MMPC :: Pilot & Feasibility Program Application Abstract

Pilot & Feasibility Program Application Abstract

Assessment of Bladder Sensory Threshold in Diabetic Mice

Firouz Daneshgari (Cleveland, OH)

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 patients with either type I or type II DM. 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 the pathogenesis of DBD. Yet, no reliable diagnostic test exists to assist with the detection of disturbances in the ANS of the bladder. We aim to complete development and feasibility testing of a prototype of a device that, in conjunction with a commercially available stimulator, Neurometer® (Neurotron, Inc.), will allow laboratory scientists to test the status of the afferent ANS of the bladder in mice. The prototype of our device, named “Bladder Sensory Threshold electrode” (BeST), consists of a suprapubically implanted electrode that connects to the Neurometer® CPT/C and allows transmission of fiber-selective electrical stimuli from the Neurometer® CPT/C to the afferent ANS fibers present in the bladder wall. The Neurometer® CPT/C emits sinusoidal electrical stimuli at frequencies of 5 Hz, 250 Hz and 2000 Hz with a current intensity range of .01 to 9.99 milliamperes (mA) to selectively stimulate small unmyelinated (C), small myelinated (Ad) and large myelinated (Aß) fibers of the ANS, respectively. Use of the BeST with the Neurometer® CPT/C, therefore, will enable investigators to assess the status of the afferent sensory fibers of the bladder. We have recently developed and validated the device for use in rats. The support sought through this application will allow us to adapt the device for mice and perform further validation studies for its use in mice. The Specific Aims of this project are: SA#1- to assess the feasibility of measurement of bladder sensory threshold (BST) values in C57BL/6 mice. SA#2- to examine the specificity of BST values in mice. SA# 3- to examine the differences in BST values in early and late stages of streptozotocin-induced DM in mice. At the conclusion of this project, we will have completed testing and development of a patentable and potentially marketable device for use in assessment of ANS in the bladder of mice. The scope and experiments of this proposal are fully responsive to MMPC’s Pilot and Feasibility Grant Program, because the work will “develop new technologies or miniaturization of existing technologies for use in mice, develop applications of existing technologies used in other species for use in mice, and provide new tests to meet identifiable, outstanding needs necessary to phenotype mouse models of metabolic disease” (quoted from the text of the MMPC Pilot and Feasibility Program RFA).

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