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 #
5R01DK090006-03
Application #
8322838
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
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$186,731
Indirect Cost
$63,476
Name
University of Pittsburgh
Department
Urology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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
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; 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
Mally, Abhijith D; Matsuta, Yosuke; Zhang, Fan et al. (2013) Role of opioid and metabotropic glutamate 5 receptors in pudendal inhibition of bladder overactivity in cats. J Urol 189:1574-9
Matsuta, Yosuke; Schwen, Zeyad; Mally, Abhijith D et al. (2013) Effect of methysergide on pudendal inhibition of micturition reflex in cats. Exp Neurol 247:250-8
Matsuta, Yosuke; Mally, Abhijith D; Zhang, Fan et al. (2013) Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation. Am J Physiol Regul Integr Comp Physiol 305:R126-33
Schwen, Zeyad; Matsuta, Yosuke; Shen, Bing et al. (2013) Involvement of 5-HT3 receptors in pudendal inhibition of bladder overactivity in cats. Am J Physiol Renal Physiol 305:F663-71
Tai, Changfeng; Larson, Jeffrey A; Ogagan, P Dafe et al. (2012) Differential role of opioid receptors in tibial nerve inhibition of nociceptive and nonnociceptive bladder reflexes in cats. Am J Physiol Renal Physiol 302:F1090-7
Chen, Guoqing; Larson, Jeffrey A; Ogagan, P Dafe et al. (2012) Post-stimulation inhibitory effect on reflex bladder activity induced by activation of somatic afferent nerves in the foot. J Urol 187:338-43
Zhang, Fan; Mally, Abhijith D; Ogagan, P Dafe et al. (2012) Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats. Am J Physiol Renal Physiol 302:F1576-82

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