Neuromodulation of Individual Pelvic Floor Muscle Activity in Urinary Incontinence

罗梅罗-奥尔特加+ ! 总结 骨盆底肌肉（PFM）形成一个圆顶形的肌肉复合体，在泌尿系统中至关重要， 排便和性功能，并削弱骨盆底肌肉可导致不受控制的逼尿肌 活动、尿急和尿失禁（UI），这是一种影响美国30-60%女性的疾病。 最近，人们日益认识到， 骨盆底的拮抗肌，并认识到功能失调的时间，减少幅度或 个别肌肉的活动模式紊乱，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，选择性和协调性刺激， 个别PFM神经将重新建立其正常的强度和活动模式，有效地扭转了 UI的症状为此，我们已经建立了一个UI的兔子模型，它复制了 人体状况，包括个别肛提肌和会阴肌激活的特定模式 在储存和排泄阶段。这项建议是创新的，因为它使用了最先进的 微型化的无线电极，使小PFM传出神经的接口，并直接 调节它们的个体活动。我们的初步研究表明， 多胎或老化引起的兔PFM活性改变，可使用选择性PFM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 力和有限的疲劳，2）评估模式的PFM活动的有效性，通过SPNM在 年轻的经产动物和年老的经产动物，以及3）证明慢性电刺激 PFM神经可以长期改善UI症状，并测试停止后SPNM益处是否持续 神经调节治疗这一建议将提供新的信息的生理作用， PFM的泌尿功能，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UI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.