Bladder Voiding via Pudendal Nerve Block

通过阴部神经阻滞的膀胱排尿-项目总结/摘要 目的和研究目的：神经损伤或脊髓损伤（SCI）等疾病后的膀胱功能障碍， 脑干中风和多发性硬化症会对患者及其家人产生毁灭性的影响， 对个人和社会的代价。这项研究计划的长期目标是开发神经假体， 恢复神经系统疾病患者的完整下尿路功能;特别是SCI。这些疾病可以 导致反射性尿道括约肌活动，其可阻止排尿并导致肾损伤和自主神经反射异常。 手术切除尿道括约肌或支配括约肌的阴部神经可以减少这些 并发症，但可能导致排尿和排便功能，性功能和感觉的丧失。 研究设计和方法：本研究提出了一种新的方法，利用高频（HF）电传导 阻断阴部神经以产生膀胱排泄。电神经阻滞提供了一个即时的，可逆的 阻断动作电位传播的方法。在我们当前的Merit审查期间，我们已经证明高频电气 在膀胱激活期间，阴部神经的阻断以及由此的尿道外括约肌（EUS）的阻断可产生 膀胱排尿相当于阴部神经切断。这些结果表明，电神经阻滞可以 在急性动物实验中恢复排尿功能，并且使用阴部神经阻滞的神经假体是可行的。 该提案将进行将这些结果转化为临床实施所需的研究。具体来说，我们将 确定这种方法在慢性SCI动物中产生排尿的慢性有效性和安全性， 膀胱括约肌协同失调与SCI患者相似。将神经袖带电极放置在阴部神经上， 允许HF阻断尿道括约肌，并在骶骨根上允许膀胱驱动动物。刺激参数 有效的神经阻滞和排尿功效将被监测8周。证明稳定和有效的动物 阴部HF阻滞和排泄将被棘化。然后，植入的电极将用于排尿;因此， 植入系统将是管理这些动物膀胱功能的主要手段。的有效性 将确定联合阴部HF阴部阻滞和骶根激活以提供膀胱排空。神经 功能和组织学测量将用于确定神经组织对慢性HF波形的反应。 临床意义：本项目的成功完成将为我们最近的翻译迈出重要的一步。 在脊髓损伤退伍军人的动物模型中发现的进展。这将支持未来的人类可行性测试， 能够恢复膀胱功能的植入神经假体。预计这一做法将扩大人口， 个人谁可以受益于神经假体控制膀胱，从而提高他们的健康和质量 同时降低医疗保健系统的成本。该项目还将提高我们对HF块的理解， 扩展到其他医疗应用，如慢性疼痛，中风和脑瘫的肌肉痉挛。

Bladder Voiding via Pudendal Nerve Block - Project Summary/Abstract Objectives and Research Aims: Bladder dysfunction after neurological injury or disorders such as spinal cord injury (SCI), brainstem stroke, and multiple sclerosis can have a devastating impact on patients and their families, resulting in a high cost to the individual and to society. The long-term goal of this research program is to develop neural prostheses to restore complete lower urinary tract function in persons with neurological disorders; particularly SCI. These disorders can result in reflex urethral sphincter activity that can prevent voiding and lead to renal damage and autonomic dysreflexia. Surgical section of the urethral sphincter or the pudendal nerves that innervate the sphincter can reduce these complications but may result in loss of urinary and fecal continence, sexual function and sensation. Research Design and Methods: This study proposes a new approach utilizing high frequency (HF) electrical conduction block of the pudendal nerves to produce bladder voiding. Electrical nerve block provides an immediate, reversible approach to block action potential propagation. During our current Merit Review we have demonstrated that HF electrical block of the pudendal nerves, and thereby the external urethral sphincter (EUS) during bladder activation can produce bladder voiding equivalent to pudendal nerve transection. These results demonstrate that electrical nerve block can restore voiding function in acute animal experiments and that a neural prosthesis using pudendal nerve block is feasible. This proposal will conduct the studies needed to translate these results into clinical implementation. Specifically, we will determine the chronic efficacy and safety of this approach to produce voiding in chronic SCI animals that demonstrate bladder-sphincter dyssynergia similar to humans with SCI. Nerve cuff electrodes will be placed on the pudendal nerves to allow HF block of the urethral sphincter, and on the sacral roots to allow bladder drive in animals. Stimulus parameters for effective nerve block and voiding efficacy will be monitored for 8 weeks. Animals that demonstrate stable and effective pudendal HF block and voiding will be spinalized. The implanted electrodes will then be used for voiding; therefore the implanted system will be the primary means of managing bladder function in these animals. The effectiveness of combined pudendal HF pudendal block and sacral root activation to provide bladder emptying will be determined. Nerve function and histologic measures will be used to determine the neural tissue responses to the chronic HF waveforms. Clinical Significance: Successful completion of this project will take an important step towards translating our recent advances discovered in animal models to veterans with SCI. This will support future human feasibility testing of an implanted neural prosthesis able to restore bladder function. This approach is expected to expand the population of individuals who could benefit from neural prostheses to control the bladder, and thereby improve their health and quality of life while reducing costs to the healthcare system. This project will also improve our understanding of HF block that can be expanded to other medical applications such as chronic pain, muscle spasticity in stroke and cerebral palsy.