Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than 50% of females at some time in their lives. Some conditions are easy to treat, but others, such as interstitial cystitis (1C), are conditions of bladder hypersensitivity that have proven resistant to diagnosis and treatment. As demonstrated in recently published studies, the PI has examined subjects with 1C using quantitative sensory testing and found them to be hypersensitive to bladder distension and other deep tissue stimuli such as muscle pressure and ischemia. The PI of these human studies has sought to understand this urinary bladder hypersensitivity in a translational manner and so in rodents has defined basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using UBD-evoked reflexes as experimental endpoints, clinically-relevant models of bladder hypersensitivity were developed. Unfortunately, it is not known which models of bladder hypersensitivity have the greatest relevance to 1C. A critical next step in the development of model systems for translational research is to systematically test these rodent models of bladder hypersensitivity for similarity or dissimilarity to the selected disease process, 1C. In this competitive renewal the PI seeks to take this next step in translational research by concommitantly examining the effects of a non-pharmacologic, sensation-modifying manipulation known to alter the sensation of pain. Specifically, the proposal examines the effect of Heterotopic Noxious Conditioning Stimulus (HNCS) administration on sensations of humans with 1C and on reflex and neuronal responses in three mechanistically-different, rodent bladder hypersensitivity modelSi using these Aims:
Specific Aim #1 : To quantitatively compare the presence and magnitude of HNCS effects in human subjects with interstitial cystitis (1C) with matched controls.
Specific Aim #2 : To quantitatively contrast and compare the magnitude of HNCS effects in rat and murine models of bladder hypersensitivity with appropriate controls. The proposed studies examining HNCS-related effects in the 1C population and in rodent model systems by the same researcher will give insight into the comparability of models of bladder hypersensitivity with pathological processes and thereby increase the translation of basic science to therapeutics for pain. ? ? ?
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