Review Article| Volume 50, ISSUE 1, P39-52, February 2023

Pathophysiology and Clinical Biomarkers in Interstitial Cystitis

  • John M. Masterson
    Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    Search for articles by this author
  • Peris R. Castañeda
    Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    Search for articles by this author
  • Jayoung Kim
    Corresponding author. Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8635 W 3rd St #930E, Los Angeles, CA 90048.
    Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Division of Cancer Biology and Therapeutics, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8635 W 3rd St #930E, Los Angeles, CA 90048, USA
    Search for articles by this author


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Urologic Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Berry S.H.
        • Elliott M.N.
        • Suttorp M.
        • et al.
        Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States.
        J Urol. 2011; 186: 540-544
        • Suskind A.M.
        • Berry S.H.
        • Ewing B.A.
        • 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. 2013; 189: 141-145
        • Liu B.
        • Su M.
        • Zhan H.
        • et al.
        Adding a sexual dysfunction domain to UPOINT system improves association with symptoms in women with interstitial cystitis and bladder pain syndrome.
        Urology. 2014; 84: 1308-1313
        • Cox A.
        Management of interstitial cystitis/bladder pain syndrome.
        Can Urol Assoc J. 2018; 12: S157-S160
        • Rabin C.
        • O'Leary A.
        • Neighbors C.
        • et al.
        Pain and depression experienced by women with interstitial cystitis.
        Women Health. 2000; 31: 67-81
        • Michael Y.L.
        • Kawachi I.
        • Stampfer M.J.
        • et al.
        Quality of life among women with interstitial cystitis.
        J Urol. 2000; 164: 423-427
        • Rothrock N.E.
        • Lutgendorf S.K.
        • Kreder K.J.
        • et al.
        Stress and symptoms in patients with interstitial cystitis: a life stress model.
        Urology. 2001; 57: 422-427
        • French L.M.
        • Bhambore N.
        Interstitial cystitis/painful bladder syndrome.
        Am Fam Physician. 2011; 83: 1175-1181
        • Hanno P.M.
        • Erickson D.
        • Moldwin R.
        • et al.
        Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.
        J Urol. 2015; 193: 1545-1553
        • Cox A.
        • Golda N.
        • Nadeau G.
        • et al.
        CUA guideline: Diagnosis and treatment of interstitial cystitis/bladder pain syndrome.
        Can Urol Assoc J. 2016; 10: E136-E155
        • Tincello D.G.
        • Walker A.C.
        Interstitial cystitis in the UK: results of a questionnaire survey of members of the Interstitial Cystitis Support Group.
        Eur J Obstet Gynecol Reprod Biol. 2005; 118: 91-95
        • Hanno P.
        • Dmochowski R.
        Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot.
        Neurourol Urodyn. 2009; 28: 274-286
        • Hanno P.M.
        • Landis J.R.
        • Matthews-Cook Y.
        • et al.
        The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study.
        J Urol. 1999; 161: 553-557
        • Buffington C.A.
        Comorbidity of interstitial cystitis with other unexplained clinical conditions.
        J Urol. 2004; 172: 1242-1248
        • Warren J.W.
        • Howard F.M.
        • Cross R.K.
        • et al.
        Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome.
        Urology. 2009; 73: 52-57
        • Warren J.W.
        • Brown V.
        • Jacobs S.
        • et al.
        Urinary tract infection and inflammation at onset of interstitial cystitis/painful bladder syndrome.
        Urology. 2008; 71: 1085-1090
        • Ratliff T.L.
        • Klutke C.G.
        • Hofmeister M.
        • et al.
        Role of the immune response in interstitial cystitis.
        Clin Immunol Immunopathol. 1995; 74: 209-216
        • Rourke W.
        • Khan S.A.
        • Ahmed K.
        • et al.
        Painful bladder syndrome/interstitial cystitis: aetiology, evaluation and management.
        Arch Ital Urol Androl. 2014; 86: 126-131
        • Engelhardt P.F.
        • Morakis N.
        • Daha L.K.
        • et al.
        Long-term results of intravesical hyaluronan therapy in bladder pain syndrome/interstitial cystitis.
        Int Urogynecol J. 2011; 22: 401-405
        • Daly D.M.
        • Collins V.M.
        • Chapple C.R.
        • et al.
        The afferent system and its role in lower urinary tract dysfunction.
        Curr Opin Urol. 2011; 21: 268-274
        • You S.
        • Yang W.
        • Anger J.T.
        • et al.
        'Omics' approaches to understanding interstitial cystitis/painful bladder syndrome/bladder pain syndrome.
        Int Neurourol J. 2012; 16: 159-168
        • Elbadawi A.
        Interstitial cystitis: a critique of current concepts with a new proposal for pathologic diagnosis and pathogenesis.
        Urology. 1997; 49: 14-40
        • Parsons C.L.
        • Hurst R.E.
        Decreased urinary uronic acid levels in individuals with interstitial cystitis.
        J Urol. 1990; 143: 690-693
        • Mulholland S.G.
        • Hanno P.
        • Parsons C.L.
        • et al.
        Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study.
        Urology. 1990; 35: 552-558
        • Hohlbrugger G.
        The vesical blood-urine barrier: a relevant and dynamic interface between renal function and nervous bladder control.
        J Urol. 1995; 154: 6-15
        • Hohlbrugger G.
        Leaky urothelium and/or vesical ischemia enable urinary potassium to cause idiopathic urgency/frequency syndrome and urge incontinence.
        Int Urogynecol J Pelvic Floor Dysfunct. 1996; 7: 242-255
        • Sant G.R.
        • Theoharides T.C.
        The role of the mast cell in interstitial cystitis.
        Urol Clin North Am. 1994; 21: 41-53
        • Frenz A.M.
        • Christmas T.J.
        • Pearce F.L.
        Does the mast cell have an intrinsic role in the pathogenesis of interstitial cystitis?.
        Agents Actions. 1994; : C14-C15
        • Sant G.R.
        • Kempuraj D.
        • Marchand J.E.
        • et al.
        The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis.
        Urology. 2007; 69: 34-40
        • Hohenfellner M.
        • Nunes L.
        • Schmidt R.A.
        • et al.
        Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis.
        J Urol. 1992; 147: 587-591
        • Lundeberg T.
        • Liedberg H.
        • Nordling L.
        • et al.
        Interstitial cystitis: correlation with nerve fibres, mast cells and histamine.
        Br J Urol. 1993; 71: 427-429
        • Theoharides T.C.
        • Cochrane D.E.
        Critical role of mast cells in inflammatory diseases and the effect of acute stress.
        J Neuroimmunol. 2004; 146: 1-12
        • Clemens J.Q.
        • Mullins C.
        • Ackerman A.L.
        • et al.
        Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.
        Nat Rev Urol. 2019; 16: 187-200
        • Lai H.H.
        • Jemielita T.
        • Sutcliffe S.
        • et al.
        Characterization of Whole Body Pain in Urological Chronic Pelvic Pain Syndrome at Baseline: A MAPP Research Network Study.
        J Urol. 2017; 198: 622-631
        • Landis J.R.
        • Williams D.A.
        • Lucia M.S.
        • et al.
        The MAPP research network: design, patient characterization and operations.
        BMC Urol. 2014; 14: 58
        • Griffith J.W.
        • Stephens-Shields A.J.
        • Hou X.
        • et al.
        Pain and Urinary Symptoms Should Not be Combined into a Single Score: Psychometric Findings from the MAPP Research Network.
        J Urol. 2016; 195: 949-954
        • Clemens J.Q.
        • Calhoun E.A.
        • Litwin M.S.
        • et al.
        Validation of a modified National Institutes of Health chronic prostatitis symptom index to assess genitourinary pain in both men and women.
        Urology. 2009; 74: 983-987
        • O'Leary M.P.
        • Sant G.R.
        • Fowler Jr., F.J.
        • et al.
        The interstitial cystitis symptom index and problem index.
        Urology. 1997; 49: 58-63
        • Krieger J.N.
        • Stephens A.J.
        • Landis J.R.
        • 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. 2015; 193: 1254-1262
        • Lai H.H.
        • Qiu C.S.
        • Crock L.W.
        • et al.
        Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
        Pain. 2011; 152: 2117-2124
        • Rudick C.N.
        • Jiang M.
        • Yaggie R.E.
        • et al.
        O-antigen modulates infection-induced pain states.
        PLoS One. 2012; 7: e41273
        • Sutcliffe S.
        • Bradley C.S.
        • Clemens J.Q.
        • et al.
        Urological chronic pelvic pain syndrome flares and their impact: qualitative analysis in the MAPP network.
        Int Urogynecol J. 2015; 26: 1047-1060
        • Sutcliffe S.
        • Colditz G.A.
        • Goodman M.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. 2014; 114: 916-925
        • Sutcliffe S.
        • Colditz G.A.
        • Pakpahan R.
        • et al.
        Changes in symptoms during urologic chronic pelvic pain syndrome symptom flares: findings from one site of the MAPP Research Network.
        Neurourol Urodyn. 2015; 34: 188-195
        • Friedlander J.I.
        • Shorter B.
        • Moldwin R.M.
        Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions.
        BJU Int. 2012; 109: 1584-1591
        • Marinkovic S.P.
        • Moldwin R.
        • Gillen L.M.
        • et al.
        The management of interstitial cystitis or painful bladder syndrome in women.
        BMJ. 2009; 339: b2707
        • Nguan C.
        • Franciosi L.G.
        • Butterfield N.N.
        • et al.
        A prospective, double-blind, randomized cross-over study evaluating changes in urinary pH for relieving the symptoms of interstitial cystitis.
        BJU Int. 2005; 95: 91-94
        • Bird E.T.
        • Parker B.D.
        • Kim H.S.
        • et al.
        Caffeine ingestion and lower urinary tract symptoms in healthy volunteers.
        Neurourol Urodyn. 2005; 24: 611-615
        • Jura Y.H.
        • Townsend M.K.
        • Curhan G.C.
        • et al.
        Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence.
        J Urol. 2011; 185: 1775-1780
        • Bassaly R.
        • Downes K.
        • Hart S.
        Dietary consumption triggers in interstitial cystitis/bladder pain syndrome patients.
        Female Pelvic Med Reconstr Surg. 2011; 17: 36-39
        • Shorter B.
        • Lesser M.
        • Moldwin R.M.
        • et al.
        Effect of comestibles on symptoms of interstitial cystitis.
        J Urol. 2007; 178: 145-152
        • Dagher A.
        • Curatolo A.
        • Sachdev M.
        • 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. 2017; 120: 130-142
        • Parker K.S.
        • Crowley J.R.
        • Stephens-Shields A.J.
        • 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. 2016; 7: 167-174
        • Schrepf A.
        • Bradley C.S.
        • O'Donnell M.
        • 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. 2015; 49: 66-74
        • Gillenwater J.Y.
        • Wein A.J.
        Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987.
        J Urol. 1988; 140: 203-206
        • Rosamilia A.
        • Igawa Y.
        • Higashi S.
        Pathology of interstitial cystitis.
        Int J Urol. 2003; 10: S11-S15
        • Bradley M.S.
        • Burke E.E.
        • Grenier C.
        • et al.
        A genome-scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome.
        Neurourol Urodyn. 2018; 37: 1485-1493
        • Goo Y.A.
        • Tsai Y.S.
        • Liu A.Y.
        • et al.
        Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome: a pilot study.
        Int Braz J Urol. 2010; 36: 464-478
        • Keay S.
        • Zhang C.O.
        • Marvel R.
        • et al.
        Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor: sensitive and specific urine markers for interstitial cystitis.
        Urology. 2001; 57: 104
        • Keay S.
        • Zhang C.O.
        • Trifillis A.L.
        • et al.
        Decreased 3H-thymidine incorporation by human bladder epithelial cells following exposure to urine from interstitial cystitis patients.
        J Urol. 1996; 156: 2073-2078
        • Keay S.
        • Warren J.W.
        A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair.
        Med Hypotheses. 1998; 51: 79-83
        • Keay S.
        • Zhang C.O.
        • Shoenfelt J.L.
        • et al.
        Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis.
        Urology. 2003; 61: 1278-1284
        • Kim J.
        • Freeman M.R.
        Antiproliferative factor signaling and interstitial cystitis/painful bladder syndrome.
        Int Neurourol J. 2011; 15: 184-191
        • Yang W.
        • Chung Y.G.
        • Kim Y.
        • et al.
        Quantitative proteomics identifies a beta-catenin network as an element of the signaling response to Frizzled-8 protein-related antiproliferative factor.
        Mol Cell Proteomics. 2011; 10 (M110 007492)
        • Kutch J.J.
        • Yani M.S.
        • Asavasopon S.
        • et al.
        Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.
        Neuroimage Clin. 2015; 8: 493-502
        • Martucci K.T.
        • Shirer W.R.
        • Bagarinao E.
        • 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. 2015; 156: 1755-1764
        • Lai H.H.
        • Krieger J.N.
        • Pontari M.A.
        • 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. 2015; 194: 1634-1641
        • Colaco M.
        • Koslov D.S.
        • Keys T.
        • et al.
        Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.
        J Urol. 2014; 192: 1123-1129
        • Plair A.
        • Evans R.J.
        • Langefeld C.D.
        • et al.
        Anesthetic Bladder Capacity is a Clinical Biomarker for Interstitial Cystitis/Bladder Pain Syndrome Subtypes.
        Urology. 2021; 158: 74-80
        • Schachar J.S.
        • Evans R.J.
        • Parks G.E.
        • et al.
        Histological evidence supports low anesthetic bladder capacity as a marker of a bladder-centric disease subtype in interstitial cystitis/bladder pain syndrome.
        Int Urogynecol J. 2019; 30: 1863-1870
        • Choi D.
        • Han J.Y.
        • Shin J.H.
        • et al.
        Downregulation of WNT11 is associated with bladder tissue fibrosis in patients with interstitial cystitis/bladder pain syndrome without Hunner lesion.
        Sci Rep. 2018; 8: 9782
        • Cho K.J.
        • Lee K.S.
        • Choi J.B.
        • et al.
        Changes in uroplakin expression in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome.
        Investig Clin Urol. 2020; 61: 304-309
        • Lee G.
        Uroplakins in the lower urinary tract.
        Int Neurourol J. 2011; 15: 4-12
        • Aboushwareb T.
        • Zhou G.
        • Deng F.M.
        • et al.
        Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice.
        Neurourol Urodyn. 2009; 28: 1028-1033
        • Hu P.
        • Deng F.M.
        • Liang F.X.
        • et al.
        Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux.
        J Cell Biol. 2000; 151: 961-972
        • Hu P.
        • Meyers S.
        • Liang F.X.
        • et al.
        Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability.
        Am J Physiol Ren Physiol. 2002; 283: F1200-F1207
        • Kaga K.
        • Inoue K.I.
        • Kaga M.
        • et al.
        Expression profile of urothelial transcription factors in bladder biopsies with interstitial cystitis.
        Int J Urol. 2017; 24: 632-638
        • Liu H.T.
        • Jiang Y.H.
        • Kuo H.C.
        Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology.
        Low Urin Tract Symptoms. 2015; 7: 102-107
        • Shie J.H.
        • Kuo H.C.
        Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome.
        BJU Int. 2011; 108: E136-E141
        • Shie J.H.
        • Liu H.T.
        • Kuo H.C.
        Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome.
        Urology. 2012; 79: 484 e7-13
        • Tonyali S.
        • Ates D.
        • Akbiyik F.
        • et al.
        Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis.
        Adv Clin Exp Med. 2018; 27: 159-163
        • Jiang Y.H.
        • Jhang J.F.
        • Hsu Y.H.
        • et al.
        Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.
        Am J Physiol Ren Physiol. 2020; 318: F1391-F1399
        • Jiang Y.H.
        • Jhang J.F.
        • Hsu Y.H.
        • et al.
        Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm.
        Sci Rep. 2021; 11: 914
        • Ma E.
        • Vetter J.
        • Bliss L.
        • et al.
        A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder.
        Am J Physiol Ren Physiol. 2016; 311: F28-F34
        • Vera P.L.
        • Preston D.M.
        • Moldwin R.M.
        • et al.
        Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients.
        Urology. 2018; 116: 55-62
        • Pang D.
        • Liao L.
        Abnormal functional connectivity within the prefrontal cortex in interstitial cystitis/bladder pain syndrome (IC/BPS): A pilot study using resting state functional near-infrared spectroscopy (rs-fNIRS).
        Neurourol Urodyn. 2021; 40: 1634-1642
        • Duan L.
        • Zhang Y.J.
        • Zhu C.Z.
        Quantitative comparison of resting-state functional connectivity derived from fNIRS and fMRI: a simultaneous recording study.
        Neuroimage. 2012; 60: 2008-2018
        • Cui X.
        • Bray S.
        • Bryant D.M.
        • et al.
        A quantitative comparison of NIRS and fMRI across multiple cognitive tasks.
        Neuroimage. 2011; 54: 2808-2821
        • Geng S.
        • Liu X.
        • Biswal B.B.
        • et al.
        Effect of Resting-State fNIRS Scanning Duration on Functional Brain Connectivity and Graph Theory Metrics of Brain Network.
        Front Neurosci. 2017; 11: 392
        • Nardos R.
        • Karstens L.
        • Carpenter S.
        • et al.
        Abnormal functional connectivity in women with urgency urinary incontinence: Can we predict disease presence and severity in individual women using Rs-fcMRI.
        Neurourol Urodyn. 2016; 35: 564-573
        • Zuo L.
        • Zhou Y.
        • Wang S.
        • et al.
        Abnormal Brain Functional Connectivity Strength in the Overactive Bladder Syndrome: A Resting-State fMRI Study.
        Urology. 2019; 131: 64-70
        • Li P.
        • Bracamontes J.
        • Katona B.W.
        • et al.
        Natural and enantiomeric etiocholanolone interact with distinct sites on the rat alpha1beta2gamma2L GABAA receptor.
        Mol Pharmacol. 2007; 71: 1582-1590
        • Wilmore D.W.
        Are the metabolic alterations associated with critical illness related to the hormonal environment?.
        Clin Nutr. 1986; 5: 9-19
        • Saha S.K.
        • Jeon T.I.
        • Jang S.B.
        • et al.
        Bioinformatics Approach for Identifying Novel Biomarkers and Their Signaling Pathways Involved in Interstitial Cystitis/Bladder Pain Syndrome with Hunner Lesion.
        J Clin Med. 2020; 9
        • Bosch P.C.
        A Randomized, Double-blind, Placebo-controlled Trial of Certolizumab Pegol in Women with Refractory Interstitial Cystitis/Bladder Pain Syndrome.
        Eur Urol. 2018; 74: 623-630
        • Iizuka M.
        • Wakamatsu E.
        • Tsuboi H.
        • et al.
        Pathogenic role of immune response to M3 muscarinic acetylcholine receptor in Sjogren's syndrome-like sialoadenitis.
        J Autoimmun. 2010; 35: 383-389
        • Wu H.
        • Su Q.X.
        • Zhang Z.Y.
        • et al.
        Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome.
        Int Braz J Urol. 2021; 47: 843-855
        • Russo R.C.
        • Garcia C.C.
        • Teixeira M.M.
        • et al.
        The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases.
        Expert Rev Clin Immunol. 2014; 10: 593-619
        • Jaenisch R.
        • Bird A.
        Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals.
        Nat Genet. 2003; 33: 245-254
        • Marentette J.O.
        • Hauser P.J.
        • Hurst R.E.
        • et al.
        Tryptase activation of immortalized human urothelial cell mitogen-activated protein kinase.
        PLoS One. 2013; 8: e69948
        • Shin C.M.
        • Kim N.
        • Jung Y.
        • et al.
        Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis.
        Cancer Sci. 2010; 101: 1337-1346
        • Jiang Y.H.
        • Kuo Y.C.
        • Jhang J.F.
        • et al.
        Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis.
        Sci Rep. 2020; 10: 15218
        • Peng C.H.
        • Jhang J.F.
        • Shie J.H.
        • et al.
        Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical OnabotulinumtoxinA injections combined with hydrodistention for patients with interstitial cystitis--clinical results and immunohistochemistry analysis.
        Urology. 2013; 82: 1452 e1-6
        • Shen Y.C.
        • Tyagi P.
        • Lee W.C.
        • et al.
        Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo.
        Sci Rep. 2021; 11: 7558
        • Peters K.M.
        • Jayabalan N.
        • Bui D.
        • et al.
        Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients.
        Low Urin Tract Symptoms. 2015; 7: 77-83