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)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Mullins, Christopher V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code
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
Kogan, Paul; Xu, Suming; Wang, Yaoqin et al. (2018) Sub-noxious Intravesical Lipopolysaccharide Triggers Bladder Inflammation and Symptom Onset in A Transgenic Autoimmune Cystitis Model: A MAPP Network Animal Study. Sci Rep 8:6573
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
Schrepf, Andrew; Naliboff, Bruce; Williams, David A et al. (2018) Adverse Childhood Experiences and Symptoms of Urologic Chronic Pelvic Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study. Ann Behav Med 52:865-877
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
Kutch, Jason J; Labus, Jennifer S; Harris, Richard E et al. (2017) Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study. Pain 158:1069-1082
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
Wang, Xu; Liu, Wujiang; O'Donnell, Michael et al. (2016) Evidence for the Role of Mast Cells in Cystitis-Associated Lower Urinary Tract Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS One 11:e0168772

Showing the most recent 10 out of 38 publications