MP1-09 ASSOCIATION BETWEEN AGE-RELATED DETRUSOR UNDERACTIVITY AND DOWNREGULATION OF THE BIOLOGICAL CLOCK OF CONNEXIN 43-DERIVED GAP JUNCTIONS IN RAT BLADDERS

Abstract

INTRODUCTION AND OBJECTIVES: Various diseases can cause altered afferent autonomic sensitivity of bladder, including diabetes, neurologic or vascular lesions, multiple sclerosis, recurrent infection, interstitial cystitis, pelvic pain syndrome. In current urologic clinical practice, to study autonomic and sensory bladder neuropathy, clinicians still rely on patientsi?/2 self-reported bladder sensation during the filling phase of urodynamics. We developed and tested the efficacy of an implantable bladder device which, when combined with the Neurometeri?/2, can be used to assess fiber specific afferent bladder sensation in the mouse. METHODS: We developed an implantable bladder device that applies selective nerve fiber stimuli (250 Hz for small myelinated Ad fibers and 5 Hz for unmyelinated C fibers) to the bladder mucosa in the mouse to determine bladder current perception threshold (CPT) values. We performed 4 experiments in 64 C57BL/6J mice to examine the effects of our device on voiding habits, assess the interobserver reliability of the sensory perception threshold and determine the effects of intravesical administration of resiniferatoxin and lidocaine on the sensory perception threshold. RESULTS: Sensory perception threshold values obtained by 2 blinded, independent observers were not different from each other (p1⁄40.74382). CPT values obtained at the 2 stimulation frequencies remained constant for at least 6 days after device implantation. A significant increase in CPT values after resiniferatoxin instillation was noted at a stimulus frequency of 5 Hz (p1⁄40.01347), whereas intravesical lidocaine led to an immediate increase in CPT at 250 (p1⁄40.0003) and 5 Hz (p1⁄40.0001). The implantation led to an early decreased voided volume and increased frequency of voids at 4 days, although these parameters returned to close normal after 6 days. The implanted bladder histology reveals defect created by device and mild inflammatory changes in next areas. CONCLUSIONS: Assessment of bladder afferent sensation with our newly developed device is feasible in mice. It provides CPTs that appear to be fiber-type selective for autonomic bladder afferent nerves.