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Mechanisms of Pelvic Pain Crosstalk

$323,534U01FY2010DKNIH

Northwestern University At Chicago, Evanston IL

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Abstract

Urologic chronic pelvic pain syndromes (UCPPS) cause major morbidity in both women and men. TJCPPS patients often suffer co-morbid conditions that include another pelvic pain condition, irritable bowel syndrome (IBS). In addition, it is well-documented that patients suffering interstitial cystitis/painful bladder syndrome (IC/PBS) can experience flaring of symptoms in association with consumption of specific foodstuffs, yet the mechanisms of co-morbidities and dietary influences on UCPPS are unknown. Neural signals from pelvic organs that mediate perceived pain are integrated in the spinal cord by summation mechanisms, yet how these summation mechanisms influence pelvic pain is also unknown We recently developed murine models that mimic UCPPS and have characterized pelvic pain behavior in these models. In a model of IC/PBS, the bowel can modulate bladder-associated pelvic pain, but the bowel does not exert a similar influence on prostate-associated pelvic pain. Therefore, we hypothesize that bladder-induced and prostate-induced pelvic pain are differentially subject to organ crosstalk due to distinct spinal cord summation of pain signals originating at the bladder, colon, or prostate. To test this hypothesis, we will pursue three aims. In Aim 1, we will quantify pain in UCPPS and IBS models and determine the magnitude of summation processes and organ crosstalk at the level of pelvic pain behavior. In Aim 2, we will determine the summation mechanisms in the spinal cord by using a novel, isolated sacral spinal cord preparation to characterize pain-mediating neural responses. In Aim 3, we will assess the efficacy of single and multi-modal therapies directed to the periphery or CNS for their capacity to disrupt pelvic pain behavior and pain-induced spinal cord activities. Thus, these studies will define the underlying mechanisms that mediate organ crosstalk in pelvic pain, thereby illuminating the basis of co-morbidities and dietary sensitivities in IC/PBS.

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