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

Nature Reviews Urology volume 16, pages 187–200 (2019)Cite this article

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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.

Key points

  • In urologic chronic pelvic pain syndrome (UCPPS), urological pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately rather than as part of a composite score.

  • Participants with UCPPS who report pain beyond the pelvis have more severe UCPPS symptoms and more symptom flares than those with pelvic pain only.

  • Participants with UCPPS reported more psychosocial difficulties than pain-free healthy control individuals; poor psychosocial functioning in participants with UCPPS was associated with a low likelihood of symptom improvement over time.

  • UCPPS involves disturbances in brain-level sensorimotor systems regulating urine storage; these disturbances are powerful enough to produce differences not only in brain function but also in brain structure.

  • Different UCPPS symptom profiles are distinguishable by their biological correlates (for example, immune factors).

  • Quantitative sensory testing has revealed markedly higher pressure pain sensitivity in participants with UCPPS than in healthy control individuals; high sensitivity was associated with a low likelihood of UCPPS symptom improvement.

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Fig. 1: The MAPP Research Network’s integrated approach to systemic UCPPS phenotyping.
Fig. 2: MAPP I data domains and protocol.
Fig. 3: MAPP I convergent neuroimaging findings.

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Acknowledgements

Funding for the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH (grants DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, DK82316, DK103227, DK103260 and DK103271) with additional funding from the NIH Office of Research on Women’s Health (ORWH). The authors thank the Interstitial Cystitis Association (ICA) and Prostatitis Foundation (PF) for their continued support and to the MAPP Research Network advisers serving on our External Experts Panel (EEP), especially W. Bushman. Finally, the authors express their thanks to all the MAPP Research Network investigators and especially to the study participants for their dedication to this effort.

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Authors and Affiliations

  1. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    J. Quentin Clemens

  2. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Chris Mullins & Tamara Bavendam

  3. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Beverly Hills, CA, USA

    A. Lenore Ackerman

  4. Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Adrie van Bokhoven

  5. Division of Digestive Diseases, University of California, Los Angeles, CA, USA

    Benjamin M. Ellingson & Jason J. Kutch

  6. Departments of Anesthesiology and Medicine, University of Michigan, Ann Arbor, MI, USA

    Steven E. Harte

  7. Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA

    Jason J. Kutch

  8. Division of Urologic Surgery, Department of Surgery, and Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA

    H. Henry Lai

  9. Department of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University, Palo Alto, CA, USA

    Katherine T. Martucci

  10. The Arthur Smith Institute for Urology, Zucker School of Medicine at Hofstra-Northwell, Lake Success, NY, USA

    Robert Moldwin

  11. Departments of Medicine, Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, CA, USA

    Bruce D. Naliboff

  12. Department of Urology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

    Michel A. Pontari

  13. Division of Public Health Sciences, Department of Surgery, and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Siobhan Sutcliffe

  14. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, USA

    J. Richard Landis

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  1. J. Quentin Clemens
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on behalf of the MAPP Research Network Study Group

Contributions

J.Q.C. and J.J.K. researched data for the article. All authors made substantial contributions to discussion of the article contents. J.Q.C., C.M., A.L.A., A.v.B., B.M.E., S.E.H., J.J.K., H.H.L., K.T.M., R.M., B.D.N., M.A.P., S.S. and J.R.L. wrote the manuscript. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to J. Quentin Clemens.

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Related links

MAPP Research Network public website: http://www.mappnetwork.org/

Supplementary Information

Glossary

Chronic overlapping pain conditions

(COPCs). Chronic pain conditions that are known to commonly co-occur in the same patients (for example, urologic chronic pelvic pain syndrome, fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, vulvodynia, migraine headaches and temporomandibular joint disorders).

Centralized pain phenotype

A phenotype in patients with chronic pain in which pain has modified the way the central nervous system works such that they have increased sensitivity to stimuli that should hurt but also to normal stimuli (for example, touch, pressure and sounds).

Hunner’s lesions

Painful bladder lesions that are observed in <10% of patients with interstitial cystitis/bladder pain syndrome; treatment of these lesions (cautery or steroid injection) often results in symptom relief of variable duration.

Ecological momentary assessment

A research approach that involves assessment of an individual’s experiences, behaviours and moods in real time and in their natural environment.

T1-weighted imaging

A type of human MRI that highlights the structure of grey matter in the brain (the location of neuronal cell bodies).

Diffusion tensor imaging

(DTI). A type of human brain MRI that highlights the structure of white matter (the location of axonal tracts).

Resting-state fMRI

(rs-fMRI). A type of human brain MRI that highlights activity within and interactions among grey matter regions during the awake resting state.

Mechanical allodynia

Also known as tactile allodynia. A painful sensation caused by innocuous stimuli such as light touch; pain originating from a visceral organ (bladder) is ‘referred’ (‘referred mechanical allodynia’) to a corresponding dermatome on the skin that shares spinal innervation with the specific visceral organ (suprapubic region).

Pathobionts

Microorganisms that usually do not cause disease but can do so under certain circumstances (for example, via stimulation of the host immune system).

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Clemens, J.Q., Mullins, C., Ackerman, A.L. et al. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol 16, 187–200 (2019). https://doi.org/10.1038/s41585-018-0135-5

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