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International Journal of Molecular... Nov 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disease that induces mental stress, lower urinary symptoms, and pelvic pain, therefore resulting... (Review)
Review
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.
Topics: Humans; Cystitis, Interstitial; Quality of Life; Pelvic Pain; Urinary Bladder; Chronic Pain; Fibrosis
PubMed: 36498919
DOI: 10.3390/ijms232314594 -
International Journal of Urology :... Jun 2020Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and... (Review)
Review
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 non-inflammatory 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.
Topics: Animals; Cystitis, Interstitial; Cystoscopy; Models, Animal; Pelvic Pain
PubMed: 32246572
DOI: 10.1111/iju.14229 -
Nature Reviews. Urology Mar 2019Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is... (Review)
Review
Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS.
Topics: Biomedical Research; Chronic Pain; Cystitis, Interstitial; Humans; Interdisciplinary Research; Male; Pelvic Pain; Prostatitis; Syndrome
PubMed: 30560936
DOI: 10.1038/s41585-018-0135-5 -
Signal Transduction and Targeted Therapy May 2022Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment...
Interstitial cystitis (IC) is a severely debilitating and chronic disorder with unclear etiology and pathophysiology, which makes the diagnosis difficult and treatment challenging. To investigate the role of immunity in IC bladders, we sequenced 135,091 CD45 immune cells from 15 female patients with IC and 9 controls with stress urinary incontinence using single-cell RNA sequencing (scRNA-seq). 22 immune subpopulations were identified in the constructed landscape. Among them, M2-like macrophages, inflammatory CD14 macrophages, and conventional dendritic cells had the most communications with other immune cells. Then, a significant increase of central memory CD4 T cells, regulatory T cells, GZMKCD8 T cells, activated B cells, un-switched memory B cells, and neutrophils, and a significant decrease of CD8 effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were noted in IC bladders. The enrichment analysis identified a virus-related response during the dynamic change of cell proportion, furthermore, the human polyomavirus-2 was detected with a positive rate of 95% in urine of patients with IC. By integrating the results of scRNA-seq with spatial transcriptomics, we found nearly all immune subpopulations were enriched in the urothelial region or located close to fibroblasts in IC bladders, but they were discovered around urothelium and smooth muscle cells in control bladders. These findings depict the immune landscape for IC and might provide valuable insights into the pathophysiology of IC.
Topics: CD8-Positive T-Lymphocytes; Cystitis, Interstitial; Female; Humans; Sequence Analysis, RNA; Transcriptome; Urothelium
PubMed: 35589692
DOI: 10.1038/s41392-022-00962-8 -
Advanced Science (Weinheim,... Jun 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder...
Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder microenvironment of patients with IC/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single-cell RNA sequencing (scRNA-seq) and image mass cytometry (IMC) are applied to bladder biopsies of the IC/BPS cohort. A total of 42 distinct cell clusters are identified from different groups. The increased hyperactivated Th1-biased response, but not Th2-biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non-Hunner-type IC (NHIC)/Hunner-type IC (HIC). M2/M2-like macrophage extends in the HIC and M1-like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro-inflammatory mediators, TNF-α, produced by tissue-resident macrophages and IL6, by the inflammatory fibroblasts are identified as key mediators of IC/BPS pathogenesis. Additionally, a regulatory network between different cell types is observed as a shift from structural cell communication in unaffected normal bladder to a Macrophage-Endothelial-dominated interactome in NHIC/HIC. The results demonstrate the high heterogeneity in NHIC/HIC, and provide an essential resource for diagnosis, and treatment of IC/BPS in the future by highlighting the importance of the microenvironment of bladder mucosa.
Topics: Cystitis, Interstitial; Humans; Quality of Life; Single-Cell Analysis; Urinary Bladder
PubMed: 35470584
DOI: 10.1002/advs.202106063 -
Mayo Clinic Proceedings Oct 2016Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this... (Review)
Review
Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis.
Topics: Algorithms; Anal Canal; Anus Diseases; Cystitis, Interstitial; Female; Humans; Male; Muscular Diseases; Pain; Pelvic Pain; Prostatitis
PubMed: 27712641
DOI: 10.1016/j.mayocp.2016.08.011 -
F1000Research 2018Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition associated with intense pelvic pain and bladder storage symptoms. Since diagnosis is... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition associated with intense pelvic pain and bladder storage symptoms. Since diagnosis is difficult, prevalence estimates vary with the methodology used. There is also a lack of proven imaging tools and biomarkers to assist in differentiation of IC/BPS from other urinary disorders (overactive bladder, vulvodynia, endometriosis, and prostatitis). Current uncertainty regarding the etiology and pathology of IC/BPS ultimately impacts its timely and successful treatment, as well as hampers future drug development. This review will cover recent developments in imaging methods, such as magnetic resonance imaging, that advance the understanding of IC/BPS and guide drug development.
Topics: Animals; Biomarkers; Cystitis, Interstitial; Diagnosis, Differential; Fibrosis; Humans; Magnetic Resonance Imaging
PubMed: 30473772
DOI: 10.12688/f1000research.16096.1 -
BMC Urology Jun 2019Interstitial cystitis/bladder pain syndrome (IC/BPS) and female sexual dysfunction (FSD) are common conditions that substantially reduce women's health. In particular,... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) and female sexual dysfunction (FSD) are common conditions that substantially reduce women's health. In particular, women with IC/BPS show vulvodynia, a kind of FDS that originates from consistent pain around the vulvar area. There have been many studies attempting to find the underlying mechanisms that induce the chronic pain associated with IC/BPS and vulvodynia and explain why these two conditions often coexist. Proposed theories suggest that pain hypersensitivity is being mediated by peripheral and central sensitization. However, there are still many unknown factors, such as etiologies, that can evoke pain hypersensitivity and may be linking the casual relationship between IC/BPS and vulvodynia. At present, knowledge regarding IC/BPS and vulvodynia are insufficient when considering their clinical importance. Therefore, efforts are necessary to elucidate the issues surrounding IC/BPS and vulvodynia.
Topics: Cystitis, Interstitial; Female; Humans; Vulvodynia
PubMed: 31170952
DOI: 10.1186/s12894-019-0478-0 -
Journal of Cellular and Molecular... Feb 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder pain/discomfort, urgency, urinary frequency, pelvic pain and nocturia. Although the pathophysiology of IC/BPS is not fully understood, the hypothesis suggests that mast cell activation, glycosaminoglycan (GAG) layer defects, urothelium permeability disruption, inflammation, autoimmune disorder and infection are potential mechanisms. Mesenchymal stem cells (MSCs) have been proven to protect against tissue injury in IC/BPS by migrating into bladders, differentiating into key bladder cells, inhibiting mast cell accumulation and cellular apoptosis, inhibiting inflammation and oxidative stress, alleviating collagen fibre accumulation and enhancing tissue regeneration in bladder tissues. In addition, MSCs can protect against tissue injury in IC/BPS by secreting various soluble factors, including exosomes and other soluble factors, with antiapoptotic, anti-inflammatory, angiogenic and immunomodulatory properties in a cell-to-cell independent manner. In this review, we comprehensively summarized the current potential pathophysiological mechanisms and standard treatments of IC/BPS, and we discussed the potential mechanisms and therapeutic effects of MSCs and MSC-derived exosomes in alleviating tissue injury in IC/BPS models.
Topics: Cystitis, Interstitial; Exosomes; Humans; Mesenchymal Stem Cells; Pelvic Pain; Urinary Bladder
PubMed: 34953040
DOI: 10.1111/jcmm.17132 -
Scientific Reports Feb 2021Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients... (Clinical Trial)
Clinical Trial
Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients with IC/BPS make to cope with their symptoms. This prospective study was conducted between August 2018 and June 2019. All patients had a primary symptom of suprapubic pain with a full bladder and other lower urinary tract symptoms for more than 6 weeks as well as cystoscopic findings. All participants completed our self-developed questionnaire, which included informations about their living and work environment, occupational garments, dietary habits, and personal habits. Continuous variables were compared using an independent sample t test, and categorical variables were compared using a chi-square test. We recruited 86 patients with IC/BPS and age-matched 86 controls without IC/BPS. In our study, patients with IC/BPS had more cranberry intake (45.34% vs. 5.81%, P < 0.05) than non-IC/BPS controls; the IC/BPS group had decreased consumption of coffee and spicy food; and wore less makeup or special work garments. In conclusion, patients with IC/BPS tend to make several lifestyle behavioral changes to cope with their symptoms.
Topics: Adult; Cystitis, Interstitial; Cystoscopy; Female; Humans; Lower Urinary Tract Symptoms; Middle Aged; Pain; Pain Management; Quality of Life; Surveys and Questionnaires; Urinary Bladder
PubMed: 33542405
DOI: 10.1038/s41598-021-82676-5