Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network

Abstract

Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS.

Fig. 1 |. The MAPP Research Network’s integrated approach to systemic UCPPS phenotyping.

The schematic depicts the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network’s novel and highly integrated approach to the study of urologic chronic pelvic pain syndrome (UCPPS). Numerous diverse clinical and biological variables and methods are used to characterize UCPPS in a systemic manner (that is, beyond the traditional sole focus on the urological system) through a common clinical study employed across discovery sites (Trans-MAPP Epidemiology and Phenotyping Study). Analyses that combine data from the study domains (urological, nonurological, psychosocial, neuroimaging, quantitative sensory testing, molecular phenotyping, microbiome and animal models) are yielding broad new insights into UCPPS. Such insights are expected to directly inform the development of future evidence-based clinical studies (clinical trials) and, ultimately, clinical management, as well as seed future research studies by introducing new investigators with diverse expertise to the study of UCPPS, generating new hypotheses and constructing an unprecedented data and sample resource. COPCs, chronic overlapping pain conditions.

Fig. 2 |. MAPP I data domains and protocol.

In the first phase of studies (MAPP I), the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network collected extensive data describing urologic chronic pelvic pain syndrome (UCPPS) phenotypes. The schematic depicts the various study domains, protocols and associated UCPPS animal models used in the Trans-MAPP Epidemiology and Phenotyping (Trans-MAPP EP) Study. The specific measures collected for each study domain are listed, as well as notations of the main methods and relevant biological samples used, where applicable. Both participants with UCPPS and control individuals were assessed in these broad domains at baseline, and participants with UCPPS were assessed longitudinally during a 12-month follow-up period. AUA SI, American Urologic Association Symptom Index; BPCQ, Beliefs in Pain Control Questionnaire; BPI/45, Brief Pain Inventory-45; CFS, chronic fatigue syndrome; CMED, current medications; CMSI, Complex Medical Symptoms Inventory; CTES, Childhood Traumatic Events Scale; DTI, diffusion tensor imaging; EIL-INF, Early In Life Infection History; Family Hx, family history of UCPPS; fMRI, functional MRI; FSFI, Female Sexual Function Index; GUPI, Genitourinary Pain Index; HADS, Hospital Anxiety and Depression Scale; IBS, irritable bowel syndrome; ICINDEX, Interstitial Cystitis Symptom and Problem Index; ICPI, Interstitial Cystitis Problem Index; ICSI, Interstitial Cystitis Symptom Index; IIEF, International Index of Erectile Function; IPIP, International Personality Item Pool; MASQ, Multiple Ability Self-Report Questionnaire; MAST, multimodal automated sensory testing; MED, medical history; M/F SEAR, Male/Female Self-Esteem and Relationship Questionnaire; PANAS, Positive and Negative Affect Schedule; PROMIS, Patient-Reported Outcomes Measurement Information System; QOL, quality of life; RICE, RAND Interstitial Cystitis Epidemiology survey; RTES, Recent Traumatic Events Scale; SF12, 12-item Short-Form Health Survey; Sym Q, MAPP Symptom Questionnaire; TMJ, temporomandibular joint; UWMSFS, University of Washington Male Sexual Function Survey.

Fig. 3 |. MAPP I convergent neuroimaging findings.

Locations in the brain of altered function (green; assessed using resting-state functional MRI), grey matter structure (red; assessed using T1-weighted MRI) and white matter structure (blue; assessed using diffusion tensor MRI) in participants with urologic chronic pelvic pain syndrome (UCPPS) compared with matched healthy control individuals are shown^,. We note particular overlap in the right posterior insula (part a), the medial sensorimotor areas (part b) and the brainstem and periaqueductal grey (PAG) (part c). MAPP, Multidisciplinary Approach to the Study of Chronic Pelvic Pain.