由于 选择性PFM可逆转多胎或衰老引起的兔PFMS活性改变 神经调节(SPNM)。我们特别寻求：1)确定最大肌肉的激活参数 个体烤瓷修复体的作用力和极限疲劳，2)用SPNM评价模式烤瓷修复体的有效性。 年轻的经产和衰老的经产动物，以及3)证明慢性电刺激 PFM神经可以长期改善尿毒症症状，并测试停药后SPNM益处是否持续 神经调节疗法。这项提议将提供有关细胞的生理作用的新信息。 PFM对排尿功能的影响，并将评估这些肌肉的选择性神经调节作为一种潜在的 耐药尿失禁的治疗。

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.