Bladder, Urethra and Anal Sphincter Reinnervation

描述（由申请人提供）：在脊髓损伤患者中，恢复膀胱和肠功能非常重要，在截瘫患者中，这被认为比恢复行走功能更重要。下运动神经元损伤导致弛缓性膀胱麻痹的患者不能使用功能性电刺激（FES）诱导膀胱排空，因为脊髓和膀胱之间的神经连接已被破坏。这些患者需要新的神经通路来重新控制膀胱功能。这些研究的目的是为人体试验提供最终的证据负担的体神经转移，以神经支配膀胱。本建议旨在实现以下具体目标：具体目标1：确定生殖股（GF）神经转移到骨盆神经的前囊分支是否重新支配内括约肌平滑肌以及逼尿肌。确定自主神经壁内神经节和平滑肌细胞是否在功能上重新受到神经支配。这些研究将检验这样的假设：从转移的GF神经通过骨盆神经的膀胱分支生长到膀胱中的新神经可能一直到达尿道，以重新神经支配内平滑肌括约肌和外骨骼肌括约肌。 具体目标2：确定单侧GF至囊泡神经转移是否为膀胱排空提供与双侧神经转移一样多的功能性神经再支配。这种神经转移的临床应用将是单侧进行的，这一目的将检验单侧神经转移为膀胱排空功能提供足够的神经再支配的假设。 具体目标3：确定在骶椎去膀胱神经支配后，GF神经转移至骨盆神经膀胱分支是否会发生无FES的自发性膀胱排空。如果在神经转移后自发膀胱排空功能恢复，则不需要植入FES系统。这一目的测试的假设，GF神经再支配膀胱，中枢神经系统开发替代途径，诱导膀胱排空。 具体目标4：确定尿道和肛门括约肌是否也可以通过股前神经到阴部神经转移手术进行神经再支配。控制尿和粪便排泄可能需要新的神经通路到尿道和肛门括约肌。该目的将检验以下假设：用股前神经再支配阴部神经将允许尿道和肛门括约肌再支配，并恢复排尿和排便功能。 公共卫生相关性：本提案中所述研究的目标是开发一种手术方法，以重新神经支配下运动神经元损伤的膀胱，使患者能够重新控制膀胱排空。这些研究旨在为体神经转移以再神经支配膀胱的人体试验提供最终的证据。

DESCRIPTION (provided by applicant): In patients with spinal cord injury, regaining bladder and bowel function is of great importance, in paraplegics it is considered even more important than regaining walking function. Patents with lower motor neuron lesions resulting in flaccid bladder paralysis cannot use functional electrical stimulation (FES) to induce bladder emptying because the neural connection between the spinal cord and the bladder has been disrupted. These patients require new neural pathways to regain control of bladder function. The goal of these studies is to provide the final burden of proof for human trials of somatic nerve transfer to reinnervate the urinary bladder. This proposal is designed to achieve the following specific aims: Specific aim 1: Determine whether transfer of the genitofemoral (GF) nerve to the anterior vesicle branch of the pelvic nerve reinnervates the internal sphincter smooth muscle as well as the detrusor muscle. Determine whether both autonomic intramural ganglia and smooth muscle cells become functionally reinnervated. These investigations will test the hypothesis that the new nerves growing from the transferred GF nerve into the bladder through the vesical branch of the pelvic nerve may reach all the way down to the urethra to reinnervate the internal smooth muscle sphincter and external skeletal muscle sphincter. Specific aim 2: Determine whether unilateral GF to vesicle nerve transfer provides as much functional reinnervation for bladder emptying as the bilateral nerve transfer provides. Clinical application of this nerve transfer would be performed unilaterally and this aim will test the hypothesis that unilateral nerve transfer provides sufficient reinnervation for bladder emptying function. Specific aim 3: Determine whether spontaneous bladder emptying without FES occurs with GF nerve transfer to the vesical branch of the pelvic nerve following bladder denervation in the sacral spine. If spontaneous bladder emptying function does return after nerve transfer then implantation of the FES system would not be required. This aim tests the hypothesis that following GF nerve reinnervation of the bladder, the central nervous system develops alternate pathways that induce bladder emptying. Specific aim 4: Determine whether the urinary and anal sphincter muscles can also be reinnervated by anterior femoral to pudendal nerve transfer procedures. Control of urinary and fecal continence may require new neural pathways to the urinary and anal sphincters. This aim will test the hypothesis that reinnervation of the pudendal nerve with the anterior femoral nerve will allow both urethral and anal sphincter reinnervation and restore urinary and fecal continence. PUBLIC HEALTH RELEVANCE: The goal of the studies described in this proposal is to develop a surgical approach to reinnervate the lower motor neuron lesioned urinary bladder so the patient can regain control of bladder emptying. These studies are intended to provide the final burden of proof for human trials of somatic nerve transfer to reinnervate the urinary bladder.