Neuromodulation for Non-Obstructive Urinary Retention (NOUR)

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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.