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Neuromodulation for Non-Obstructive Urinary Retention (NOUR)

非梗阻性尿潴留 (NOUR) 的神经调节

基本信息

批准号：
9795503
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
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9795503
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

项目摘要

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.

项目总结