Assessment of Altered Function in Diabetic Bladder

DESCRIPTION (provided by applicant): Diabetic bladder dysfunction (DBD) or diabetic cystopathy is one of the most common and debilitating complications of diabetes mellitus (DM) affecting well over 50% of the patients with either type I or type II diabetes. DBD could affect both the filling and voiding function of the bladder leading to urinary incontinence, poor emptying, high post void residual, and urinary tract infection. Dysfunction of the autonomic nervous system (ANS) innervating the bladder is suspected to play a major role in pathogenesis of the DBD. Yet, no reliable diagnostic test exists to assist with the detection of disturbances in the ANS of the bladder. We aim to complete the development and testing of a product that will allow the laboratory scientists and clinicians to test the status of the afferent ANS of the bladder in the animals or human subjects. The Transurethral Afferent Autonomic Nerve Conduction Threshold (TUR-ACT) Device will incorporate use of a newly developed probe with a commercially available product (Neurometer, Neurotron, Inc.) in measuring the afferent Autonomic Nerve function in the bladder of animals and human. In the Phase I of this STTR application, we will a) test the feasibility of use of TUR-ACT Device to assess autonomic nerve conduction threshold of small fiber afferent pathways in the bladder of the diabetic and normal rats; and b) test the possible change of the CPT value in normal rat after placement of suprapubic tube (SPT) for conduct of cystometrogram (CMG), after intravesical administration capsaicin, a C-fiber neuro-selective inhibiting agent, and Ice-water. The long term goals of this proposal is to develop a user friendly measurement tool to enable the laboratory scientists and clinicians to assess the disturbances of the ANS affecting the lower urinary tract of animals and human with DBD. The scope and experiments of this proposal is fully responsive to RFA HD- 04-018, because it will provide development of a device that will help the investigators and clinicians in detection and/or assessment of early signs of autonomic dysfunction in bladder dysfunction, and availability of a quantitative tests of autonomic dysfunction that can readily be used in an outpatient setting; the stated goals of the RFA.