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 #
5U01DK082370-05
Application #
8334670
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M1))
Program Officer
Mullins, Christopher V
Project Start
2008-09-15
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$726,115
Indirect Cost
$324,886
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
Alger, Jeffry R; Ellingson, Benjamin M; Ashe-McNalley, Cody et al. (2016) Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network. Neuroimage Clin 12:65-77
Nickel, J Curtis; Stephens, Alisa; Landis, J Richard et al. (2016) Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study. J Urol 195:356-62
Stephens-Shields, Alisa J; Clemens, J Quentin; Jemielita, Thomas et al. (2016) Symptom Variability and Early Symptom Regression in the MAPP Study: A Prospective Study of Urological Chronic Pelvic Pain Syndrome. J Urol 196:1450-1455
Huang, Lejian; Kutch, Jason J; Ellingson, Benjamin M et al. (2016) Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study. Pain 157:2782-2791
Griffith, James W; Stephens-Shields, Alisa J; Hou, Xiaoling et al. (2016) Pain and Urinary Symptoms Should Not be Combined into a Single Score: Psychometric Findings from the MAPP Research Network. J Urol 195:949-54
Labus, Jennifer S; Naliboff, Bruce; Kilpatrick, Lisa et al. (2016) Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders. Neuroimage 124:1232-7
Kutch, Jason J; Tu, Frank F (2016) Altered brain connectivity in dysmenorrhea: pain modulation and the motor cortex. Pain 157:5-6
Naliboff, Bruce D; Stephens, Alisa J; Afari, Niloo et al. (2015) Widespread Psychosocial Difficulties in Men and Women With Urologic Chronic Pelvic Pain Syndromes: Case-control Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network. Urology 85:1319-27
Sutcliffe, Siobhan; Bradley, Catherine S; Clemens, James Quentin et al. (2015) Urological chronic pelvic pain syndrome flares and their impact: qualitative analysis in the MAPP network. Int Urogynecol J 26:1047-60
Martucci, Katherine T; Shirer, William R; Bagarinao, Epifanio et al. (2015) The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network. Pain 156:1755-64

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