Producing micturition by combined afferent and effernet electrical stimulation

描述(由申请人提供)：脊髓损伤(SCI)等神经疾病引起的发病率的主要原因之一是对下尿路失去控制。脊髓损伤导致失去对膀胱排空的自主控制，储存过程中膀胱过度活动(膀胱反射亢进)，膀胱和尿路括约肌同时收缩(膀胱-括约肌协同失调)，而不是以协调的方式。膀胱-括约肌协同失调妨碍尿液完全排出，产生高膀胱压力，需要每日导尿。这些事件可能导致尿路感染、大小便失禁和膀胱输尿管返流，继而造成肾脏损害。这些问题导致生活质量下降，医疗费用高昂，并对患者及其家人造成严重的社会和心理负面影响。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，只有当结合不可逆地切断感觉神经根(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，才能恢复膀胱排尿。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。拟议项目的目标是开发一种神经假体，以恢复膀胱功能，而不需要背根切断术。我们提出了一种创新的方法，使用传入(感觉)刺激，利用现有的脊髓回路来产生排尿。我们之前已经证明，电刺激感觉神经可以引起膀胱收缩并产生排尿。本项目将演示使用感觉刺激和运动刺激相结合来产生排尿的可行性。这种方法将消除背根切断术的需要，如果成功，可以迅速进入临床部署。将在患有脊髓损伤的动物和人身上进行补充实验，以量化这种方法的有效性，并将动物模型结果转化为人类可行性研究。这种恢复膀胱排尿的方法有望增加我们对传入介导的下尿路神经生理学的了解，更重要的是，增加受益于神经假体膀胱控制的人数，以改善他们的健康和生活质量，同时降低医疗系统的成本。

DESCRIPTION (provided by applicant): One of the leading causes of morbidity resulting from neurological disorders such as spinal cord injury (SCI) is the loss of control over the lower urinary tract. SCI results in loss of voluntary control of bladder evacuation, bladder overactivity during storage (bladder hyper-reflexia) and the bladder and urethral sphincter contract simultaneously (bladder-sphincter dysynergia) instead of in a coordinated manner. Bladder-sphincter dysynergia prevents complete elimination of urine, generates high bladder pressure and requires daily urethral catheterization. These events can lead to urinary tract infections, incontinence and vesico-ureteral reflux with ensuing kidney damage. These problems result in a decreased quality of life, large medical costs and a substantial negative social and psychological impact on patients and their families. 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 the proposed project is to develop a neural prosthesis to restore bladder function that does not require a dorsal rhizotomy. We propose an innovative approach using afferent (sensory) stimulation that exploits the existing spinal circuitry to produce voiding. We have previously shown that electrical stimulation of sensory nerves can evoke bladder contractions and produce voiding. This project will demonstrate the feasibility of using sensory stimulation combined with motor stimulation to produce voiding. This approach would eliminate the need for a dorsal rhizotomy and, if successful, can be rapidly moved into clinical deployment. Complementary experiments will be conducted in animals and people with SCI to quantify the effectiveness of this approach and to translate animal model results to human feasibility studies. This approach to restoration of bladder voiding is expected to increase our understanding of afferent-mediated neurophysiology of the lower urinary tract and, more importantly, to increase the number of people who benefit from neuroprosthetic bladder control to improve their health and quality of life while reducing costs to the healthcare system.