Neuromodulation for Non-Obstructive Urinary Retention (NOUR)

非梗阻性尿潴留 (NOUR) 的神经调节

• 批准号: 10212376
• 负责人: Changfeng Tai
• 金额: $ 23.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212376
• 关键词: Afferent Pathways; Animal Model; Animals; Applications Grants; Basic Science; Bladder; Catheterization; Clinical; Complex; Disease; Electrodes; Exhibits; FDA approved; Felis catus; Frequencies; Future; Hour; Implant; Ischemia; Leg; Literature; Location; Lower urinary tract; Micturition Reflex; Modeling; Muscle; Myopathy; Nerve; Neurotransmitters; Obstruction; Operative Surgical Procedures; Overactive Bladder; Paper; Patients; Pelvis; Periodicity; Peripheral Nerves; Pharmacological Treatment; Plant Roots; Research; Residual state; Site; Skin; Structure of tibial nerve; Surface; Surgeon; Syndrome; Therapeutic; Training; Urethra; Urethral sphincter; Urinary Retention; Urinary tract infection; Woman; afferent nerve; clinical translation; foot; improved; nerve injury; neuroregulation; non-drug; novel; novel therapeutics; pre-clinical; relating to nervous system; somatic afferent nerve; spinal nerve posterior root; success

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.

项目摘要 最近的AUA白色论文将尿潴留定义为>300 mL的排尿后残留量（PVR）升高， 持续至少6个月，并记录在2个或更多单独的场合。虽然尿潴留 引起的尿道出口梗阻可以通过手术或药物治疗解决，非 阻塞性尿潴留（NOUR）对许多临床医生提出了重大的治疗挑战。目前 目前还没有治疗NOUR的有效药物。骶神经调节是FDA批准的唯一治疗 NOUR.它可以达到>50%的改善（增加排尿量，降低PVR和自我检查频率）。 导管插入术）在约70%的患者中具有长期（5-10年）疗效。目前， 骶神经调节仍然是未知的。骶神经调节是侵入性的，需要训练有素的外科医生 植入刺激器和电极以刺激骶3神经根。侵入性和外科医生 要求将骶神经调节的影响显著限制为仅占NOUR的一小部分 患者，使大多数患者完全依赖于每天间歇性自我导尿来排空膀胱。 间歇性自我导尿会导致频繁的下尿路感染。因此，非常需要 用于基础科学研究，为NOUR开发新的疗法。然而，目前很少有研究关注 NOUR，这与文献中关注膀胱过度活动症的广泛研究形成鲜明对比 （OAB）。NOUR可以是肌源性的（由逼尿肌疾病/损伤引起）、神经源性的（由神经性疾病/损伤引起）、神经源性的（由神经性疾病/损伤引起）或神经源性的（由神经性疾病/损伤引起）。 疾病/损伤），或特发性（没有可识别的原因）。在临床上，特发性NOUR无可识别的 神经/肌肉疾病/损伤包括许多在CNS中具有未确定的功能变化的患者。 虽然肌源性或神经源性动物模型可以通过膀胱缺血或骨盆神经损伤来产生，但其 很难产生没有神经/肌肉损伤但由非- 确定CNS中的功能变化（即特发性模型）。因此，在这项拨款申请中，我们建议 建立由CNS功能变化引起的NOUR动物（猫）模型，无神经/肌肉 损伤，揭示唯一FDA批准的治疗-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，使更多患者受益，而不是侵入性骶神经调节疗法。 神经调节疗法