Bladder Pain Syndrome Patients Research Articles

Bladder pain syndrome and sexual function: a systematic review and meta-analysis.

Bladder pain syndrome (BPS)/interstitial cystitis can adversely affect physical, mental, and sexual health. The aim of the systematic review is to compare sexual function between patients with BPS and healthy controls and to examine whether or not treatment of BPS improves sexual function. A literature search was conducted on Embase, Medline, and other databases. Studies comparing sexual function in BPS patients with healthy controls and before/after treatment were included. Where appropriate, data were pooled in a meta-analysis, using a random effects model and the standardised mean difference (SMD) was used for comparison. Out of 384 studies initially identified, 26 studies met the inclusion criteria for the systematic review and 11 for the meta-analysis. Six studies compared sexual function in BPS cases with healthy controls. All studies found that the Female Sexual Function Index (FSFI) was worse in BPS cases than in controls. Pooled data from 5 studies showed that the SMD was -1.02 (CI -1.64, -0.4) in total FSFI scores between the cases and controls, p=0.001. Further analysis showed better sexual function in all FSFI subdomains in healthy controls. Five studies compared sexual function in BPS patients before treatment with after treatment. Pooled data from 3 studies showed an overall improvement in total FSFI score after intravesical treatment: SMD=0.69 (CI 0.23, 1.14), p=0.003. Further analysis showed improvement in all subdomains. Our review suggests that sexual function might be worse in BPS patients than in the general population, but it seems to improve with intravesical BPS treatment.

Intravesical Injection of Abobotulinumtoxin-A in Patients with Bladder Pain Syndrome/Interstitial Cystitis.

This study aimed to evaluate retrospectively the outcomes of Abobotulinumtoxin-A (Dysport®) intravesical injection in refractory interstitial cystitis/ bladder pain syndrome patients to first- and second-line treatment. From March 2016 to 2021, 44 adult patients with bladder pain syndrome who were refractory to first- and second-line treatment were enrolled in our study. The Bladder Pain/Interstitial Cystitis Symptom Score questionnaire was filled out for every patient before and 1-3 months after intervention in addition to urodynamic evaluation. Patient satisfaction was evaluated using a scoring system that was defined as high or >80% improvement (highly satisfied), intermediate 40%-79% (intermediate satisfaction), and poor 0%-39% improvement. The mean age of our study population was 57 years, including 41 females and 3 males. The mean follow-up time was 9 months. According to the results of urodynamics, 68% of cases had low capacity, and detrusor overactivity, while 18% had only low capacity. In terms of the endpoint outcome, half of the patients (52%) had intermediate satisfaction, whereas 41% reported a good response. Only 3 cases had no response or felt (7%) any improvement after the intervention (poor response). The paired t-test analysis revealed that the mean Bladder Pain/Interstitial Cystitis Symptom Score was reduced after injection (P = .001). Our results showed the efficacy and safety of intravesical injections with Abobotulinumtoxin-A (Dysport®) in patients with interstitial cystitis/bladder pain syndrome. Further randomized controlled trials are recommended to investigate its superiority over placebo considering the need for anesthesia, the occurrence of local complications, risks of urinary retention, and a large post-void residual (PVR) volume.

The effect of the pandemic period on Bladder Pain Syndrome patients under amitriptyline treatment.

COVID-19 is a disease that may cause anxiety, depression, and stress. Bladder pain syndrome (BPS) is a disease in which stress and psychological factors might negatively affect its course. In this study, we aimed to examine the possible clinical aggregation of the pandemic period on BPS patients. A total of 35 BPS patients diagnosed between 2010 and 2018 were included. All patients were using medical treatment, and the follow-up period was at least 6 months. According to our clinical follow-up protocol, the BPS patients were given the King's Health Questionnaire (KHQ), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Overactive Bladder Form V8 (OAB-V8), and Visual Analog Score (VAS) in every visit. In the sixth month of the pandemic, the clinical course of the patients was questioned by telephone or video interview, and their treatment continuities were questioned. Information was received about the delays in their follow-up and the difficulties in accessing healthcare opportunities. The same questionnaires were filled out and compared with pre-pandemic scores. The mean age of the patients included in the study was 50.2 ± 13.32 (min:20, max:74), 11 were males and 24 were females. The mean follow-up periods were 71.8 ± 35.6 months. All questionnaire scores showed an increase compared to the pre-pandemic period. A statistically significant increase was detected during the pandemic in all sub-units of the KHQ. The VAS and OAB-V8 scores of 16 patients who requested hospital admission were significantly higher than before the pandemic. However, there was no statistically significant difference in the increase in VAS and OAB-V8 scores of the 19 patients who refused to come to the hospital. BPS patients have been negatively affected by the emotional effects of the COVID-19 pandemic. Due to the fear, stress, anxiety, and depression, the symptoms of BPS patients exacerbated, and the patients could not receive the necessary support due to a lack of regular follow-ups.

Current status of patient-reported outcome measures and other subjective assessment grading tools in bladder pain syndrome.

Bladder pain syndrome (BPS) is characterised by chronic pain in the bladder area accompanied by urgency and/or frequency without the presence of other confusable diseases. Owing to a lack of gold standard diagnostic tests and definitive cure it is paramount to define treatment goals and validated measurements of outcomes. Patient-reported outcome measures (PROMs) are validated questionnaires completed by patients that can help to reduce ambiguity in the BPS patient treatment pathway, but they are currently underutilised. We present to our knowledge the first summary and analysis of all available PROMs in BPS patients. Review and critical evaluation of all relevant BPS guidelines presented in English language and a systematic search for PubMed database articles relating to PROMs and subjective assessment grading tools in BPS, interstitial cystitis and chronic pelvic pain syndrome. The ideal PROMs for BPS should assess urinary symptoms, pain, quality of life and sexual health. There are five PROMs designed specifically for BPS patients. The most universally used and quoted is the O'Leary-Sant questionnaire followed by the Pelvic Pain and Urgency Score and the Wisconsin Interstitial Cystitis scale. However, there is no single PROM for BPS that is ideal, and for comprehensive assessment several questionnaires are often used simultaneously. Patient-reported outcome measures are a valuable tool for use in the long-term management of patients burdened with BPS. There are now several disease-specific PROMs in use that have their respective advantages and disadvantages. Their use should be encouraged in future research as well as continued efforts to develop new PROMs that can address current shortcomings.

Association of physical therapy techniques can improve pain and urinary symptoms outcomes in women with bladder pain syndrome. A randomized controlled trial.

ABSTRACTPurpose:to verify the effects of biofeedback (BF) and manual therapy (MT) associated with transcutaneous electrical nerve stimulation (TENS) or postural exercises (PE) in the treatment of bladder pain syndrome (BPS) in women regarding pain and urinary symptoms.Materials and Methods:a parallel-randomized controlled trial was conducted in BPS patients diagnosed according to NIH clinical criteria. Two specialized physiotherapists applied demographic and validated questionnaires of perineal and suprapubic pain (VAS), urinary symptoms and problems (ICSI and ICPI) and sexual function (FSFI) and a physical assessment was made to identify myofascial trigger points. Thirty-one women, mean age 51.8 ± 10.9 were randomized in three groups of treatment consisting of ten weekly sessions of BF and MT (Conventional group); BF, MT, and TENS (TENS group); and BF, MT, and PE (Postural group).Results:Postural group improved perineal and suprapubic pain after treatment (p<0.001 and p=0.001, respectively), and the suprapubic pain improvement remained persistent at 3 months of follow up (p=0.001). Postural group improved urinary symptoms and problems after treatment (p<0.001 and p=0.005, respectively) and during follow up (p<0.001 and p=0.001).Conclusions:Biofeedback and manual therapy associated with postural exercises showed a significant improvement in perineal and suprapubic pain and urinary symptoms after treatment and during follow-up. Both results suggest a possible role for the use of this physiotherapy technique to treat BPS patients. Longer follow-up and a larger number of patients are necessary to confirm these conclusions.

Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis

BackgroundInterstitial cystitis, or bladder pain syndrome (IC/BPS), is a chronic bladder disorder characterized by lower abdominal pain associated with the urinary bladder and accompanied by urinary frequency and urgency in the absence of identifiable causes. IC/PBS can be separated into the classic Hunner’s ulcerative type and the more prevalent non-ulcerative disease. Our aim was to unravel the biological processes and dysregulated cell signaling pathways leading to the bladder remodeling in non-ulcerative bladder pain syndrome (BPS) by studying the gene expression changes in the patients’ biopsies.MethodsWe performed paired microRNA (miRNA) and mRNA expression profiling in the bladder biopsies of BPS patients with non-Hunner interstitial cystitis phenotype, using comprehensive Next-generation sequencing (NGS) and studied the activated pathways and altered biological processes based on the global gene expression changes. Paired mRNA-miRNA transcriptome analysis delineated the regulatory role of the dysregulated miRNAs by identifying their targets in the disease-induced pathways.ResultsEIF2 Signaling and Regulation of eIF4 and p70S6K Signaling, activated in response to cellular stress, were among the most significantly regulated processes during BPS. Leukotriene Biosynthesis nociceptive pathway, important in inflammatory diseases and neuropathic pain, was also significantly activated. The biological processes identified using Gene Ontology over-representation analysis were clustered into six main functional groups: cell cycle regulation, chemotaxis of immune cells, muscle development, muscle contraction, remodeling of extracellular matrix and peripheral nervous system organization and development. Compared to the Hunner’s ulcerative type IC, activation of the immune pathways was modest in non-ulcerative BPS, limited to neutrophil chemotaxis and IFN-γ-mediated signaling. We identified 62 miRNAs, regulated and abundant in BPS and show that they target the mRNAs implicated in eIF2 signalling pathway.ConclusionsThe bladders of non-ulcerative BPS patients recruited in this study had alterations consistent with a strong cell proliferative response and an up-regulation of smooth muscle contractility, while the contribution of inflammatory processes was modest. Pathway analysis of the integrated mRNA-miRNA NGS dataset pinpointed important regulatory miRNAs whose dysregulation might contribute to the pathogenesis. Observed molecular changes in the peripheral nervous system organization and development indicate the potential role of local bladder innervation in the pain perceived in this type of BPS.

Prevalence of autoimmune disorders among bladder pain syndrome patients’ relatives

Purpose Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients’ genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. Materials and methods Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O’Leary–Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. Results 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O’Leary–Sant symptom score is not reliable in screening for new BPS cases. Conclusions Our study suggests that in BPS patients’ families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.

Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome.

Global consensus on the standardization of terminology for interstitial cystitis/bladder pain syndrome is lacking and is in the formative stages. The Workshop on Hunner lesion versus non-Hunner lesion at the 2018 International Consultation on Interstitial Cystitis Japan discussed prevalence, performance and outcome of endoscopy, the role of histopathology, and markers. A panel of experts reviewed the literature regarding Hunner lesion vs. non-Hunner lesion interstitial cystitis/bladder pain syndrome. The prevalence of Hunner lesion has been reported to be 5-57%. Older age and smaller anatomic bladder capacity were associated with Hunner lesions. Cystoscopy using local anesthesia is not adequate in diagnosing interstitial cystitis but is needed to rule out confusable diseases. Cystoscopy with hydrodistention and redistention of the bladder is considered standard. A Hunner lesion is visualized as a quite typical inflammatory reaction: a reddened mucosal area with small vessels radiating towards a central scar, splitting at distension, usually associated with a waterfall bleeding pattern. Biopsies from the inflamed area show inflammatory infiltrates, granulation tissue, detrusor mastocytosis, and fibrin deposits. Ablation of Hunner lesions includes transurethral resection of lesions, fulguration, laser ablation, and cortical steroid injections. Mast cell density is a somewhat controversial matter, described differently in different studies: marked increase in Hunner lesion vs. non-Hunner lesion in the majority of studies, no difference in a few. Nitric oxide appears to be a definitive marker in distinguishing Hunner lesion vs. non-Hunner lesion disease. Macrophage migration inhibitory factor is elevated in Hunner lesion patients. Increased level of urinary proinflammatory genes expression has also been found in Hunner lesion subjects. Hunner lesion patients are clinically and pathologically distinct from non-Hunner lesion bladder pain syndrome patients.

Urine Gene Expression Profiles in Bladder Pain Syndrome Patients Treated with Triamcinolone

BackgroundThe pathogenesis of bladder pain syndrome (BPS) remains incompletely defined, and there is no standard treatment for BPS as yet. ObjectiveTo gain detailed insight into the disease pathobiology of BPS through comparative gene expression analysis of urine from BPS patients versus control individuals and, furthermore, to determine the efficacy of triamcinolone treatment in BPS patients in terms of the gene expression profiles in urine. Design, setting, and participantsA prospective pilot study including 21 urine samples from patients with Hunner’s lesions (n=6) and controls (n=9) between January and August 2017. InterventionTriamcinolone treatment of BPS patients. Outcome measurements and statistical analysisUrine samples from BPS patients were collected before (pretreatment group) and 2 wk after triamcinolone treatment (post-treatment group). Gene expression of urine sediment was analyzed using RNA sequencing. Pathways and biological processes in which differentially expressed genes are involved were analyzed. Results and limitationsA total of 3745 genes were found to be differentially expressed between the three groups tested. Gene expression differences between controls and BPS samples (630 differentially expressed genes) were more pronounced than the differences between pre- and post-treatment BPS samples (197 differentially expressed genes). Gen Set Enrichment Analysis showed that differentially expressed genes in BPS patients (pretreatment), compared with controls, were enriched for some functional gene networks associated with several metabolic processes and ribosome biogenesis. The limited number of patients included may not accurately represent the BPS population. ConclusionsGene expression profiles of urine sediment are able to discriminate between BPS and control patients. Moreover, we show that triamcinolone induces changes in urine gene expression profiles. patient summaryIn this report, we looked at gene expression profiles of urine sediment from patients with Hunner’s lesions, before and after triamcinolone treatment, and control individuals. We found that urine gene expression profiles are able to discriminate Hunner’s lesions patients from controls. Furthermore, we report, for the first time, that triamcinolone treatment of patients with Hunner’s lesions induces changes in bladder gene expression profiles that can be observed in urine samples.

Validation of the Spanish version of the Bladder Pain/Interstitial Cystitis-Symptom Score (BPIC-SS) questionnaire. A useful tool for the diagnosis of bladder pain syndrome

ObjectivesValidation of the Spanish version of the Bladder Pain/Interstitial Cystitis-Symptom Score (BPIC-SS) questionnaire to evaluate its utility for the diagnosis of bladder pain syndrome (BPS) patients in the Female and Urodynamics Urology Functional Units in Spain. Material and methodsThe Spanish adaptation of the BPIC-SS questionnaire was evaluated in 243 BPS patients. EQ-5D-5L, patient perception of bladder condition (PPBC) and global impression questionnaire (CGI-S) were collected. Consistency, test-retest reliability in patients without clinical changes at 15 days, criterion validity and sensitivity to change were assessed in BPS patients with clinical changes at 6 months. The cut-off point for discriminating BPS patients from other similar pathologies (overactive bladder or other urinary pathologies) was analyzed using ROC curve. ResultsMean (SD) BPIC-SS score (0–38) was 16.2 (12.0) points. Cronbach's alpha was 0.92 and intraclass coefficient correlation (ICC) was 0.82, ranging from 0.5 to 0.9 per item. Convergent validity determined a Spearman correlation of 0.63 with PPBC and −0.40 with EQ-5D-5L Visual Analogue Scale (VAS) and the effect size obtained in patients who improved their clinical status was 1.9. A score greater than or equal to 12 points in the BPIC-SS has been established as the best cut-off point for the diagnosis of BPS (87.5% sensitivity and 91.9% specificity). ConclusionsThe Spanish version of the BPIC-SS is a valid and reliable instrument for the diagnosis and follow-up of patients with BPS in Spain.

Validación de la versión española del cuestionario Bladder Pain/Interstitial Cystitis-Symptom Score (BPIC-SS). Un instrumento útil para el diagnóstico del síndrome de dolor vesical

ObjectivesValidation of the Spanish version of the Bladder Pain/Interstitial Cystitis-Symptom Score (BPIC-SS) questionnaire to evaluate its utility for the diagnosis of Bladder Pain Syndrome (BPS) patients in the Female and Urodynamics Urology Functional Units in Spain. Material and methodsThe Spanish adaptation of the BPIC-SS questionnaire was evaluated in 243 BPS patients. EQ-5D-5L, Patient Perception of Bladder Condition (PPBC) and global impression questionnaire (CGI-S) were collected. Consistency, test-retest reliability in patients without clinical changes at 15 days, criterion validity and sensitivity to change were assessed in BPS patients with clinical changes at 6 months. The cut-off point for discriminating BPS patients from other similar pathologies (Hyperactive Bladder or other urinary pathologies) was analysed using ROC curve. ResultsMean (SD) BPIC-SS score (0-38) was 16.2 (12.0) points. Cronbach's alpha was 0.92 and intraclass coefficient correlation (ICC) was 0.82, ranging from 0.5-0.9 per item. Convergent validity determined a Spearman correlation of 0.63 with PPBC and –0.40 with EQ-5D-5L Visual Analogue Scale (VAS) and the effect size obtained in patients who improved their clinical status was 1.9. A score greater than or equal to 12 points in the BPIC-SS has been established as the best cut-off point for the diagnosis of BPS (87.5% sensitivity and 91.9% specificity). ConclusionsThe Spanish version of the BPIC-SS is a valid and reliable instrument for the diagnosis and follow-up of patients with BPS in Spain.

Effect of amitriptyline in treatment interstitial cystitis or bladder pain syndrome according to two criteria: Does ESSIC criteria change the response rate?

The European Society for the Study of Interstitial Cystitis (ESSIC) recommended that interstitial cystitis (IC) should be replaced by bladder pain syndrome (BPS), which focused more attention on the painful or discomfort feeling related to bladder and weakened the importance of cystoscopy in diagnosis process. Our study aimed to explore whether this alteration changed the treatment outcomes of amitriptyline and whether cystoscopy was meaningful for the treatment of this disease. We conducted a retrospective study including 25 IC patients fulfilled the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria and 42 BPS patients diagnosed according to ESSIC criteria. All the patients received amitriptyline with a self-uptitration protocol. We compared the response rates of two groups by a patient reported global response assessment after 3 months and reclassified all the 67 patients according to ESSIC criteria, the response rates of different BPS types were also assessed. There was no significant difference of response rate between IC patients (12/25, 48%) and BPS patients (19/42, 45.2%) according to different criteria (P = 0.337). The response rate of BPS type 1 (13/30, 43.3%) was similar to that of type 2 or 3 (18/37, 48.6%) (P = 0.664). ESSIC criteria did not decrease the response rate of amitriptyline treatment for BPS patients compared to IC patients with complaint of bladder pain or discomfort. Cystoscopy showed no predictive effect for the treatment outcome of amitriptyline.

Determination of urinary hexosamines for diagnosis of bladder pain syndrome

Bladder pain syndrome (BPS) is a chronic disease characterized by urgency, bladder pain, and frequency, and urinary glycosaminoglycans are thought to reflect bladder epithelial deficiency in BPS. Sensitive and specific evaluation of total urinary glycosaminoglycans may be useful for the clinical diagnosis of BPS and its treatment. A procedure for the simultaneous determination of glucosamine and galactosamine produced from urinary glycosaminoglycans has been performed in BPS patients and healthy subjects. The total content of urinary hexosamines in BPS patients significantly increased by ~130% with the increase in glucosamine greater than galactosamine. A significant increase in total hexosamines content and in particular in glucosamine belonging to urinary heparan sulfate was determined in BPS patients compared with controls. We propose HS and in particular its low-molecular mass fragments and glucosamine assay as useful markers for a biochemical diagnosis of BPS and for monitoring this syndrome.

The Bladder Pain/Interstitial Cystitis Symptom Score: Development, Validation, and Identification of a Cut Score

Background There is a need to develop a self-report measure that reliably identifies moderate to severe bladder pain syndrome (BPS) patients for inclusion into clinical trials to assess the efficacy of new BPS treatments. Objective To develop and validate a patient-reported symptom-based instrument, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), for clinical trial eligibility of BPS patients. Design, setting, and participants Stage 1: Qualitative concept elicitation (CE) interviews were conducted with BPS patients in France ( n = 12), Germany ( n = 12), and the United States (US) ( n = 20), and overactive bladder (OAB) ( n = 10) patients in the US for comparison. Stage 2: Cognitive debriefing (CD) interviews were performed with US BPS patients ( n = 20). Stage 3: An observational study with 99 BPS, 99 OAB, and 100 healthy participants in the US was used to perform item reduction, identify cut scores, and validate the measure. A cut score was defined using logistic regression and receiver operating characteristic curves. Psychometric properties, including test-retest reliability, were assessed. Measurements In addition to the BPIC-SS, the Pelvic Pain and Urgency/Frequency Patient Symptom Scale, the Interstitial Cystitis Symptom Index, a Clinician Global Impression of Severity, and a Patient Global Impression of Change were included in the observational study. Results and limitations In CE, reported symptoms were bladder pain, persistent urge to urinate, and high urinary frequency. In CD, 13 items were deleted, and 15 were retained. Based on validation analyses, qualitative findings, and clinical relevance, the instrument was reduced to eight items that had strong sensitivity (0.72) and specificity (0.86) with a cut score ≥19 to determine clinical trial inclusion. Psychometric properties were strong. Conclusions The BPIC-SS is a reliable, valid, and appropriate questionnaire to select BPS/interstitial cystitis patients for clinical trials.

Fine structural characterization of chondroitin sulfate in urine of bladder pain syndrome subjects

Urothelial glycosaminoglycans (GAGs) are decreased in bladder pain syndrome (BPS), and urinary GAGs are thought to reflect this deficiency. In previous researches, urine GAG levels were found increased, decreased, or similar between BPS and controls. Additionally, no study is available on the structure characterization of urinary chondroitin sulfate (CS) in BPS patients. CS in the urine of BPS-affected patients and controls has been determined by specific electrophoresis, along with total GAGs and heparan sulfate (HS) percentage, and CS disaccharides have been quantified by high-performance liquid chromatography. No significant differences were obtained for total amount of GAGs, absolute content of CS and HS, and their relative percentages. Moreover, no differences were observed for CS structure confirming similar urine CS composition in BPS subjects and controls. This study found no significant differences of BPS and control urine GAG levels and CS structure to allow use of these parameters as diagnostic markers for BPS diagnosis.

Bladder pain syndrome: do the different morphological and cystoscopic features correlate?

For the diagnosis of bladder pain syndrome (BPS), the International Society for the Study of Bladder Pain Syndrome (ESSIC) recommends a specific diagnostic work-up using cystoscopy with hydrodistension and bladder biopsies. This study evaluates the correlation between the histological findings in bladder biopsies handled following ESSIC recommendations, as well as the importance of the histological features in BPS compared with the cystoscopic findings. The study included 15 men and 93 women. All patients underwent cystoscopy with hydrodistension, and at least three deep biopsies including detrusor muscle were taken. For the cell count the Leder stain was used most frequently. A cut-off point of 28 mast cells/mm(2) was used for detrusor mastocytosis. Significant correlations were found between urothelial damage and inflammatory infiltrate (p < 0.001). Detrusor mastocytosis was significantly more elevated in biopsies with normal urinary epithelium (Tukey corrected p < 0.0001) than in biopsies where the urothelium was damaged. No other correlations were found between histological findings or between histological and cystoscopic findings. Both cystoscopy with hydrodistension and histology can be used to illustrate different pathophysiological mechanisms in patients with BPS. These results favour the use of both in the classification of BPS patients.

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.