The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network was established to focus on a broader approach to the study of Interstitial Cystitis (IC)/Painful Bladder Syndrome (PBS) in men and women, and Chronic Prostatitis (CP)/Chronic Pelvic Pain Syndrome (CPPS) in men. These conditions are often grouped using the research definition Urologic Chronic Pelvic Pain Syndrome (UCPPS) in many MAPP Network studies.

Participants with some form or symptoms of UCPPS were asked to join the MAPP Network’s Phase I Trans-MAPP Epidemiology and Phenotyping (EP) Study. Participants with no UCPPS symptoms as well as participants with specific conditions (Fibromyalgia (FM), Irritable Bowel Syndrome (IBS), Chronic Fatigue Syndrome (CFS)) were recruited for the Trans-MAPP Control Study, as “Healthy Controls” and “Positive Controls,” respectively. These participants were reference groups for the Trans-MAPP EP Study.

The Pelvic Pain Twin Study was a small, pilot study conducted at one MAPP Network Discovery site during MAPP Phase I using a unique sample of female, community-based twins from the University of Washington Twin Registry. This effort represented a co-twin control study, with pairs that were discordant for IC/PBS and was designed to identify IC/PBS phenotypes, characterize pathological and physiological associations with IC/PBS, and describe the relationship between IC/PBS and related chronic overlapping pain conditions (COPCs). The study cohorts/targets included pairs of IC/PBS-discordant female twins and healthy-healthy twin pairs, and followed the clinical and biological characterization and biological specimen collection strategy outlined in the MAPP Phase I Trans-MAPP EP Study protocol.

The primary objectives were to:

· Assess within-pair differences in demographic characteristics, symptoms, clinical features, psychiatric symptoms, and psychosocial and functional status in female monozygotic (MZ) and dizygotic (DZ) IC/PBS-discordant twins

· Assess between-pair effects to examine the genetic and common environmental contributions to the association between IC/PBS-discordant MZ twin pairs with IC/PBS-discordant DZ and female control pairs

· Examine within-pair differences in physical and uro-neurological findings, pain sensitivity and indicators of central sensitization, neuroendocrine function, and neuroimaging findings in a selected sample of female MZ and DZ twins with IC/PBS symptoms and their pain-free control twins

· Ascertain between-pair effects to examine the genetic and common environmental contributions to the association between IC/PBS and neurobiological characteristics, by comparing female IC-discordant MZ twin pairs with IC/PBS-discordant DZ and female control pairs

Clinical and biological outcome measures are detailed in the MAPP Phase I Trans-MAPP EP Study protocol.

Individuals were eligible for inclusion in the study as IC/PBS participants if they reported a response of at least 1 on the pain, pressure, or discomfort scale; provided informed consent; and reported an unpleasant sensation of pain, pressure, or discomfort, perceived to be related to the bladder and/or pelvic region, associated with lower urinary tract symptoms for the majority of the time during any 3 months in the previous 6 months, or for the majority of the time during the most recent 3 months.

See the Trans-MAPP EP protocol for complete inclusion/exclusion details for IC/PBS participants, and the Trans-MAPP Control protocol for complete inclusion/exclusion criteria for non-IC/PBS individuals.

This study assessed 10 female twin pairs, including 5 monozygotic and 5 dizygotic twins, for a total of 20 participants who were discordant for UCPPS-like symptoms on screening. Prior to functional magnetic resonance imaging, each twin urinated to completion and then consumed 500 cc water. Each twin was scanned immediately and approximately 50 minutes after consumption. Time series were extracted and analyzed to assess differences in connectivity between symptomatic and asymptomatic twins before and after bladder distention. Group by condition interaction effects were found from the periaqueductal gray to the right cerebellum VIIIa, the amygdala, the right premotor cortex/supplementary motor area and the insular cortex, and between the amygdala and the frontal pole/medial orbital frontal cortex, the hypothalamus, the insular cortex, the thalamus, and the anterior cingulate cortex. These findings demonstrate that a noninvasive bladder distention protocol can detect differences in the processing of urinary sensation between twins discordant for lower urinary tract pain.

Additional analysis of study data and specimens from the Twin Study is ongoing.