Overactive bladder (OAB) is defined by the International Continence Society as a syndrome characterized by urgency with or without urge incontinence, usually with frequency and nocturia. About 33.3 million adults suffer from OAB in United States. The overall prevalence of OAB was 16.9% in women and 16.2% in men. The impact of OAB on quality of life is psychological, social, and profound. Antimuscarinic drugs are the first-line pharmacotherapy. However, many OAB patients withdraw from antimuscarinic treatment within 6-12 months due to its moderate efficacy and significant adverse effects such as dry mouth, constipation, headache, and blurred vision. Sacral neuromodulation is another treatment option, which is only offered to OAB patients after pharmacotherapy failed. However, the clinical benefit of sacral neuromodulation is significantly limited by its invasiveness, cost, and the requirement for well-trained surgeons. Currently it remains as a therapeutic challenge for clinicians to successfully treat OAB. The goal of this grant application is to develop new strategies to meet this therapeutic challenge. We hypothesize that combination of electrical and pharmacological neuromodulation can significantly improve the efficacy of current treatments for OAB, and create new, effective, non-invasive treatments acceptable for more patients. The first specific aim is to determine the efficacy of combined electrical and pharmacological neuromodulation. The second specific aim is to develop effective, non-invasive neuromodulation methods. The innovation of this project lies in its combinatorial approach that utilizes both pharmacological and electrical neuromodulation to target multiple neurotransmitters/receptors in order to treat the multifactorial disease - OAB. The success of our project could create several new treatment strategies for OAB with high efficacy, less adverse effect, less invasiveness, easy management, and acceptable for more patients, especially for the elderly and children patients who can not tolerate the adverse effects of pharmacotherapy or invasive surgery of sacral neuromodulation. Our studies will significantly benefit millions of Americans suffering from OAB.
The impact of overactive bladder (OAB) on quality of life is psychological, social, and profound. Currently it remains as a therapeutic challenge for clinicians to successfully treat OAB. Our project could create several new treatment strategies for OAB with high efficacy, less adverse effect, less invasiveness, easy management, acceptable for more patients (elderly and children), and significantly benefit millions of Americans suffering from OAB.
|Zhang, Zhaocun; Lyon, Timothy D; Kadow, Brian T et al. (2016) Conduction block of mammalian myelinated nerve by local cooling to 15-30°C after a brief heating. J Neurophysiol 115:1436-45|
|Rogers, Marc J; Shen, Bing; Reese, Jeremy N et al. (2016) Role of glycine in nociceptive and non-nociceptive bladder reflexes and pudendal afferent inhibition of these reflexes in cats. Neurourol Urodyn 35:798-804|
|Lyon, Timothy D; Ferroni, Matthew C; Kadow, Brian T et al. (2016) Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats. Am J Physiol Regul Integr Comp Physiol 310:R366-74|
|Zhang, Zhaocun; Slater, Richard C; Ferroni, Matthew C et al. (2015) Role of µ, ?, and ? opioid receptors in tibial inhibition of bladder overactivity in cats. J Pharmacol Exp Ther 355:228-34|
|Reese, Jeremy N; Rogers, Marc J; Xiao, Zhiying et al. (2015) Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats. Am J Physiol Renal Physiol 308:F832-8|
|Ferroni, Matthew C; Slater, Rick C; Shen, Bing et al. (2015) Role of the brain stem in tibial inhibition of the micturition reflex in cats. Am J Physiol Renal Physiol 309:F242-50|
|Rogers, Marc J; Xiao, Zhiying; Shen, Bing et al. (2015) Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats. Am J Physiol Regul Integr Comp Physiol 308:R42-9|
|Reese, Jeremy; Xiao, Zhiying; Schwen, Zeyad et al. (2014) Effects of duloxetine and WAY100635 on pudendal inhibition of bladder overactivity in cats. J Pharmacol Exp Ther 349:402-7|
|Xiao, Zhiying; Reese, Jeremy; Schwen, Zeyad et al. (2014) Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats. Am J Physiol Renal Physiol 306:F781-9|
|Schwen, Zeyad; Matsuta, Yosuke; Shen, Bing et al. (2014) Combination of foot stimulation and tolterodine treatment eliminates bladder overactivity in cats. Neurourol Urodyn 33:1266-71|
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