The lower urinary tract has two functions: urine storage and elimination. During storage, the bladder is relaxed while the urethra is closed by tonic contraction of the urethral sphincter. When the bladder is full, voiding occurs as a result of bladder contraction and simultaneous relaxation of the urethral sphincter. This coordination between bladder and urethra sphincter is normally controlled by a spinobulbospinal micturition reflex. However, after spinal cord injury (SCI) above the lumbar level the brain control is lost and spinal reflex mechanisms emerge, which produce both detrusor overactivity - bladder contracts frequently even at relatively small volumes, and detrusor sphincter dyssynergia - urethral sphincter and bladder contract simultaneously. These lower urinary tract dysfunctions have a tremendous impact on the quality of life in people with SCI. Current treatments have either limited success or troublesome side effects. The long-term goals of this project are to reveal the neural mechanisms contributing to neurogenic detrusor overactivity and to characterize several lower urinary tract reflexes that could be used to normalize voiding function in people with SCI. In order to determine the spinal mechanisms underlying the recovery of bladder-to-bladder and somato-to-bladder reflexes after SCI, we will employ spinal functional magnetic resonance imaging, electrophysiological, and immunocytochemical techniques to examine the spinal organization and properties of these reflexes in normal, acute and chronic SCI cats and the mechanism underlying the spinal interactions between somatic and parasympathetic afferent inputs. Previous studies in other labs and our preliminary studies have demonstrated that both inhibitory and excitatory somato-to-bladder reflexes can be induced in normal and SCI animals or humans depending on stimulation location and frequency. The neural circuitry and neurotransmitters involved in these inhibitory or excitatory somato-to-bladder reflexes will be studied with electrophysiological and pharmacological techniques. Understanding the neuroplasticity underlying functional changes of lower urinary tract reflexes after SCI, and revealing the neural pathways and neurotransmitters involved in these reflexes will not only improve our knowledge about micturition control, but will also stimulate the development of more effective treatments for people with SCI and improve the quality of life. ^

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
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Hoshizaki, Deborah K
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University of Pittsburgh
Schools of Medicine
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Yu, Yongbei; de Groat, William C (2013) Nitric oxide modulates bladder afferent nerve activity in the in vitro urinary bladder-pelvic nerve preparation from rats with cyclophosphamide induced cystitis. Brain Res 1490:83-94
de Groat, William C; Yoshimura, Naoki (2012) Plasticity in reflex pathways to the lower urinary tract following spinal cord injury. Exp Neurol 235:123-32
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
Tai, Changfeng; Guo, Dong; Wang, Jicheng et al. (2011) Mechanism of conduction block in amphibian myelinated axon induced by biphasic electrical current at ultra-high frequency. J Comput Neurosci 31:615-23
Tai, Changfeng; Shen, Bing; Chen, Mang et al. (2011) Suppression of bladder overactivity by activation of somatic afferent nerves in the foot. BJU Int 107:303-9
Tai, Changfeng; Shen, Bing; Chen, Mang et al. (2011) Prolonged poststimulation inhibition of bladder activity induced by tibial nerve stimulation in cats. Am J Physiol Renal Physiol 300:F385-92
Tai, Changfeng; Chen, Mang; Shen, Bing et al. (2011) Irritation induced bladder overactivity is suppressed by tibial nerve stimulation in cats. J Urol 186:326-30
Kanai, Anthony; Zabbarova, Irina; Ikeda, Youko et al. (2011) Sophisticated models and methods for studying neurogenic bladder dysfunction. Neurourol Urodyn 30:658-67
Larson, Jeffrey A; Ogagan, P Dafe; Chen, Guoqing et al. (2011) Involvement of metabotropic glutamate receptor 5 in pudendal inhibition of nociceptive bladder activity in cats. J Physiol 589:5833-43
Tai, Changfeng; Chen, Mang; Shen, Bing et al. (2011) Plasticity of urinary bladder reflexes evoked by stimulation of pudendal afferent nerves after chronic spinal cord injury in cats. Exp Neurol 228:109-17

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