Pudendal Nerve Block Neural Prosthesis

描述(由申请人提供)：异常的尿路括约肌收缩可阻止膀胱排空，并在神经系统疾病或损伤后导致显著的发病率和生活质量下降。现有的治疗方法效果有限，具有破坏性或具有全身性副作用，降低了患者对这些治疗方法的接受度。电刺激骶运动神经根可以恢复脊髓损伤后的膀胱排尿；然而，只有在结合不可逆转的手术切断感觉神经根(即背根切断术)以消除否则会阻止排尿的尿道括约肌反射收缩时，才能恢复排尿。神经根切断术的其他影响(残留感觉丧失、反射性功能和反射性排便)限制了临床对该手术的接受度。该项目的目标是开发一种神经假体，它使用电阴部神经阻滞来消除尿路括约肌的激活，并允许膀胱排尿。高频神经阻滞提供快速、完全、可逆的局部神经传导阻滞。我们在动物实验中证明双侧阴部神经阻滞可以阻止尿道括约肌的激活，并产生相当于神经切断的膀胱排尿。我们还证明，阴部神经阻滞可以通过可用于人体研究的可用神经袖带电极来实现。在人类身上展示电阴部阻滞和改善排尿是将这一方法转化到人类的下一个重要里程碑。用于可行性研究的阴部神经袖套电极的植入需要FDA批准研究设备豁免(IDE)。这个第一阶段的项目将为FDA的研究设备豁免(IDE)申请确定和准备必要的组件，并与FDA举行IDE前会议。这一过程和IDE前FDA会议将确定在下一阶段(下一次应用)获得FDA批准以进行人体可行性试验所需的努力和资源。这个第一阶段的项目还将建立一个使用临时麻醉剂阴部神经阻滞的筛查程序，并确定植入装置的初始候选者。在这个第一阶段项目结束时，我们将准备好组装并提交一个集成开发环境，以便在下一阶段进行人类可行性研究。这种方法预计将扩大可以从神经假体中受益以控制膀胱的个人人口，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。 公共卫生意义：异常的尿道括约肌收缩会阻止膀胱排空。该项目开始了一种神经假体的平移，以使用尿道括约肌的阴部神经电阻滞来恢复膀胱排尿。

DESCRIPTION (provided by applicant): Abnormal urethral sphincter contractions can prevent bladder emptying and cause significant morbidity and reduction in quality of life after neurological disease or injury. Existing treatment options are of limited effectiveness, destructive, or possess systemic side effects, reducing patient acceptance of these therapies. Electrical stimulation of sacral motor nerve roots can restore bladder voiding after SCI; however only when combined with the irreversible surgical transection of the sensory spinal nerve roots (i.e., a dorsal rhizotomy) to eliminate reflex contractions of the urethral sphincter that otherwise prevent voiding. Other effects of the rhizotomy (loss of remaining sensation, reflex sexual function and reflex defecation) limit the clinical acceptance of this procedure. The goal of this project is to develop a neural prosthesis that uses electrical pudendal nerve block to eliminate urethral sphincter activation and allow bladder voiding. High frequency nerve block provides, rapid, complete and reversible local nerve conduction block. We have demonstrated that bilateral pudendal nerve block can prevent urethral sphincter activation and produce bladder voiding equivalent to nerve transection in animals. We have also demonstrated that pudendal nerve block can be achieved with available nerve cuff electrodes approvable for human studies. Demonstration of electrical pudendal block and improved voiding in humans is the next major milestone to translate this approach to humans. Implantation of a pudendal nerve cuff electrode for the feasibility study requires FDA approval of an investigational device exemption (IDE). This Phase I project will identify and prepare the necessary components for an FDA investigational device exemption (IDE) application and conduct a pre-IDE meeting with the FDA. This process and the pre-IDE FDA meeting will define the effort and resources required to obtain FDA approval to conduct the human feasibility trial in the next phase (next application). This Phase I project will also establish a screening procedure using temporary anesthetic pudendal nerve block and identify initial candidates for the implanted device. At the end of this Phase I project, we will be ready to assemble and submit an IDE to conduct the human feasibility study in the next phase. 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. PUBLIC HEALTH RELEVANCE: Abnormal urethral sphincter contractions can prevent bladder emptying. This project begins the translation of a neural prosthesis to restore bladder voiding using electrical pudendal nerve block of the urethral sphincter.