Bladder and Sphincter Control after Spinal Cord Injury

描述（由申请人提供）：下尿路的正常功能是储存和及时排尿。这些功能在脊髓损伤（SCI）后出现异常。在排尿过程中，逼尿肌和尿道括约肌同时收缩（逼尿肌括约肌协同障碍，DSD），在排尿过程中，逼尿肌也经常收缩（逼尿肌反射亢进，DH）。DSD妨碍尿液完全排出，造成膀胱高压，需要每日导尿。长期高膀胱压可引起膀胱输尿管反流和肾衰竭。残留的尿液在膀胱和尿道导尿中，引起膀胱炎和感染。此外，DH会导致膀胱储存能力低和短暂的膀胱内高压，导致尿失禁，肾脏损伤和膀胱肥大的风险。下尿路问题不仅造成了高额的医疗费用，而且给患者及其家属带来了巨大的社会和心理影响。该项目的目标是寻找治疗DSD和DH的新方法。虽然电刺激骶前根已成功地恢复脊髓损伤后的膀胱控制，但它需要骶后根横断（背根切断术）来预防DSD和DH。背根切断术具有破坏性和不可逆性，可导致反射性性功能和反射性排便功能丧失。我们的新方法将利用脊髓损伤后剩余的和新出现的脊髓反射来恢复失去的功能，而不是通过背根切断术进一步破坏神经通路。在储尿过程中，我们将电刺激阴部神经传入通路，以消除膀胱超反射性收缩，治疗DH。当尝试排尿时，我们通过轴突阻断刺激抑制阴部神经传导，放松尿道外括约肌，从而治疗DSD。采用这种方法，膀胱容量大，排尿压力低，残余尿量少。我们的方法保留了肠道和性器官的脊髓反射功能，更重要的是为脊髓损伤患者提供了从未来神经再生和修复技术的进步中获益的机会。

DESCRIPTION (provided by applicant): Normal functions of the lower urinary tract are storage and timely elimination of urine voiding. These functions are abnormal after spinal cord injury (SCI). Detrusor and urethral sphincter contract simultaneously during voiding (detrusor sphincter dyssynergia, DSD) and the detrusor also contracts frequently during storage (detrusor hyperreflexia, DH). DSD prevents complete elimination of urine, generates high bladder pressure and requires daily urethral catheterization. High bladder pressure causes vesicoureteral reflux and renal failure in the long-term. Residual urine in the bladder and urethral catheterization, cause cystitis and infection. In addition, DH causes a low bladder storage capacity and transient high intravesical pressures resulting in incontinence, risk for kidney damage and bladder hypertrophy. The problems of the lower urinary tract result in large medical cost and tremendous social and psychological impacts on the patients and their families. The goal of this project is to find new methods to treat both DSD and DH. Although electrical stimulation of sacral anterior roots has been successful to restore bladder control after SCI, it requires transection of sacral posterior roots (dorsal rhizotomy) to prevent DSD and DH. Dorsal rhizotomy is destructive and irreversible, and results in the loss of reflex sexual function and reflex defecation. Our new approach will utilize the remaining and newly emerged spinal reflexes after SCI to restore the lost functions, rather than further damaging the neural pathways by dorsal rhizotomy. During urine storage, we will electrically stimulate pudendal nerve afferent pathways to abolish the hyperreflexic bladder contractions and treat DH. When voiding is attempted, we will suppress pudendal nerve conduction with axonal blocking stimulation to relax the external urethral sphincter and thereby treat DSD. With this approach, a large bladder capacity and low pressure voiding with a minimal residual volume of urine will be expected. Our approach preserves the spinal reflex functions for bowel and sexual organ, and more importantly provides SCI patients the opportunity to benefit from advances in neural regeneration and repair techniques in the future.