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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK090006-04
Application #
8543717
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Bavendam, Tamara G
Project Start
2010-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$180,196
Indirect Cost
$61,255
Name
University of Pittsburgh
Department
Urology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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
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
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
Zhang, Zhaocun; Slater, Richard C; Ferroni, Matthew C et al. (2015) Role of µ, κ, and δ 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
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
Yang, Guangning; Wang, Jicheng; Shen, Bing et al. (2014) Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats. Neuromodulation 17:490-6; discussion 496
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
Xiao, Zhiying; Rogers, Marc J; Shen, Bing et al. (2014) Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats. Am J Physiol Renal Physiol 307:F673-9

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