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白皮书将尿retention留为> 300毫升的升高后残留物（PVR） 持续至少6个月，并在2个或更多单独的场合记录。虽然保留率 由尿道出口阻塞引起的可以通过手术或药理治疗来解决 阻塞性泌尿率（NOR）对许多临床医生提出了重大的治疗挑战。现在 不存在一种有效的NOR药物。 s骨神经调节是唯一的FDA批准疗法 nour。它可以提高> 50％的改善（增加了无效的体积，降低了自我的PVR和频率 长期（5 - 10年）患者中约有70％的导管插入术）。目前的机制 s骨神经调节仍然未知。 s骨神经调节是侵入性的，需要训练有素的外科医生 植入刺激器和刺激s3根的电极。侵入性和外科医生 需求显着限制了s骨神经调节的影响仅为少数NOR 患者，使大多数患者完全取决于每天间歇性自导管以清空膀胱。 间歇性的自导入化导致频繁的下尿路感染。因此，有很大的需求 用于基础科学研究以开发新的NOR疗法。但是，目前很少有研究重点 Nour，与关注过度活跃的文献中的广泛研究形成鲜明对比 （OAB）。 NOR可以是肌源性的（由逆变器疾病/损害引起），神经源性（由神经引起 疾病/损害）或特发性（没有可识别的原因）。临床上，特发性nour无法识别 神经/肌肉疾病/损害包括许多中枢神经系统中未识别功能变化的患者。 尽管可以通过膀胱缺血或骨盆神经损伤产生肌原性或神经源性动物模型，但 在没有神经/肌肉损害的情况下生产动物模型很难 确定了中枢神经系统的功能变化（即特发性模型）。因此，在此赠款申请中，我们建议 建立由无神经/肌肉的中枢神经系统功能变化引起的动物（猫）模型 损坏，揭示了唯一的FDA批准疗法的可能机制 - s骨神经调节和 开发新型的非侵入性神经调节疗法，该疗法将使患者受益更多的患者 神经调节疗法。