Quantitative Studies in Urinary Bladder Sensation

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(PLEASE KEEP IN WORD, DO NOT PDF) ABSTRACT. Acute and chronic pains originating from the urinary bladder are common clinical entities affecting most females at some time in their lives, particularly as they get older. In an attempt to understand urinary bladder hypersensitivity in a translational manner, this ongoing research project has used rodents to define basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using urinary bladder distension (UBD)-evoked reflexes and primary/spinal/supraspinal neuronal responses as experimental endpoints, clinically relevant models of bladder hypersensitivity have been developed. The present application explores the effect of aging on a rodent model of bladder pain that utilized neonatal bladder inflammation (NBI) to evoke many of the phenotypic features of interstitial cystitis/bladder pain syndrome (IC/BPS) with an emphasis on known alterations in opioidergic and corticotrophin releasing factor receptor (CRFR)-related modulatory mechanisms. Three Specific Aims are proposed: Specific Aim #1: To contrast/compare the effect of aging in rats which experienced neonatal bladder inflammation (NBI) and their controls on reflex and neuronal responses to urinary bladder distension (UBD) and bladder histology. Specific Aim #2: To contrast/compare the role of endogenous opioid systems modulating reflex & neuronal responses to UBD in both young adult and aged rats which experienced NBI and their controls. Specific Aim #3: To contrast/compare the role of spinal CRF systems modulating reflex & neuronal responses to UBD in both young adult and aged rats which experienced NBI and their controls. The proposed studies in rodent model systems will give insight related to bladder sensation and how it is altered by aging while exploring novel therapeutics. An improved understanding of sensory processing related to urinary bladder sensory pathways and their modulation by secondary insults will result in an increased translation of basic science to therapeutics for bladder pain.