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PurposeInterstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer’s quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques.MethodsA comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about “Interstitial cystitis” and “Painful Bladder Syndrome”. Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey.ResultsThe etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no “gold standards” in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers.ConclusionDue to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

Interstitial cystitis/bladder pain syndrome (IC/BPS) causes significant discomfort in patients and impairs the quality of urination. Pterostilbene (PTE), a natural polyphenol antioxidant, has demonstrated beneficial effects in mitigating inflammation, enhancing antioxidant capacity, and ameliorating organ dysfunction in various chronic nonspecific inflammatory conditions. The aim of this study was to evaluate the efficacy of PTE in IC/BPS and elucidate its underlying mechanisms using a rat model of cyclophosphamide (CYP)-induced interstitial cystitis. In comparison, chronic pain progression, histopathological features, and cytokine levels demonstrated that PTE mitigated the severity of symptoms in CYP-induced rats by inhibiting the NLRP3 inflammasome in a dose-dependent manner. Further mechanistic investigations indicated that PTE intervention alleviated oxidative stress in CYP-induced IC in rats via activation of the Nrf2/HO-1 signaling pathway. Moreover, inhibitors of the Nrf2/HO-1 pathway effectively blocked PTE-mediated attenuation of oxidative stress. The suppression of NLRP3 inflammasome activation by PTE could also be reversed by inhibition of the Nrf2/HO-1 pathway. In vitro studies revealed that PTE enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and suppressed NLRP3 inflammasome activation in SV-HUC-1 cells exposed to lipopolysaccharide (LPS) and Adenosine Triphosphate (ATP). These findings collectively suggest that PTE treatment inhibits oxidative stress and suppresses NLRP3 inflammasome activation through modulation of the Nrf2/HO-1 pathway.

Introduction and hypothesisPatients with interstitial cystitis/bladder pain syndrome (IC/BPS) often experience chronic pelvic and even systemic pain that can be difficult to clinically manage.Pulsed electromagnetic field (PEMF) therapy, a non-invasive strategy that has shown significant efficacy for pain reduction in other chronic pain conditions, may provide benefit for pain management in patients with IC/BPS.MethodsPEMF delivery to patients occurs via a bio-electromagnetic-energy device which consists of a flexible mat (180 × 50 cm) that the patient lies on for systemic, full-body delivery and/or a flexible pad (50 × 15 cm) for targeted delivery to a specific body region (e.g., pelvic area). The duration of individual sessions, number of sessions per day, total number of sessions, and follow-up observation period vary between previously published studies. Positive outcomes are typically reported as a significant reduction in visual analog scale (VAS) pain score and functional improvement assessed using validated questionnaires specific to the condition under study.Results and conclusionsThe use of PEMF has been evaluated as a therapeutic strategy for pain management in several clinical scenarios. Randomized, double-blinded, placebo-controlled trials have reported positive efficacy and safety profiles when PEMF was used to treat non-specific low back pain, patellofemoral pain syndrome, chronic post-operative pain, osteoarthritis-related pain, rheumatoid arthritis-related pain, and fibromyalgia-related pain. Based on these positive outcomes in a variety of pain conditions, clinical trials to evaluate whether PEMF can provide a safe, non-invasive therapeutic approach to improve symptoms of chronic pain and fatigue in patients with IC/BPS are warranted.

Interstitial cystitis (IC) is a chronic bladder inflammation. Inhibition of prostaglandin G/H synthase 2 (PTGS2) is the most common method for controlling inflammation-related diseases. This study aimed to analyze the effects of hispidulin on the PTGS2 and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammation in experimental IC models. A binding activity between hispidulin and PTGS2 was measured using molecular docking. Human urothelial cells (SV-HUC-1) were stimulated by 2 ng/mL of interleukin (IL)-1β for 24 h and cultured in a medium with different concentrations of hispidulin (2.5, 5, 10, 20 µM) for 24 h to observe the expressions of PTGS2 and NLRP3 protein. Cells overexpressing PTGS2 were established by PTGS2 cDNA transfection. In the IL-1β-treated cells, the NLRP3 inflammasome was measured after 20 µM hispidulin treatment. In rats, animals were performed with three injections of 40 mg/kg cyclophosphamide (CYP) and orally treated with 50 mg/kg/day hispidulin or ibuprofen for 3 days. The bladder pain was measured using Von Frey filaments, and the bladder pathology was observed using hematoxylin and eosin (H&E) staining. The expressions of PTGS2 and NLRP3 inflammasome were also observed in the bladder tissues. A good binding activity was found between hispidulin and PTGS2 (score =  − 8.9 kcal/mol). The levels of PTGS2 and NLRP3 inflammasome were decreased with the hispidulin dose increase in the IL-1β-treated cells ( p  < 0.05). Cells overexpressing PTGS2 weakened the protective effects of hispidulin in the IL-1β-treated cells ( p  < 0.01). In the CYP-treated rats, hispidulin treatment improved the bladder pain through decreasing the nociceptive score ( p  < 0.01) and suppressed the bladder inflammation through suppressing the expressions of PTGS2 and NLRP3 inflammasome in bladder tissues ( p  < 0.01). Additionally, the results of ibuprofen treatment were similar to the effects of hispidulin in the CYP-treated rats. This study demonstrates that hispidulin may be a new alternative drug for the IC treatment that binds PTGS2 to perform its functions.

Interstitial cystitis/bladder pain syndrome (IC/BPS) plagues patients and clinicians with its unclear etiology and pathogenesis, and ineffective treatments. Destruction of epithelial tissue and proliferation of interstitial tissue are typical pathological features of IC/BPS, in which epithelial-mesenchymal transition (EMT) may play an important role. Both the increased urination frequency observed in mice with acute cystitis induced by cyclophosphamide (CYP) and the disruption of the anti-leakage barrier in urothelial cells induced by LPS are associated with the occurrence of EMT. The expression of heparanase 1 (HPSE) and syndecan-2 (SDC-2) is up-regulated in the bladder mucosa of patients with IC, and both of them can promote the development of EMT. Improvement of lower urinary tract symptoms and restoration of the uroepithelial cell anti-leakage barrier in mice with CYP-induced cystitis after treatment with the HPSE inhibitor OGT2115 and inhibited the development of EMT. We then verified that HPSE binds to SDC-2 and that SDC-2 is a key intermediate protein in the pro-EMT role of HPSE, and that EMT was inhibited by knockdown of SDC-2. SDC-2 exerts its biological function by inhibiting the ubiquitinated degradation of TGF-βR1. Here we identified a novel mechanism by which the HPSE/ SDC-2 axis promotes EMT development and thus causes epithelial dysfunction and altered voiding behavior, providing a new direction for the treatment of IC/BPS.

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic condition with severe pelvic pain and urinary symptoms significantly impairing quality of life. This study investigated the clinical relevance of the metabotropic glutamate receptor (mGluR) family in IC/BPS. Bladder biopsy samples were taken from 61 patients, including 42 Hunner-type IC, 11 non-Hunner type IC, and 8 controls without IC. Gene expression analysis revealed that mGluR2, mGluR3, and mGluR5 were significantly elevated in patients with IC/BPS compared to controls. Among these, mGluR5 showed the strongest association with pain severity, fibrosis, and lymphoplasmacytic infiltration. Patients with Hunner-type IC also exhibited increased expression of p65 and interleukin-1β, suggesting activation of inflammatory response modulation in IC/BPS. These findings suggest that mGluR5 may contribute to pain through immune response modulation in IC/BPS. Targeting mGluR5 could represent a promising therapeutic strategy to alleviate symptoms and improve patient quality of life.

Bladder pain syndrome is a chronic condition characterized by bladder pain associated with other urologic symptoms. It is a diagnosis of exclusion. Initial evaluation of suspected bladder pain syndrome includes a thorough history, physical examination, urinalysis, and urine culture, with cystoscopy reserved for further assessment. Symptom diaries help clarify the diagnosis, identify common triggers for flare-ups, and guide behavioral management strategies. Treatment begins with behavior and lifestyle modification and pelvic floor physical therapy. If this is inadequate, oral medications (eg, gabapentinoids, amitriptyline, antihistamines), intravesical instillation therapies, or procedural therapies (eg, neuromodulation) can be offered. Pain should be assessed at baseline and throughout the treatment course. Optimal treatment is multimodal, individualized, and multidisciplinary, frequently involving referral to urology or urogynecology specialists.

Interstitial cystitis (IC) is a chronic bladder disease with urinary frequency, bladder discomfort or bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC), presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC), presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001). Substantial lymphoplasmacytic inflammation (≥200 cells/mm2) was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005). Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001). These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be involved in the pathogenesis of HIC.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disease that induces mental stress, lower urinary symptoms, and pelvic pain, therefore resulting in a decline in quality of life. The present diagnoses and treatments still lead to unsatisfactory outcomes, and novel diagnostic and therapeutic modalities are needed. Although our understanding of the etiology and pathophysiology of IC/BPS is growing, the altered permeability of the impaired urothelium, the sensitized nerves on the bladder wall, and the chronic or intermittent sensory pain with inaccurate location, as well as pathologic angiogenesis, fibrosis, and Hunner lesions, all act as barriers to better diagnoses and treatments. This study aimed to summarize the comprehensive information on IC/BPS research, thereby promoting the progress of IC/BPS in the aspects of diagnosis, treatment, and prognosis. According to diverse international guidelines, the etiology of IC/BPS is associated with multiple factors, while the presence of Hunner lesions could largely distinguish the pathology, diagnosis, and treatment of non-Hunner lesions in IC/BPS patients. On the basis of the diagnosis of exclusion, the diverse present diagnostic and therapeutic procedures are undergoing a transition from a single approach to multimodal strategies targeting different potential phenotypes recommended by different guidelines. Investigations into the mechanisms involved in urinary symptoms, pain sensation, and bladder fibrosis indicate the pathophysiology of IC/BPS for further potential strategies, both in diagnosis and treatment. An overview of IC/BPS in terms of epidemiology, etiology, pathology, diagnosis, treatment, and fundamental research is provided with the latest evidence. On the basis of shared decision-making, a multimodal strategy of diagnosis and treatment targeting potential phenotypes for individual patients with IC/BPS would be of great benefit for the entire process of management. The complexity and emerging evidence on IC/BPS elicit more relevant studies and research and could optimize the management of IC/BPS patients.

Setting up the correct diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic inflammatory disease of the bladder, is a challenge, as there are neither diagnostic criteria nor reliable and non-invasive disease biomarkers available. The aim of the present study was to simultaneously determine matched serum- and urine-derived biomarkers of IC/BPS, which would provide additional insights into disease mechanisms and set the basis for further biomarker validation. Our study included 12 female patients with IC/BPS and 12 healthy controls. A total of 33 different biomarkers were measured, including cytokines and chemokines, proteins involved in extracellular matrix remodeling, adhesion molecules, growth factors, and markers of oxidative stress using enzyme linked immunoassays and multiplex technology. Heatmaps and principal component analysis based on significantly altered biomarkers, revealed urine- and serum-associated IC/BPS signatures that clearly differentiated IC/BPS patients from controls. Four biomarkers, including CCL11, BAFF, HGF and MMP9, were significantly upregulated in both serum and urine of patients with IC/BPS compared to controls. Serum levels of MMP9 were associated with disease severity and could distinguish well between IC/BPS patients with and without Hunner’s lesions. Systemic levels of MMP9 can therefore mirror the local pathology within the bladders of IC/BPS patients, and MMP9 may prove to be a useful target for the development of novel therapeutic interventions. Utilizing a comprehensive panel of both urine and serum biomarkers, identified here, holds promise for disease detection in IC/BPS patients.