Interactive Mechanisms of Pelvic Pain

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Pelvic pain syndromes cause severe pelvic pain and morbidity and impact families and the economy. Patients with urologic chronic pelvic pain syndromes (UCPPS) often suffer co-morbid conditions, such as irritable bowel syndrome (IBS). Effective treatment of chronic pelvic pain is complicated by imprecise clinical diagnoses and incomplete mechanistic understanding of these diseases, individually or as systemic conditions. Thus, our central hypothesis for this MAPP proposal is that improved diagnoses of well-defined patient groups and understanding of pelvic pain mechanisms will lead to improved therapies. The MAPP initiative will examine UCPPS within the context of co-morbidities at the levels of patient phenotype, epidemiology, and basic science. In other chronic conditions, chronic pain can be induced by a peripheral insult. Neural mechanisms can result in sustained pain even after the initiating insult is resolved, but it is unknown whether UCPPS causes similar changes. We will apply state-of-the-art pain methodologies to characterization of pelvic pain conditions. Because UCPPS and IBS share many similarities, including overlapping pain localization and voiding dysfunction, we will focus on UCPPS and IBS and will regard these conditions collectively as syndromes of chronic pelvic pain (SCPP). We will study mechanisms of SCPP in three innovative and synergistic projects. In Project I, we identify novel brain biomarkers of SCPP by characterizing brain morphometry/activity and cognitive function. In Project II, we will exploit the NIH Roadmap initiative PROMIS to determine the prevalence of SCPP in a large cohort. Finally, in Project III, we dissect pelvic organ crosstalk and spinal cord integration mechanisms that mediate co-morbidities and sustained pain in SCPP murine models. By focusing on the bladder, prostate, and bowel, our studies will benefit equally digestive disease and kidney/urologic disease, the dual missions of NIDDK, and provide the critical foundation for targeted therapies for SCPP. KEY ABBREVIATIONS SCPP = Syndromes of Chronic Pelvic Pain UCPPS = Urological Chronic Pelvic Pain Syndromes IBS = Irritable Bowel Syndrome CP = Chronic Prostatitis