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OBJECTIVES:Limited research suggests commonalities between urologic chronic pelvic pain syndromes (UCPPS) and other non-urologic chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs. METHODS:As part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network, we examined 1,039 individuals with UCPPS (n=424), non-urologic COPCs (n=200), and healthy controls (n=415). Validated standardized measures were used to assess urological symptoms, non-urological pain symptoms, and psychosocial symptoms and traits. RESULTS:Participants with UCPPS had more urologic symptoms than non-urologic COPCs or healthy controls (P

ObjectiveTo evaluate the genetic and environmental relationship among prostatitis and other urological conditions, including benign prostatic hyperplasia (BPH) and prostate cancer (CaP), a classical twin design and biometric modeling was used. While prostatitis-characterized by pain and voiding symptoms, no clear etiology, and functional and quality of life impairments-co-occurs with other urinary conditions, the degree of shared overlapping etiologic processes among them remains unclear. We examined the contribution of genetic and environmental factors to these conditions and the etiology of their associations at the level of genetic and environmental influences.Methods4380 monozygotic and dizygotic male twin pairs from the Vietnam Era Twin Registry reported lifetime physician-diagnosed prostatitis (combined acute and chronic), bladder problems, enlarged prostate/BPH, and CaP. Multivariate biometrical modeling estimated the magnitude of genetic and environmental influences for each condition, as well as their genetic and environmental covariance. The common pathway model tested the assumption that covariation among these urinary conditions is determined by a single latent factor.ResultsOverall prevalence of prostatitis was 2.7%. Heritability estimates ranged from 19% for bladder problems to 42% for CaP. Significant shared environmental influences were present for CaP (12%), enlarged prostate/BPH (10%) but were smaller than genetic influences. A reduced one factor common pathway model provided the best fit, suggesting that covariation among the conditions is determined by a shared latent factor.ConclusionWe identified a common, genetically-influenced factor that accounts for much of the comorbidity among these 4 disease conditions. Nonshared environmental factors also make a significant contribution.

ObjectivesChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs.MethodsData from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations.ResultsThere were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome.ConclusionsCP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities.

PurposeSymptoms of urinary irritation, urgency, frequency and obstruction, known as lower urinary tract symptoms, are common in urological practice. However, little is known about the etiology or pathogenesis of lower urinary tract symptoms, especially the relative contributions of genetic and environmental factors to the development of these symptoms. We used a classic twin study design to examine the relative contributions of genetic and environmental factors to the occurrence of lower urinary tract symptoms in middle-aged men.Materials and methodsTwins were members of the Vietnam Era Twin Registry. We used a mail survey to collect data on lower urinary tract symptoms using the I-PSS (International Prostate Symptom Score) instrument. Twin correlations and biometric modeling were used to determine the relative genetic and environmental contributions to variance in I-PSS total score and individual items.ResultsParticipants were 1,002 monozygotic and 580 dizygotic middle-aged male twin pairs (mean age 50.2 years, SD 3.0). Nearly 25% of the sample had an I-PSS greater than 8, indicating at least moderate lower urinary tract symptoms. The heritability of the total I-PSS was 37% (95% CI 32-42). Heritability estimates ranged from 21% for nocturia to 40% for straining, with moderate heritability (34% to 36%) for urinary frequency and urgency.ConclusionsGenetic factors provide a moderate contribution (20% to 40%) to lower urinary tract symptoms in middle-aged men, suggesting that environmental factors may also contribute substantially to lower urinary tract symptoms. Future research is needed to define specific genetic and environmental mechanisms that underlie the development of these symptoms and conditions associated with lower urinary tract symptoms.

PurposeThe purpose of this study was to create symptom indexes, that is scores derived from questionnaires to accurately and efficiently measure symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urological chronic pelvic pain syndromes. We created these indexes empirically by investigating the structure of symptoms using exploratory factor analysis.Materials and methodsAs part of the MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network 424 participants completed questionnaires, including GUPI (Genitourinary Pain Index), ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index). Individual items from questionnaires about bladder and pain symptoms were evaluated by principal component and exploratory factor analyses to identify indexes with fewer questions to comprehensively quantify symptom severity. Additional analyses included correlating symptom indexes with symptoms of depression, which is a known comorbidity of patients with pelvic pain.Results and conclusionsExploratory factor analyses suggested that the 2 factors pain severity and urinary severity provided the best psychometric description of items in GUPI, ICSI and ICPI. These factors were used to create 2 symptom indexes for pain and urinary symptoms. Pain, but not urinary symptoms, was associated with symptoms of depression on multiple regression analysis, suggesting that these symptoms may impact patients with urological chronic pelvic pain syndromes differently (B ± SE for pain severity = 0.24 ± 0.04, 95% CI 0.16-0.32, β = 0.32, p

ObjectiveTo determine the extent, severity, and sex differences of psychosocial deficits in men and women with urologic chronic pelvic pain syndromes (UCPPS), which in the past have been considered separate bladder (interstitial cystitis-painful bladder syndrome) and prostate (chronic prostatitis-chronic pelvic pain syndrome) disorders. Evaluations of men and women separately suggest UCPPS is associated with increased anxiety and depression. However, studies directly testing deficits in broader psychosocial domains such as cognitive processes, intimate relationships, and trauma history, or tests of sex differences in the pattern of difficulties associated with UCPPS have not been performed.MethodsA total of 233 female and 191 male UCPPS patients and 235 female and 182 male healthy controls (HCs) were recruited from 6 academic medical centers in the United States and evaluated with a comprehensive battery of symptom, psychosocial, and illness impact measures. Primary comparisons of interest were between UCPPS patients and HCs and between men and women with UCPPS.ResultsIn addition to greater negative effect, male and female UCPPS patients show higher levels of current and lifetime stress, poorer illness coping, increased self-report of cognitive deficits, and more widespread pain symptoms compared with sex- and education-matched HCs. Similar problems were found in male and female UCPPS patients although female UCPPS patients showed increased self-report of childhood adversity and more widespread symptoms of pain and discomfort.ConclusionGiven the significance of psychosocial variables in prognosis and treatment of chronic pain conditions, the results add substantially to our understanding of the breath of difficulties associated with UCPPS and point to important areas for clinical assessment.

PurposeWe used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria.Materials and methodsSelf-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors.ResultsOf 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p < 0.001).ConclusionsNonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes.

BackgroundThe "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described.MethodsThe primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as "positive" controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended follow-up study for 161 of the UCPPS participants is ongoing.DiscussionThe MAPP Research Network represents a novel, comprehensive approach to the study of UCPPS, as well as other concomitant NUAS. Findings are expected to provide significant advances in understanding UCPPS pathophysiology that will ultimately inform future clinical trials and lead to improvements in patient care. Furthermore, the structure and methodologies developed by the MAPP Network provide the foundation upon which future studies of other urologic or non-urologic disorders can be based.Trial registrationClinicalTrials.gov identifier: NCT01098279 "Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)". http://clinicaltrials.gov/show/NCT01098279.