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.
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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Clemens, J. Q., Markossian, T. W., Meenan, R. T., O’Keeffe Rosetti, M. C. & Calhoun, E. A. Overlap of voiding symptoms, storage symptoms and pain in men and women. J. Urol. 178, 1354–1358 (2007).
Bogart, L. M., Berry, S. H. & Clemens, J. Q. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. J. Urol. 177, 450–456 (2007).
Schaeffer, A. J. Clinical practice. Chronic prostatitis and the chronic pelvic pain syndrome. N. Engl. J. Med. 355, 1690–1698 (2006).
Held, P. J., Hanno, P. M., Wein, A. J., Pauly, M. V. & Cahn, M. A. in Interstitial Cystitis (eds Hanno, P. M., Staskin, D. R., Krane, R. J. & Wein, A. J.) 29–48 (Springer-Verlag, 1990).
Berry, S. H. et al. Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J. Urol. 186, 540–544 (2011).
Suskind, A. M. et al. The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. J. Urol. 189, 141–145 (2013).
Daniels, N. A., Link, C. L., Barry, M. J. & McKinlay, J. B. Association between past urinary tract infections and current symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome. J. Natl Med. Assoc. 99, 509–516 (2007).
Clemens, J. Q. et al. The MAPP Research Network: a novel study of urologic chronic pelvic pain syndromes. BMC Urol. 14, 57 (2014).
Landis, J. R. et al. The MAPP Research Network: design, patient characterization and operations. BMC Urol. 14, 58 (2014).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01098279 (2014).
Lai, H. H. et al. Characterization of whole body pain in urological chronic pelvic pain syndrome at baseline: a MAPP Research Network study. J. Urol. 198, 622–631 (2017).
Krieger, J. N. et al. Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study. J. Urol. 193, 1254–1262 (2015).
Maurer, A. J., Lissounov, A., Knezevic, I., Candido, K. D. & Knezevic, N. N. Pain and sex hormones: a review of current understanding. Pain Manag. 6, 285–296 (2016).
Berry, S. H. et al. Development, validation and testing of an epidemiological case definition of interstitial cystitis/painful bladder syndrome. J. Urol. 183, 1848–1852 (2010).
Lai, H. H. et al. Painful bladder filling and painful urgency are distinct characteristics in men and women with urological chronic pelvic pain syndromes: a MAPP Research Network study. J. Urol. 194, 1634–1641 (2015).
Clemens, J. Q. et al. Validation of a modified National Institutes of Health chronic prostatitis symptom index to assess genitourinary pain in both men and women. Urology 74, 983–987 (2009).
Griffith, J. W. et al. Pain and urinary symptoms should not be combined into a single score: psychometric findings from the MAPP Research Network. J. Urol. 195, 949–954 (2016).
O’Leary, M. P. et al. The interstitial cystitis symptom index and problem index. Urology 49, 58–63 (1997).
Rothrock, N. E., Lutgendorf, S. K., Kreder, K. J., Ratliff, T. L. & Zimmerman, B. Daily stress and symptom exacerbation in interstitial cystitis patients. Urology 57, 122 (2001).
Sutcliffe, S. et al. Urological chronic pelvic pain syndrome flares and their impact: qualitative analysis in the MAPP network. Int. Urogynecol. J. 26, 1047–1060 (2015).
Sutcliffe, S. et al. Changes in symptoms during urologic chronic pelvic pain syndrome symptom flares: findings from one site of the MAPP Research Network. Neurourol. Urodyn. 34, 188–195 (2015).
Sutcliffe, S. et al. Urological chronic pelvic pain syndrome symptom flares: characterisation of the full range of flares at two sites in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int. 114, 916–925 (2014).
Webster, D. C. & Brennan, T. Self-care strategies used for acute attack of interstitial cystitis. Urol. Nurs. 15, 86–93 (1995).
Alexander, R. B. & Trissel, D. Chronic prostatitis: results of an Internet survey. Urology 48, 568–574 (1996).
Herati, A. S. et al. Effects of foods and beverages on the symptoms of chronic prostatitis/chronic pelvic pain syndrome. Urology 82, 1376–1380 (2013).
Shorter, B., Lesser, M., Moldwin, R. M. & Kushner, L. Effect of comestibles on symptoms of interstitial cystitis. J. Urol. 178, 145–152 (2007).
Maclure, M. & Mittleman, M. A. Should we use a case-crossover design? Annu. Rev. Public Health 21, 193–221 (2000).
Sutcliffe, S. et al. A case-crossover study of urological chronic pelvic pain syndrome flare triggers in the MAPP Research Network. J. Urol. 199, 1245–1251 (2018).
Tang, Y. R., Yang, W. W., Wang, Y. L. & Lin, L. Sex differences in the symptoms and psychological factors that influence quality of life in patients with irritable bowel syndrome. Eur. J. Gastroenterol. Hepatol. 24, 702–707 (2012).
Poeschla, B., Strachan, E., Dansie, E., Buchwald, D. S. & Afari, N. Chronic fatigue and personality: a twin study of causal pathways and shared liabilities. Ann. Behav. Med. 45, 289–298 (2013).
Aaseth, K. et al. Personality traits and psychological distress in persons with chronic tension-type headache. The Akershus study of chronic headache. Acta Neurol. Scand. 124, 375–382 (2011).
Naliboff, B. D. et al. Widespread psychosocial difficulties in men and women with urologic chronic pelvic pain syndromes: case-control findings from the multidisciplinary approach to the study of chronic pelvic pain research network. Urology 85, 1319–1327 (2015).
Naliboff, B. D. et al. Clinical and psychosocial predictors of urological chronic pelvic pain symptom change in 1 year: a prospective study from the MAPP Research Network. J. Urol. 198, 848–857 (2017).
Mordasini, L. et al. Chronic pelvic pain syndrome in men is associated with reduction of relative gray matter volume in the anterior cingulate cortex compared to healthy controls. J. Urol. 188, 2233–2237 (2012).
Farmer, M. A. et al. Brain functional and anatomical changes in chronic prostatitis/chronic pelvic pain syndrome. J. Urol. 186, 117–124 (2011).
Apkarian, A. V., Baliki, M. N. & Geha, P. Y. Towards a theory of chronic pain. Prog. Neurobiol. 87, 81–97 (2009).
Moisset, X. & Bouhassira, D. Brain imaging of neuropathic pain. Neuroimage 37 (Suppl. 1), S80–S88 (2007).
Tracey, I. & Mantyh, P. W. The cerebral signature for pain perception and its modulation. Neuron 55, 377–391 (2007).
Harris, R. E. & Clauw, D. J. How do we know that the pain in fibromyalgia is “real”. Curr. Pain Headache Rep. 10, 403–407 (2006).
Allsop, S. A. et al. The DABBEC phenotyping system: towards a mechanistic understanding of CP/CPPS. Nat. Rev. Urol. 8, 107–113 (2011).
Alger, J. R. et al. Multisite, multimodal neuroimaging of chronic urological pelvic pain: methodology of the MAPP Research Network. Neuroimage Clin. 12, 65–77 (2016).
Martucci, K. T. et al. The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network. Pain 156, 1755–1764 (2015).
Kairys, A. E. et al. Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome. J. Urol. 193, 131–137 (2015).
Farmer, M. A. et al. Brain white matter abnormalities in female interstitial cystitis/bladder pain syndrome: a MAPP network neuroimaging study. J. Urol. 194, 118–126 (2015).
Kilpatrick, L. A. et al. Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome. J. Urol. 192, 947–955 (2014).
Bagarinao, E. et al. Preliminary structural MRI based brain classification of chronic pelvic pain: a MAPP network study. Pain 155, 2502–2509 (2014).
Kutch, J. J. et al. Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: a MAPP: research network neuroimaging study. Neuroimage Clin. 8, 493–502 (2015).
Huang, L. et al. Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study. Pain 157, 2782–2791 (2016).
Woodworth, D. et al. Unique microstructural changes in the brain associated with urological chronic pelvic pain syndrome (UCPPS) revealed by diffusion tensor MRI, super-resolution track density imaging, and statistical parameter mapping: a MAPP network neuroimaging study. PLOS ONE 10, e0140250 (2015).
Kutch, J. J. et al. Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study. Pain 158, 1069–1082 (2017).
Asavasopon, S. et al. Cortical activation associated with muscle synergies of the human male pelvic floor. J. Neurosci. 34, 13811–13818 (2014).
Rana, M., Yani, M. S., Asavasopon, S., Fisher, B. E. & Kutch, J. J. Brain connectivity associated with muscle synergies in humans. J. Neurosci. 35, 14708–14716 (2015).
Griffiths, D., Tadic, S. D., Schaefer, W. & Resnick, N. M. Cerebral control of the bladder in normal and urge-incontinent women. Neuroimage 37, 1–7 (2007).
Tadic, S. D. et al. Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol. Urodyn. 31, 652–658 (2012).
Fowler, C. J., Griffiths, D. & de Groat, W. C. The neural control of micturition. Nat. Rev. Neurosci. 9, 453–466 (2008).
Mai, J. & Paxinos, G. (eds) The Human Nervous System (Elsevier Academic Press, 2012).
Kuhtz-Buschbeck, J. P. et al. Cortical representation of the urge to void: a functional magnetic resonance imaging study. J. Urol. 174, 1477–1481 (2005).
Turnbull, G. K., Hamdy, S., Aziz, Q., Singh, K. D. & Thompson, D. G. The cortical topography of human anorectal musculature. Gastroenterology 117, 32–39 (1999).
Harper, D. E. et al. Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: a MAPP Research Network study. Neuroimage Clin. 17, 570–578 (2018).
Kutch, J. J. et al. Brain signature and functional impact of centralized pain: a multidisciplinary approach to the study of chronic pelvic pain (MAPP) network study. Pain 158, 1979–1991 (2017).
Kleinhans, N. M., Yang, C. C., Strachan, E. D., Buchwald, D. S. & Maravilla, K. R. Alterations in connectivity on functional magnetic resonance imaging with provocation of lower urinary tract symptoms: a MAPP Research Network feasibility study of urological chronic pelvic pain syndromes. J. Urol. 195, 639–645 (2016).
Apkarian, A. V., Bushnell, M. C., Treede, R. D. & Zubieta, J. K. Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain 9, 463–484 (2005).
Gracely, R. H., Petzke, F., Wolf, J. M. & Clauw, D. J. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 46, 1333–1343 (2002).
Ablin, K. & Clauw, D. J. From fibrositis to functional somatic syndromes to a bell-shaped curve of pain and sensory sensitivity: evolution of a clinical construct. Rheum. Dis. Clin. North Am. 35, 233–251 (2009).
Fillingim, R. B. Individual differences in pain responses. Curr. Rheumatol. Rep. 7, 342–347 (2005).
Arendt-Nielsen, L. & Yarnitsky, D. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J. Pain 10, 556–572 (2009).
Harris, R. E. et al. Comparison of clinical and evoked pain measures in fibromyalgia. J. Pain 7, 521–527 (2006).
Kosek, E., Ekholm, J. & Hansson, P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain 68, 375–383 (1996).
Wilder-Smith, C. H. & Robert-Yap, J. Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome. World J. Gastroenterol. 13, 3699–3704 (2007).
Greenspan, J. D. et al. Pain sensitivity risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case control study. J. Pain 12, T61–T74 (2011).
Maixner, W., Fillingim, R., Booker, D. & Sigurdsson, A. Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain. Pain 63, 341–351 (1995).
Giesecke, T. et al. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 50, 613–623 (2004).
Clauw, D. J. et al. The relationship between fibromyalgia and interstitial cystitis. J. Psychiatr. Res. 31, 125–131 (1997).
Fitzgerald, M. P., Koch, D. & Senka, J. Visceral and cutaneous sensory testing in patients with painful bladder syndrome. Neurourol. Urodyn. 24, 627–632 (2005).
Lai, H. H., Gardner, V., Ness, T. J. & Gereau, R. W. 4th Segmental hyperalgesia to mechanical stimulus in interstitial cystitis/bladder pain syndrome: evidence of central sensitization. J. Urol. 191, 1294–1299 (2014).
Ness, T. J., Lloyd, L. K. & Fillingim, R. B. An endogenous pain control system is altered in subjects with interstitial cystitis. J. Urol. 191, 364–370 (2014).
Ness, T. J., Powell-Boone, T., Cannon, R., Lloyd, L. K. & Fillingim, R. B. Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis. J. Urol. 173, 1983–1987 (2005).
Harte, S. E. et al. Development and validation of a pressure-type automated quantitative sensory testing system for point-of-care pain assessment. Med. Biol. Eng. Comput. 51, 633–644 (2013).
Geisser, M. E. et al. A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls. J. Pain 9, 417–422 (2008).
As-Sanie, S. et al. Increased pressure pain sensitivity in women with chronic pelvic pain. Obstet. Gynecol. 122, 1047–1055 (2013).
Harte, S. E. et al. Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula. Pain 157, 1933–1945 (2016).
Dagher, A. et al. Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the multidisciplinary approach to the study of chronic pelvic pain (MAPP) Research Network. BJU Int. 120, 130–142 (2017).
Pontari, M. A., Hanno, P. M. & Ruggieri, M. R. Comparison of bladder blood flow in patients with and without interstitial cystitis. J. Urol. 162, 330–334 (1999).
Kawasaki, Y. et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat. Med. 14, 331–336 (2008).
Kiguchi, N. et al. Vascular endothelial growth factor signaling in injured nerves underlies peripheral sensitization in neuropathic pain. J. Neurochem. 129, 169–178 (2014).
Chakraborty, S., Kaur, S., Guha, S. & Batra, S. K. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim. Biophys. Acta 1826, 129–169 (2012).
Schrepf, A. et al. Inflammation and inflammatory control in interstitial cystitis/bladder pain syndrome: associations with painful symptoms. Pain 155, 1755–1761 (2014).
Brown, J., Wang, H., Hajishengallis, G. N. & Martin, M. TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J. Dent. Res. 90, 417–427 (2011).
Milligan, E. D. & Watkins, L. R. Pathological and protective roles of glia in chronic pain. Nat. Rev. Neurosci. 10, 23–36 (2009).
Schrepf, A. et al. Toll-like receptor 4 and comorbid pain in interstitial cystitis/bladder pain syndrome: a multidisciplinary approach to the study of chronic pelvic pain research network study. Brain Behav. Immun. 49, 66–74 (2015).
Eller-Smith, O. C., Nicol, A. L. & Christianson, J. A. Potential mechanisms underlying centralized pain and emerging therapeutic interventions. Front. Cell Neurosci. 12, 35 (2018).
Schrepf, A. et al. Inflammation and symptom change in interstitial cystitis or bladder pain syndrome: a multidisciplinary approach to the study of chronic pelvic pain research network study. Urology 90, 56–61 (2016).
Lv, H., Hung, C. S., Chaturvedi, K. S., Hooton, T. M. & Henderson, J. P. Development of an integrated metabolomic profiling approach for infectious diseases research. Analyst 136, 4752–4763 (2011).
Parker, K. S. et al. Urinary metabolomics identifies a molecular correlate of interstitial cystitis/bladder pain syndrome in a multidisciplinary approach to the study of chronic pelvic pain (MAPP) Research Network cohort. EBioMedicine 7, 167–174 (2016).
McLellan, L. K. & Hunstad, D. A. Urinary tract infection: pathogenesis and outlook. Trends Mol. Med. 22, 946–957 (2016).
Schaeffer, A. J., Matulewicz, R. S. & Klumpp, D. J. in Campbell-Walsh Urology (eds Wein, A. J., Kavoussi, L. R., Partin, A. W. & Peters, C. A.) 237–303 (Elsevier, 2016).
Whiteside, S. A., Razvi, H., Dave, S., Reid, G. & Burton, J. P. The microbiome of the urinary tract — a role beyond infection. Nat. Rev. Urol. 12, 81–90 (2015).
Schiffner, H. [The importance of documentation in emergency medicine]. Z. Arztl. Fortbild. (Jena) 83, 675–676 (1989).
Nickel, J. C., Shoskes, D. A. & Irvine-Bird, K. Prevalence and impact of bacteriuria and/or urinary tract infection in interstitial cystitis/painful bladder syndrome. Urology 76, 799–803 (2010).
Warren, J. W. et al. Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis. J. Urol. 163, 1685–1688 (2000).
Siddiqui, H., Nederbragt, A. J., Lagesen, K., Jeansson, S. L. & Jakobsen, K. S. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 11, 244 (2011).
Wolfe, A. J. et al. Evidence of uncultivated bacteria in the adult female bladder. J. Clin. Microbiol. 50, 1376–1383 (2012).
Siddiqui, H., Lagesen, K., Nederbragt, A. J., Jeansson, S. L. & Jakobsen, K. S. Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol. 12, 205 (2012).
Abernethy, M. G. et al. Urinary microbiome and cytokine levels in women with interstitial cystitis. Obstet. Gynecol. 129, 500–506 (2017).
Nickel, J. C. et al. Search for microorganisms in men with urologic chronic pelvic pain syndrome: a culture-independent analysis in the MAPP Research Network. J. Urol. 194, 127–135 (2015).
Nickel, J. C. et al. Assessment of the lower urinary tract microbiota during symptom flare in women with urologic chronic pelvic pain syndrome: a MAPP network study. J. Urol. 195, 356–362 (2016).
Ackerman, A. L. et al. Mp29-10 alterations in the urinary fungal mycobiome in patients with bladder pain and urinary urgency. J. Urol. 197, e383–e384 (2017).
Lai, H. et al. Animal models of urologic chronic pelvic pain syndromes: findings from the multidisciplinary approach to the study of chronic pelvic pain research network. Urology 85, 1454–1465 (2015).
Lai, H. H. et al. Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder. Pain 152, 2117–2124 (2011).
Xu, S. et al. Transgenic mice expressing MCP-1 by the urothelium demonstrate bladder hypersensitivity, pelvic pain and voiding dysfunction: a multidisciplinary approach to the study of chronic pelvic pain research network animal model study. PLOS ONE 11, e0163829 (2016).
Rudick, C. N. et al. Host-pathogen interactions mediating pain of urinary tract infection. J. Infect. Dis. 201, 1240–1249 (2010).
Rosen, J. M. & Klumpp, D. J. Mechanisms of pain from urinary tract infection. Int. J. Urol. 21 (Suppl. 1), 26–32 (2014).
Rudick, C. N. et al. O-Antigen modulates infection-induced pain states. PLOS ONE 7, e41273 (2012).
Stemler, K. M. et al. Protamine sulfate induced bladder injury protects from distention induced bladder pain. J. Urol. 189, 343–351 (2013).
Crock, L. W. et al. Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain. J. Neurosci. 32, 14217–14226 (2012).
Crock, L. W. et al. Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception. Mol. Pain 8, 20 (2012).
Rudick, C. N., Chen, M. C., Mongiu, A. K. & Klumpp, D. J. Organ cross talk modulates pelvic pain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R1191–R1198 (2007).
Kim, R., Liu, W., Chen, X., Kreder, K. J. & Luo, Y. Intravesical dimethyl sulfoxide inhibits acute and chronic bladder inflammation in transgenic experimental autoimmune cystitis models. J. Biomed. Biotechnol. 2011, 937061 (2011).
Williams, D. A. Cognitive - behavioral therapy in central sensitivity syndromes. Curr. Rheumatol. Rev. 12, 2–12 (2016).
Sant, G. R. et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J. Urol. 170, 810–815 (2003).
Foster, H. E. Jr. et al. Effect of amitriptyline on symptoms in treatment naive patients with interstitial cystitis/painful bladder syndrome. J. Urol. 183, 1853–1858 (2010).
Propert, K. J. et al. A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. J. Urol. 163, 1434–1439 (2000).
Pontari, M. A. et al. Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. Arch. Intern. Med. 170, 1586–1593 (2010).
Hanno, P. M. et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J. Urol. 185, 2162–2170 (2011).
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.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
MAPP Research Network public website: http://www.mappnetwork.org/
- 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).
Microorganisms that usually do not cause disease but can do so under certain circumstances (for example, via stimulation of the host immune system).