Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives

Abstract

Abbreviations & Acronyms BPS = bladder pain syndrome CCL2 = C-C motif ligand 2 CNS = central nervous system DMSO = dimethyl sulfoxide EAC = experimental autoimmune cystitis ESSIC = International Society for the Study of BPS FSS = functional somatic syndrome GAG = glycosaminoglycan IC = interstitial cystitis IFN-c = interferon-gamma IL = interleukin MC = mast cell NGF = nerve growth factor OVA = ovalbumin TCR = T-cell receptor TNF = tumor necrosis factor TLR = Toll-like receptor UCPPS = urological chronic pelvic pain syndrome UPK = uroplakin Upo = unpublished observation VEGF = vascular endothelial growth factor WAS = water avoidance stress Correspondence: Yoshiyuki Abstract: Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating B cells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a noninflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.

Clinical characterization of interstitial cystitis/bladder pain syndrome in women based on the presence or absence of Hunner lesions and glomerulations

“…In the present study, we explored the clinical characteristics of female should be the first key step in undertaking an overall view of the IC/BPS landscape and in improving patients' management. 6,12,13 Recent clinicopathological and genomic studies suggested that HL-IC is a distinct disease entity from other forms of IC/BPS. 6,8,[13][14][15] neuroimmune abnormalities and/or psychosocial problems.…”

“…6,12,13 Recent clinicopathological and genomic studies suggested that HL-IC is a distinct disease entity from other forms of IC/BPS. 6,8,[13][14][15] neuroimmune abnormalities and/or psychosocial problems. 6,14,[16][17][18] As well as other studies of various populations and ethnic groups, this study demonstrated that HL-IC patients show distinct bladder-centric clinical features in a Japanese female cohort.…”

“…6,8,[13][14][15] neuroimmune abnormalities and/or psychosocial problems. 6,14,[16][17][18] As well as other studies of various populations and ethnic groups, this study demonstrated that HL-IC patients show distinct bladder-centric clinical features in a Japanese female cohort. 12,19,20 The present study has several limitations.…”

“…4,5 Recent studies indicate that HL-IC is a distinct inflammatory disease with proven bladder pathology, whereas the other forms of IC/BPS are non-inflammatory disorders showing few changes in bladder histopathology. [6][7][8] In addition, a variety of clinical phenotyping of IC/BPS have been proposed. [9][10][11] However, no studies have established clinically relevant phenotyping for IC/BPS.…”

Clinical phenotyping linked treatment strategies in patients with bladder pain syndrome

“…Etiopathogenesis of this heterogeneous entity is quite variable and if there could be a method of grouping or classifying these patients based on clinical clues to the underlying etiopathogensis, then therapies specific to addressing these respective pathogenic mechanisms may be used with good results. 2 The objective of this study was to categorize patients of bladder pain syndrome on the basis of clinical clues towards the possible pathogenic process and apply specific modality for treatment of same.…”