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A New Look at Urological Chronic Pelvic Pain ...

To help better understand the underlying causes of the two most prominent chronic urological pain disorders–interstitial cystitis/ bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), in 2008 the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) established the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

The MAPP Research Network embraces a systemic– or whole–body–approach in the study of Urologic Chronic Pelvic Pain Syndrome (UCPPS). UCPPS is a term adopted by the network to encompass both IC/BPS and CP/CPPS, which are proposed as related based on their similar symptom profiles. In addition to moving beyond traditional bladder– and prostate-specific research directions, MAPP Network scientists are investigating potential relationships between UCPPS and other chronic conditions that are sometimes seen in IC/PBS and CP/CPPS patients, such as irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome.

The primary clinical research effort carried out during the MAPP Network’s the first 5-year project period (MAPP I) was a prospective cohort study, the Trans-MAPP Epidemiology/Phenotyping (EP) Study. From 12/14/2009 through 12/14/2012 1,039 men and women were enrolled, including persons with UCPPS (n=424); persons with other co-morbid illnesses, including fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome (n=200 for all conditions); and healthy controls (n=415). All study participants were extensively characterized (i.e., phenotyped) at baseline, and UCPPS participants were further assessed during an additional 12 month follow-up period.

Initial analyses of these data have identified a number of provocative findings. There are strong indications those certain subgroups of participants (albeit with small sample sizes) with urinary and non-urinary symptoms tend to improve over time; whereas other subgroups tend to worsen over time. These patterns of improving or worsening are deferentially expressed according to sex, subtype of bladder pain syndrome (BPS), and pain location (e.g., localized to the pelvic region vs pain reported in the pelvic region as well as other body sites).

The second phase of the MAPP Network is now coming to an end and was designed to conduct a prospective, observational study of men and women with UCPPS, referred to as the Trans-MAPP Symptom Patterns Study (SPS). This collaborative study was enriched with pre-defined subgroups and involved a longer follow-up in order to describe UCPPS symptom changes over time and associated changes in underlying biology. The Trans-MAPP SPS further investigates and expands upon clinical and biologic insights identified in MAPP I and examines the potential for classification of UCPPS patients into clinically meaningful sub-groups based on differing pathophysiological profiles and/or potential to respond to certain clinical interventions.

The highly multidisciplinary (i.e., scientists employing a variety of research approaches) MAPP Network includes researchers with clinical, epidemiological, and basic research expertise, all working collaboratively:

Clinical researchers bring experience treating patients
Epidemiological investigators study the occurrence of, and identify risk factors for, IC/PBS and CP/CPPS
Basic research scientists examine what’s happening on a cellular level

The MAPP Network includes multiple key focus areas, including:

Epidemiology of Disease
Phenotyping of Urological and Non-Urological symptoms
Neuroimaging / Neurobiology Studies
Identification of Biomarkers of Disease
Characterizations of Organ Cross-Talk / Pain Pathways

The MAPP Research Network is comprised of six Discovery Sites that recruited participants and conducted the research studies and two Core Sites that coordinate data collection, analyze tissue samples, and provide technical support. In addition, the network supports three non-recruiting Discovery Sites that are focused in specific research areas of interest. To further broaden the scope and investigator base beyond the Discovery and Core sites, the MAPP Network also fosters the incorporation of ancillary study sites tasked with the conduct of clinical, basic, and translational research performed in collaboration within the network.

By promoting novel and innovative research approaches, the MAPP Network aims to discover new and clinically relevant insights that may lead to improved treatment options and better patient care.

Network Key Areas of Focus

Epidemiology of Disease This area of research examines how and why participants develop disease and how their disease changes over time. It also examines genetic, behavioral/lifestyle, environmental, and other factors as contributors to disease.

Phenotyping of Urological Symptoms This area of research is charged with developing a “working definition” for urological chronic pelvic pain disorders to be used by MAPP Network scientists. They will also design the diagnostic path—or the series of tests and questions used to determine if a urological pain participant has IC/PBS or CP/CPPS and what the disease characteristics, including urological symptom profiles, are for participants (i.e., the phenotype). The definitions and scientific tools developed by this group will be used in all MAPP Network studies.

Non-Urological Phenotying This area of research examines disease characteristics, including symptoms, of participants with pain conditions not specific to urological systems (e.g., the bladder and prostate). The questionnaire data and other tests to assess participant characteristics (i.e., phenotype) across a number of conditions potentially found in association with IC/PBS and/or CP/CPPS, such as irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome, will also be used in all MAPP Network studies.

Neuroimaging / Neurobiology This area of research intends to look at brain structure and function (e.g., neuroimaging studies) to help diagnosis and define certain pain conditions. Types of neuroimaging tests include computed tomography, magnetic resonance imaging (MRI), and positron-emission tomography. In pelvic pain conditions, functional MRIs may be used to confirm symptoms in patients suffering from painful conditions.

Biomarkers of Disease This area of research intends to determine the "biomarkers" that will help describe the causes of pelvic pain syndromes. Biomarkers are unique substances or features (e.g., proteins, genes, features of anatomy, etc) found in people with specific conditions that serve to identify the presence of diseases. Identification of biomarkers can help us diagnose and predict disease and may lead to a better understanding of the underlying causes of disease. Also, biomarkers can help physicians and researchers sub-group patients for more targeted treatments or research studies.

Characterization of UCPPS Translational Animal ModelsThis area of research intends to examine the interactions of various organs and pain pathways in order to help describe the causes and symptoms of pelvic pain syndromes, including how disease in one organ can influence the health of another organ.

Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain