Bladder Voiding via Pudendal Nerve Block

通过阴部神经阻滞实现膀胱排尿

• 批准号: 7750312
• 负责人: Kenneth J. Gustafson
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7750312
• 关键词: Action Potentials; Acute; Address; American; Animal Experiments; Animal Model; Animals; Ataxia; Autonomic Dysreflexia; Autopsy; Bilateral; Bladder; Bladder Control; Bladder Dysfunction; Brain Stem Infarctions; Cerebral Palsy; Chronic; Clinical; Clinical Trials; Data; Development; Devices; Disabled Persons; Disease; Dorsal; Economics; Education; Effectiveness; Electric Stimulation; Electrodes; Esthesia; Evaluation; FPS-FES Oncogene; Family; Feasibility Studies; Frequencies; Future; Goals; Grant; Health; Healthcare Systems; Hospitalization; Human; Hyperreflexia; Implant; Implanted Electrodes; Incontinence; Individual; Injury; Intestines; Kidney; Kidney Transplantation; Lead; Left; Leisure Activities; Life Style; Lower urinary tract; Measures; Medical; Medical Device; Methods; Modeling; Monitor; Morbidity - disease rate; Motor; Multiple Sclerosis; Muscle Spasticity; Nerve; Nerve Block; Nervous System Trauma; Neurogenic Bladder; Operative Surgical Procedures; Paralysed; Patients; Performance; Personal Satisfaction; Persons; Phase; Plant Roots; Population; Procedures; Production; Prosthesis; Quality of life; Recurrence; Reflex action; Renal dialysis; Research; Research Design; Research Methodology; Rhizotomy procedure; Sacral nerve; Safety; Sensory; Sex Functioning; Societies; Sphincter; Spinal Cord; Spinal cord injury; Stimulus; Stroke; System; Technology; Testing; Tissues; Translating; United States; Urethral sphincter; Urinary Calculi; Urinary tract infection; Urination; Veterans; Work; abstracting; afferent nerve; chronic pain; clinical application; clinically significant; cost; disability; experience; implantable device; improved; nervous system disorder; neural prosthesis; novel strategies; pressure; prevent; programs; public health relevance; reflex urine incontinence; relating to nervous system; response; restoration; social; transmission process; urinary; urologic

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.

描述（由申请人提供）： 通过阴部神经阻滞实现膀胱排尿 - 项目摘要/摘要 目的和研究目的：神经损伤或脊髓损伤 (SCI)、脑干中风和多发性硬化症等疾病后的膀胱功能障碍可能对患者及其家人产生毁灭性影响，导致给个人和社会带来高昂的成本。该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。这些疾病可导致尿道括约肌反射性活动，从而阻止排尿并导致肾损伤和自主神经反射障碍。尿道括约肌或支配括约肌的阴部神经的手术切除可以减少这些并发症，但可能导致尿失禁、性功能和感觉丧失。研究设计和方法：本研究提出了一种利用阴部神经高频（HF）电传导阻滞来产生膀胱排尿的新方法。电神经阻滞提供了一种立即、可逆的方法来阻断动作电位传播。在我们当前的优点审查中，我们证明了阴部神经的高频电阻滞，从而在膀胱激活过程中尿道外括约肌（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 动物中产生排尿的长期有效性和安全性，这些动物表现出与患有 SCI 的人类相似的膀胱括约肌协同失调。神经袖带电极将放置在阴部神经上，以允许高频阻滞尿道括约肌，并放置在骶根上，以允许动物的膀胱驱动。将监测有效神经阻滞和排尿功效的刺激参数 8 周。表现出稳定且有效的阴部高频阻滞和排尿的动物将被脊椎化。植入的电极随后将用于排空；因此，植入系统将成为管理这些动物膀胱功能的主要手段。将确定联合阴部高频阴部阻滞和骶根激活以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高频波形的反应。临床意义：该项目的成功完成将为将我们在动物模型中发现的最新进展转化为患有 SCI 的退伍军人迈出重要一步。这将支持未来对能够恢复膀胱功能的植入神经假体进行人体可行性测试。这种方法预计将扩大可以受益于控制膀胱的神经假体的人群，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高频阻滞的理解，并将其扩展到其他医学应用，例如慢性疼痛、中风引起的肌肉痉挛和脑瘫。 公共卫生相关性： 通过阴部神经阻滞实现膀胱排尿 - 项目叙述拟议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、福祉和功能独立性。尽管约 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。除了使人衰弱和代价高昂之外，瘫痪还会损害工作、参与社交或休闲活动、接受教育或参与与独立和富有成效的生活方式相关的其他活动的能力。 SCI 和其他导致神经源性膀胱的残疾，如多发性硬化症和中风，会导致泌尿系统并发症，如失禁、尿路感染、肾损伤，以及随后的肾透析或移植可能导致反复住院且费用昂贵。该项目通过提供一种按需膀胱排空的方法，直接解决患有 SCI 或神经系统疾病的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为将这种方法转化为临床实施提供所需的数据，并导致开发有效的神经假体来恢复膀胱功能。此外，高频神经阻滞对许多其他临床应用（例如慢性疼痛、肌肉痉挛等）未来潜在的巨大临床影响增加了这项工作的价值。