Neuromodulation for Non-Obstructive Urinary Retention (NOUR)

项目摘要 AUA最近的一份白皮书将尿潴留定义为排尿后残留量升高(PVR)300毫升 持续至少6个月，并记录在2个或更多不同的场合。虽然尿液滞留 由尿路出口梗阻引起的可以通过手术或药物治疗来解决，非 梗阻性尿潴留(NOUR)是许多临床医生面临的重大治疗挑战。目前 目前还不存在治疗努尔的有效药物。骶神经调节是FDA唯一批准的治疗方法 努尔。可改善50%(增加排尿量，降低PVR和自愈频率) 约70%的患者有长期(5-10年)的疗效。目前的机制是 目前尚不清楚是否存在骶神经调节功能。骶骨神经调节是侵入性的，需要训练有素的外科医生 植入刺激器和电极刺激S3神经根。侵袭性与外科医生 要求显著地将骶骨神经调节的影响限制在Nour的一小部分 患者，使大多数患者完全依靠每天间歇性的自我导尿排空膀胱。 间歇性自我导尿会导致频繁的下尿路感染。因此，有很大的需求。 用于基础科学研究，为努尔开发新的疗法。然而，目前很少有研究集中在 Nour，这与文献中专注于膀胱过度活动的广泛研究形成了鲜明对比 (OAB)。Nour可以是肌源性的(由逼尿肌疾病/损伤引起)、神经源性的(由神经性的) 疾病/损害)，或特发性(没有可识别的原因)。临床上，没有可识别的特发性疾病 神经/肌肉疾病/损伤包括许多中枢神经系统功能变化不明的患者。 虽然可以通过膀胱缺血或骨盆神经损伤来建立肌源性或神经源性动物模型，但它 很难建立一个没有神经/肌肉损伤的努尔动物模型，但这种动物模型是由非神经/肌肉损伤引起的。 确定中枢神经系统的功能变化(即特发性模型)。因此，在这项拨款申请中，我们建议 无神经/肌肉中枢神经系统功能改变所致动物(猫)模型的建立 损伤，揭示了FDA批准的唯一治疗方法--骶神经调节的可能机制，以及 开发新的非侵入性神经调节疗法，将使更多的患者受益于有创的骶骨 神经调节疗法。

Project Summary A recent AUA white paper defines urinary retention as an elevated post-void residual (PVR) of >300 mL that persists for at least 6 months and is documented on 2 or more separate occasions. Although urinary retention caused by urethral outlet obstruction can be resolved by surgical or pharmacological treatment, non- obstructive urinary retention (NOUR) presents a significant therapeutic challenge to many clinicians. Currently an effective drug for NOUR does not exist. Sacral neuromodulation is the only FDA-approved therapy for NOUR. It can achieve >50% improvement (increasing voided volume, reducing the PVR and frequency of self- catheterization) in about 70% of patients with a long-term (5-10 years) efficacy. Currently the mechanism of sacral neuromodulation is still unknown. Sacral neuromodulation is invasive requiring a well-trained surgeon to implant a stimulator and an electrode to stimulate the sacral S3 root. The invasiveness and surgeon requirement significantly limit the impact of sacral neuromodulation to only a small percentage of NOUR patients, leaving most patients totally depending on daily intermittent self-catheterization to empty the bladder. Intermittent self-catheterization causes frequent lower urinary tract infections. Therefore, there is a great need for basic science research to develop new therapies for NOUR. However, currently very few studies focus on NOUR, which is in dramatic contrast to the extensive research in the literature focusing on overactive bladder (OAB). NOUR can be myogenic (caused by detrusor disease/damage), neurogenic (caused by neural disease/damage), or idiopathic (without an identifiable cause). Clinically, idiopathic NOUR without identifiable neural/muscle disease/damage includes many patients with un-identified functional changes in the CNS. Although myogenic or neurogenic animal models can be produced by bladder ischemia or pelvic nerve injury, it is very difficult to produce an animal model of NOUR without neural/muscle damage but caused by un- identified functional changes in the CNS (i.e. idiopathic model). Therefore, in this grant application we propose to build animal (cat) models of NOUR caused by functional changes in the CNS with no neural/muscle damage, reveal the possible mechanisms of the only FDA-approved therapy - sacral neuromodulation, and develop novel non-invasive neuromodulation therapies that will benefit more patients than the invasive sacral neuromodulation therapy.