The etiology and natural history of urologic chronic pelvic pain syndromes (UCPPS) are not well understood. Along with other MAPP Research Network sites, the University of Iowa will perform a longitudinal, phenotyping study of UCPPS symptom patterns. Within this Trans-MAPP study, we will characterize the role of neuroinflammation and hypothalamic pituitary axis (HPA) dysregulation in UCPPS symptoms and symptom change. The central hypothesis of this work is that toll-like receptor (TLR)-4 activation and (HPA) dysregulation are key underlying features of UCPPS and will be associated with UCPPS symptom changes, flares and disease progression. To test this hypothesis, men and women with UCPPS will be enrolled into the 36-month Symptom Patterns Study, in which symptoms, symptom change and flare frequency and severity will be characterized (Aim 1). In-person and internet-based questionnaires will be collected every 3 months. Complementary Trans-MAPP research will determine the role of inflammatory biomarkers, and stress pathways with respect to urological and non-urological longitudinal symptom patterns and flares (Aim 2);develop, test and use a mobile application to provide real-time, ecological momentary assessments of pain and associated symptoms (Aim 3);perform brain magnetic resonance imaging to determine whether acute stress- evoked pain modulates brain networks and if changes in functional connectivity are predictive of long-term pain symptom change (Aim 4);and use preclinical UCPPS mouse models to determine whether TLR-2/TLR-4 sensitization is mechanistically linked to pain and voiding dysfunction (Aim 5). The work proposed will provide an integrated assessment of disease biomarkers, genetic predictors, real-time symptom measurement and brain structure/function in men and women with UCPPS and their associations with UCPPS symptom changes over time. In the animal model we will explore potential translational therapeutic approaches based on TLR-4 modulation. These Trans-MAPP study results will not only identify neuroinflammatory phenotypes related to symptom improvement, worsening, and flares but will also reveal mechanisms by which targeted UCPPS therapy may eventually be implemented.

Public Health Relevance

Results from this project will help us better understand how pain and urinary symptoms of Urologic Chronic Pelvic Pain Syndromes (UCPPS) change over time and define how inflammation and hormonal systems in the body may impact or predict UCPPS symptom changes. Understanding the course of this disease will ultimately lead to better management for these patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Mullins, Christopher V
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University of Iowa
Schools of Medicine
Iowa City
United States
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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
Xu, Suming; Wang, Xu; Wang, Yaoqin et al. (2016) Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS One 11:e0163829
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
Schrepf, Andrew; O'Donnell, Michael A; Luo, Yi et al. (2016) Inflammation and Symptom Change in Interstitial Cystitis or Bladder Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study. Urology 90:56-61
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
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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