Langdale Christopher L, Hokanson James A, Sridhar Arun, Grill Warren M
Department of Biomedical Engineering, Duke University, Durham, North Carolina.
Bioelectronics Research and Development, GlaxoSmithKline, Stevenage, United Kingdom.
Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F657-F665. doi: 10.1152/ajprenal.00116.2017. Epub 2017 Jun 14.
Overactive bladder (OAB) syndrome is a highly prevalent condition that may lead to medical complications and decreased quality of life. Emerging therapies focusing on selective electrical stimulation of peripheral nerves associated with lower urinary tract function may provide improved efficacy and reduced side effects compared with sacral neuromodulation for the treatment of OAB symptoms. Prior studies investigating the effects of pelvic nerve (PelN) stimulation on lower urinary tract function were focused on promoting bladder contractions, and it is unclear whether selective stimulation of the PelN would be beneficial for the treatment of OAB. Therefore our motivation was to test the hypothesis that PelN stimulation would increase bladder capacity in the prostaglandin E (PGE) rat model of OAB. Cystometry experiments were conducted in 17 urethane-anesthetized female Sprague-Dawley rats. The effects of intravesical PGE vs. vehicle and PelN stimulation after intravesical PGE on cystometric parameters were quantified. Intravesical infusion of PGE resulted in decreased bladder capacity and increased voiding efficiency without a change in bladder contraction area under the curve, maximum contraction pressure, or contraction duration. Bladder capacity was also significantly decreased compared with vehicle (1% ethanol in saline) confirming that the change in bladder capacity was mediated by PGE PelN stimulation reversed the PGE-induced change in bladder capacity and increased the external urethral sphincter electromyogram activity at a specific stimulation condition (amplitude of 1.0 times threshold at 10 Hz). These results confirm that the urodynamic changes reported in conscious rats are also observed under urethane anesthesia and that PelN stimulation is a novel and promising approach for the treatment of the symptoms of OAB.
膀胱过度活动症(OAB)综合征是一种高度普遍的病症,可能导致医学并发症并降低生活质量。与骶神经调节相比,专注于选择性电刺激与下尿路功能相关的外周神经的新兴疗法可能会提供更高的疗效并减少副作用,用于治疗OAB症状。先前研究盆腔神经(PelN)刺激对下尿路功能的影响主要集中在促进膀胱收缩,而选择性刺激PelN对治疗OAB是否有益尚不清楚。因此,我们的动机是检验在OAB的前列腺素E(PGE)大鼠模型中,PelN刺激会增加膀胱容量这一假设。在17只经乌拉坦麻醉的雌性Sprague-Dawley大鼠中进行了膀胱测压实验。定量膀胱内注入PGE与赋形剂后以及膀胱内注入PGE后PelN刺激对膀胱测压参数的影响。膀胱内注入PGE导致膀胱容量减小和排尿效率增加,而曲线下膀胱收缩面积、最大收缩压力或收缩持续时间无变化。与赋形剂(盐水中1%乙醇)相比,膀胱容量也显著减小,证实膀胱容量的变化是由PGE介导的。PelN刺激逆转了PGE诱导的膀胱容量变化,并在特定刺激条件下(10Hz时幅度为阈值的1.0倍)增加了尿道外括约肌肌电图活动。这些结果证实,在乌拉坦麻醉下也观察到了清醒大鼠中报告的尿动力学变化,并且PelN刺激是一种治疗OAB症状的新颖且有前景的方法。