Defining Molecular Treatment Targets for Bladder Pain Syndrome/Interstitial Cystitis: Uncovering Adhesion Molecules

Abstract

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating pain syndrome of unknown etiology that predominantly affects females. Clinically, BPS/IC presents in a wide spectrum where all patients report severe bladder pain together with one or more urinary tract symptoms. On bladder examination, some have normal-appearing bladders on cystoscopy, whereas others may have severely inflamed bladder walls with easily bleeding areas (glomerulations) and ulcerations (Hunner’s lesion). Thus, the reported prevalence of BPS/IC is also highly variable, between 0.06% and 30%. Nevertheless, it is rightly defined as a rare disease (ORPHA:37202). The aetiopathogenesis of BPS/IC remains largely unknown. Current treatment is mainly symptomatic and palliative, which certainly adds to the suffering of patients. BPS/IC is known to have a genetic component. However, the genes responsible are not defined yet. In addition to traditional genetic approaches, novel research methodologies involving bioinformatics are evaluated to elucidate the genetic basis of BPS/IC. This article aims to review the current evidence on the genetic basis of BPS/IC to determine the most promising targets for possible novel treatments.

Comprehensive transcriptome profiling of urothelial cells following TNFα stimulation in an in vitro interstitial cystitis/bladder pain syndrome model

“…The TNFα-induced inflammatory in vitro model recapitulates key observations found in the urinary bladders of individuals with IC/BPS, as shown in the present study. Several enriched pathways and processes, observed in the bladder of patients with IC/BPS, especially those with Hunner’s lesions, including complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, granulocyte chemotaxis and migration, inflammatory response, TLR-, NOD-like receptor-, NFkB-and TNF-signaling pathways ( 14 , 17 , 32 , 48 , 49 ) were also identified in our study. These data support the utility of TNFα-treated RT4 urothelial cells as a suitable in vitro model for understanding IC/BPS mechanisms and confirm the role of TNFα signaling as an important component in the associated pathology.…”

Gene Expression-Based Functional Differences between the Bladder Body and Trigonal Urothelium in Adolescent Female Patients with Micturition Dysfunction

“…However, despite molecular studies that have been conducted in BPS/IC, neither disease biomarkers which could aid in diagnosis nor potential targets for treatment have been identified yet [ 64 ]. Many aspects of BPS/IC, including pathophysiology, proper causative definitions as well as diagnostic and treatment criteria remain to be clarified [ 65 , 66 ]. Unfortunately, our study did not determine an association of molecular findings with clinical symptoms.…”