Interstitial cystitis/painful bladder syndrome (IC/PBS) is a common chronic bladder syndrome characterized by bladder pain and discomfort (urgency) and increased frequency of urination. It is part of a larger group of chronic functional pain disorders, which also include such common disorders as irritable bowel syndrome (IBS) and fibromyalgia (FM). A common feature of these syndromes is that they are multifactorial and present clinically as a mosaic of biologic and psychologic phenotypes. Despite intense, largely target organ-based drug development efforts, existing treatments are unsatisfactory. The current proposal, co-directed by experienced, senior investigators from gastroenterology and urology builds on this interdisciplinary view and aims to characterize the interactions of biological and environmental vulnerability factors to shape behavioral and neurobiological endophenotypes, and ultimately clinical phenotypes in IC/PBS. The 3 Projects of the proposal address the following 3 areas: Project 1 is a targeted epidemiological project studying the impact of genetic markers, early life experiences and adult stress on IC/PBS symptoms and comorbid pain syndromes. Project 2 is a clinical/translational study in a small cohort of IC/PBS patients (and in a rodent model of early life and chronic stress) which aims at characterizing several neurobiological and behavioral endophenotypes, and identifying their relationship to gene polymorphisms. Project 3 is a basic science study in IC/PBS patients and in the same rodent stress model which aims at studying cellular and molecular consequences of altered noradrenergic/SNS signaling on the urothelium and spinal glial cells. These projects involve a wide range of epidemiological, psychophysiological, neurobiological and molecular techniques, performed by an interdisciplinary group of investigators ranging from Urology, Gastroenterology, Epidemiology and Neuroscience, who have access to an established infrastructure to study neurovisceral interactions, and who have extensive previous experience in the study of functional pain syndromes, including IBS and IC/PBS. The projects closely interact with each other, and project investigators have been interacting with a large group of researchers and affiliated institutions. By deconstructing the complex, symptom-based syndrome of IC/PBS into distinct, neurobiological and behavioral endophenotypes, we anticipate the identification of more rationale drug development targets, and ultimately the development of more effective therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK082370-03
Application #
7928809
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M1))
Program Officer
Mullins, Christopher V
Project Start
2008-09-15
Project End
2013-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
3
Fiscal Year
2010
Total Cost
$717,037
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Sutcliffe, Siobhan; Jemielita, Thomas; Lai, H Henry et al. (2018) A Case-Crossover Study of Urological Chronic Pelvic Pain Syndrome Flare Triggers in the MAPP Research Network. J Urol 199:1245-1251
Clemens, J Quentin; Stephens-Shields, Alisa; Naliboff, Bruce D et al. (2018) Correlates of Health Care Seeking Activities in Patients with Urological Chronic Pelvic Pain Syndromes: Findings from the MAPP Cohort. J Urol 200:136-140
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Naliboff, Bruce D; Stephens, Alisa J; Lai, H Henry et al. (2017) Clinical and Psychosocial Predictors of Urological Chronic Pelvic Pain Symptom Change in 1 Year: A Prospective Study from the MAPP Research Network. J Urol 198:848-857
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Wang, Zhuo; Chang, Harriet H; Gao, Yunliang et al. (2017) Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. PLoS One 12:e0182976
Kutch, Jason J; Ichesco, Eric; Hampson, Johnson P et al. (2017) Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study. Pain 158:1979-1991
Lai, H Henry; Jemielita, Thomas; Sutcliffe, Siobhan et al. (2017) Characterization of Whole Body Pain in Urological Chronic Pelvic Pain Syndrome at Baseline: A MAPP Research Network Study. J Urol 198:622-631
Dagher, Adelle; Curatolo, Adam; Sachdev, Monisha et al. (2017) Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int 120:130-142

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