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. The pathology and etiology of OAB currently remain unknown. OAB has devastating psychological and social impacts on quality of life, but treatments for OAB are clinically challenging. Sacral neuromodulation is a FDA approved treatment for OAB. Currently it is only offered to OAB patients after pharmacotherapy has failed. In addition, clinical studies have showed that pudendal neuromodulation is superior to sacral neuromodulation. It successfully treated OAB patients who have failed sacral neuromodulation. Furthermore, recent multicenter clinical trials have indicated that tibial neuromodulation is also effective for OAB treatment. Although neuromodulation is an effective treatment for OAB, the mechanisms underlying neuromodulation (sacral, pudendal, or tibial) are still unknown leaving neuromodulation as a mysterious therapy. More surprisingly there is very limited effort in basic science research aimed at revealing the possible mechanisms underlying neuromdulation. In this project we propose to elucidate the mechanisms underlying neuromodulation of bladder overactivity by answering the following question: what neurotransmitter receptors are involved in the different types of neuromodulation (sacral, pudendal, or tibial)? It would be na?ve to believe that the different neuromodulation therapies utilize the same neurotransmitter mechanisms to achieve the therapeutic effects on OAB conditions. Identifying the neurotransmitters/receptors involved in different neuromodulation therapies will remove the mysteries around bladder neuromodulation and provide basic science evidences. It will also provide new pharmacological interventions to further improve the efficacy of neuromodulation therapy. Information about the neurotransmitter mechanisms underlying neuromodulation could also be useful in developing new drugs to treat OAB. Our studies will significantly benefit millions of Americans suffering from OAB.

Public Health Relevance

Overactive bladder (OAB) has devastating psychological and social impacts on quality of life, but treatments for OAB are clinically challenging. Neuromodulation is an effective OAB treatment but its mechanism of action is currently unknown. Our project will identify neurotransmitter receptors involved in neuromodulation, which can be used to improve the clinical outcomes of this therapy, provide new targets for drug development, and significantly benefit millions of Americans suffering from OAB.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (UGPP)
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Bavendam, Tamara G
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University of Pittsburgh
Schools of Medicine
United States
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Li, Xing; Uy, Jamie; Yu, Michelle et al. (2018) Sacral neuromodulation blocks pudendal inhibition of reflex bladder activity in cats: insight into the efficacy of sacral neuromodulation in Fowler's syndrome. Am J Physiol Regul Integr Comp Physiol 314:R34-R42
Yecies, Todd; Li, Shun; Zhang, Yan et al. (2018) Spinal interneuronal mechanisms underlying pudendal and tibial neuromodulation of bladder function in cats. Exp Neurol 308:100-110
Li, Shun; Li, Xing; Theisen, Katherine et al. (2018) Saphenous nerve stimulation normalizes bladder underactivity induced by tibial nerve stimulation in cats. Am J Physiol Renal Physiol 315:F247-F253
Theisen, Katherine; Browning, Jeffery; Li, Xing et al. (2018) Frequency Dependent Tibial Neuromodulation of Bladder Underactivity and Overactivity in Cats. Neuromodulation 21:700-706
Li, Shun; Theisen, Katherine; Browning, Jeffery et al. (2018) Bladder underactivity after prolonged stimulation of somatic afferent axons in the tibial nerve in cats. Neurourol Urodyn 37:2121-2127
Yu, Michelle; Uy, Jamie; Jiang, Xuewen et al. (2017) An excitatory reflex from the superficial peroneal nerve to the bladder in cats. Am J Physiol Renal Physiol 313:F1161-F1168
Fuller, Thomas W; Jiang, Xuewen; Bansal, Utsav et al. (2017) Sex difference in the contribution of GABAB receptors to tibial neuromodulation of bladder overactivity in cats. Am J Physiol Regul Integr Comp Physiol 312:R292-R300
Bandari, Jathin; Bansal, Utsav; Zhang, Zhaocun et al. (2017) Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats. Neuromodulation 20:81-87
Zhang, Zhaocun; Bandari, Jathin; Bansal, Utsav et al. (2017) Sacral neuromodulation of nociceptive bladder overactivity in cats. Neurourol Urodyn 36:1270-1277
Jiang, Xuewen; Yu, Michelle; Uy, Jamie et al. (2017) Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats. Am J Physiol Renal Physiol 312:F482-F488

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