Bladder Voiding via Pudendal Nerve Block

描述（由申请人提供）： 膀胱排尿通过阴部神经阻滞-项目摘要/摘要目标和研究目的：膀胱功能障碍后的神经损伤或疾病，如脊髓损伤（SCI），脑干中风，多发性硬化症可以有一个破坏性的影响，对患者和他们的家庭，导致在一个高成本的个人和社会。这项研究计划的长期目标是开发神经假体，以恢复神经系统疾病患者的完整下尿路功能;特别是SCI。这些疾病可导致反射性尿道括约肌活动，从而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，但可能导致大小便失禁、性功能和感觉丧失。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产生膀胱排尿。电神经阻滞提供了一种即时的、可逆的方法来阻断动作电位的传播。在我们目前的Merit审查中，我们已经证明了在膀胱激活期间，阴部神经的高频电阻滞，从而尿道外括约肌（EUS）可以产生相当于阴部神经横断的膀胱排尿。这些结果表明，电神经阻滞在急性动物实验中可以恢复排尿功能，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动物中产生排尿的长期有效性和安全性，这些动物表现出与SCI患者相似的膀胱括约肌协同失调。将神经袖带电极放置在阴部神经上以允许尿道括约肌的HF阻断，并放置在骶神经根上以允许动物的膀胱驱动。将监测有效神经阻滞和排尿疗效的刺激参数8周。表现出稳定和有效的阴部HF阻滞和排尿的动物将被脊髓化。然后将植入的电极用于排尿;因此，植入的系统将是管理这些动物膀胱功能的主要手段。将确定阴部HF阴部阻滞和骶神经根激活联合用于提供膀胱排空的有效性。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：该项目的成功完成将使我们在动物模型中发现的最新进展转化为SCI退伍军人的重要一步。这将支持未来植入的神经假体能够恢复膀胱功能的人体可行性测试。这种方法有望扩大可以从神经假体中受益的人群，从而改善他们的健康和生活质量，同时降低医疗保健系统的成本。该项目还将提高我们对HF阻滞的理解，HF阻滞可以扩展到其他医疗应用，如慢性疼痛，中风和脑瘫中的肌肉痉挛。 公共卫生相关性： 膀胱排尿通过阴部神经阻滞-项目叙述拟议的工作与退伍军人健康的相关性这项工作直接适用于残疾退伍军人的健康，福祉和功能独立。虽然大约9%的美国人是退伍军人，但他们占美国所有脊髓损伤患者的17%以上。瘫痪除了是一种使人衰弱和代价高昂的疾病外，还损害了工作、参加社交或休闲活动、接受教育或参加与独立和富有成效的生活方式有关的其他活动的能力。SCI和其他引起神经源性膀胱的残疾，如多发性硬化症和中风，导致泌尿系统并发症，如失禁、尿路感染、肾损伤，随后的肾透析或移植可能导致复发和昂贵的住院治疗。该项目通过提供一种按需膀胱排空的方法，直接解决SCI或神经系统疾病退伍军人所经历的泌尿系统并发症。这项研究的成功完成将提供将这种方法转化为临床实施所需的数据，并导致开发一种有效的神经假体来恢复膀胱功能。此外，HF神经阻滞对许多其他临床应用（如慢性疼痛、肌肉痉挛等）的潜在临床影响也增加了这项工作的价值。

DESCRIPTION (provided by applicant): 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 histological 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. PUBLIC HEALTH RELEVANCE: Bladder Voiding via Pudendal Nerve Block - Project Narrative Relevance of Proposed Work to Veterans Health This work is directly applicable to the health, well-being, and functional independence of disabled veterans. Although about 9% of Americans are veterans, they comprise over 17% of all individuals with spinal cord injuries in the United States. In addition to being a debilitating and costly condition, paralysis compromises the ability to work, engage in social or leisure activities, pursue an education, or participate in other activities associated with an independent and productive lifestyle. SCI and other disabilities causing neurogenic bladder, such as multiple sclerosis and stroke, lead to urological complications, such as incontinence, urinary tract infection, renal damage and consequent renal dialysis or transplantation can lead to recurrent and costly hospitalization. This project directly addresses the urologic complications experienced by veterans with SCI or neurological disorders by providing a means to produce on-demand bladder emptying. Successful completion of this study will provide data required to translate this approach to clinical implementation and lead to the development of an effective neural prosthesis to restore bladder function. In addition, the substantial potential future clinical impact from HF nerve block to a number of other clinical applications, such as chronic pain, muscle spasticity, etc. increases the value of this work.