Mathematical Approach to Synergistic Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Series Utilizing Principal Component Analysis, Cluster Analysis, and Combination Laser Therapy.

This case series presents three patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia, demonstrating the efficacy of an individualized treatment approach using cluster analysis and combination laser therapy. Principal component analysis (PCA) was used to visualize the dynamic nature of symptom clusters and guide treatment decisions. Case 1 was a 41-year-old woman initially classified as Cluster 1 (PCA coordinates: 1.65, 0.03) transitioned to Cluster 2 (-16.93, -21.75) after bladder hydrodistension. Subsequent Fotona laser (Ljubljana, Slovenia) treatment resulted in the complete resolution of symptoms. Case 2 was a 55-year-old woman, contraindicated for hormone therapy due to breast cancer history, presented as Cluster 2 (PCA coordinates: -24.16, 8.74). Fotona laser treatment shifted her to Cluster 1 (11.22, -20.22), followed by bladder hydrodistension for complete cure. Case 3 was a 49-year-old woman, initially in Cluster 0 (PCA coordinates: 1.892, 30.11), who underwent fulguration for Hunner's lesions. Posttreatment, she moved to Cluster 2 (-24.31, 1.767) and achieved full recovery after Fotona laser therapy. The dynamic nature of symptom clusters, visualized through PCA, guided treatment decisions. The PCA transformation, represented as y =WTz, where z is the standardized symptom vector and W is the principal component matrix, allows for the objective tracking of symptom changes. Combination Fotona laser therapy, including vaginal erbium YAG and neodymium YAG, has proven effective in managing vulvar pain, particularly when hormone therapy is contraindicated. This approach, addressing both urological and gynecological aspects, resulted in sustained symptom improvement for over 12 months in all cases. This case series highlights the synergistic relationship between BPS/IC and vulvodynia, demonstrating the efficacy of comprehensive, adaptive treatment strategies guided by mathematical analysis for complex pelvic pain syndromes.

Excluding confusable diseases in patients with presumptive diagnosis of interstitial cystitis: A large patient cohort study.

OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.

The Importance of Psychological Assessment in the Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Report.

This case report emphasizes the crucial role of psychological assessment in the management of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia. A 48-year-old woman with a five-year history of refractory BPS/IC and vulvodynia presented with frequent urination, pelvic pain, and severe dyspareunia, which led to sexual aversion and divorce from her partner. Previous treatments, including lifestyle modifications, analgesics, anticholinergics, hydrodistension, intravesical dimethyl sulfoxide, and psychiatric interventions, had been ineffective. Psychological assessments using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Toronto Alexithymia Scale-20 revealed severe symptoms of depression, anxiety, and alexithymia. Due to the patient's sexual aversion and the absence of a partner, a complete Female Sexual Function Index (FSFI) could not be administered. Instead, a partial FSFI and artificial intelligence-translated reference value of the Female Sexual Distress Scale-Revised were used to assess aspects relevant to the patient's condition. The patient underwent three monthly sessions of Fotona laser therapy, erbium, and neodymium laser at one-month intervals. Treatment outcomes were evaluated using the Numeric Rating Scale-11, Vulvodynia Total, Interstitial Cystitis Symptom Index, and psychological assessment tools. At the six-month follow-up, all physical and psychological symptoms showed significant improvement and complete remission was achieved at 12 months. Despite the overall positive treatment outcomes, the patient's sexual aversion persisted, and accurate measurement was not possible, highlighting the complexity of addressing sexual function in patients with BPS/IC and vulvodynia. This case report underscores the need for a holistic approach to managing these conditions, addressing both the physical and psychological aspects of the disease.

Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

Mendelian randomization study reveals causal effects of specific gut microbiota on the risk of interstitial cystitis/bladder pain syndrome (IC/BPS).

Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research.

A systematic and comprehensive review of the role of microbiota in urinary chronic pelvic pain syndrome.

BACKGROUND: Many genitourinary tract disorders could be attributed partly to the microbiota. This study sought to conduct a systematic review of the role of the microbiota in urinary chronic pelvic pain syndrome (UCPPS). METHODS: We searched Embase, Scopus, Web of Science, and PubMed with no time, language, or study type restrictions until December 1, 2023. The JBI Appraisal Tool was used to assess the quality of the studies. Study selection followed the PRISMA statement. Studies addressing microbiome variations among patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and a control group were considered eligible. RESULTS: A total of 21 studies (1 UCPPS, 12 IC/BPS, and 8 CP/CPPS) comprising 1125 patients were enrolled in our final data synthesis. It has been shown that the reduced diversity and discrepant composition of the gut microbiota may partly be attributed to the UCPPS pathogenesis. In terms of urine microbiota, some operational taxonomic units were shown to be elevated, while others became less abundant. Furthermore, various bacteria and fungi are linked to specific clinical features. Few investigations denied UCPPS as a dysbiotic condition. CONCLUSIONS: Urinary and intestinal microbiota appear to be linked with UCPPS, comprising IC/BPS and CP/CPPS. However, given the substantial disparity of published studies, a battery of prospective trials is required to corroborate these findings.

The efficacy and safety of monoclonal antibody therapies for interstitial cystitis/bladder pain syndrome: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

Causal effects of gut microbiota on risk of interstitial cystitis: a two-sample Mendelian randomization study.

Background: The correlation between gut microbiota and interstitial cystitis has garnered significant attention in previous studies. Nevertheless, the causal relationship between them remains to be clarified. Methods: Genetic variation serves as a tool in Mendelian randomization analyses, facilitating the inference of causal relationships between exposure factors and disease outcomes. In this study, summary statistics derived from a comprehensive genome-wide association study conducted by the MiBioGen consortium were utilized as exposure factors, while interstitial cystitis data sourced from the GWAS Catalog served as the disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis. Results: IVW results confirmed that genus Haemophilus (OR = 2.20, 95% CI: 1.16-4.15, p = 0.015), genus Butyricimonas (OR = 2.26, 95% CI: 1.15-4.45, p = 0.018), genus Bacteroides (OR = 4.27, 95% CI: 1.36-13.4, p = 0.013) and Coprococcus1 (OR = 3.39, 95% CI: 1.28-8.99, p = 0.014) had a risk effect on interstitial cystitis. Sensitivity analysis did not find outlier SNPs. Conclusion: Our analysis has identified a causal relationship between specific genera and interstitial cystitis. However, further validation through randomized controlled trials is essential to substantiate these findings.

Divergent histopathological and molecular patterns in chemically induced interstitial cystitis/bladder pain syndrome rat models.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS.

Unsupervised Machine Learning Reveals a Vulvodynia-Predominant Subtype in Bladder Pain Syndrome/Interstitial Cystitis.

Background Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic condition characterized by pelvic pain and urinary symptoms. Despite its significant impact on patients' quality of life, the heterogeneity of BPS/IC symptoms and the presence of comorbidities such as vulvodynia may not be adequately captured by validated questionnaires. Identifying vulvodynia in BPS/IC patients is crucial for providing appropriate treatment options. This study aimed to identify subtypes of BPS/IC patients using unsupervised machine learning and to investigate the prevalence of vulvodynia in each subtype. Methods We conducted a prospective cross-sectional study of 123 BPS/IC patients and 64 age-matched controls. Hierarchical clustering was performed using data from validated questionnaires, including the Numerical Rating Scale-11, Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency scores, Overactive Bladder Questionnaire Short Form (OABq SF), Overactive Bladder Symptom Score (OABSS), and Pelvic Floor Distress Inventory-20. The optimal number of clusters was determined using the elbow method, and the characteristics of each cluster were analyzed. All participants underwent a vulvodynia swab test to assess vulvodynia symptoms. Results Unsupervised machine learning revealed three distinct clusters of BPS/IC patients. Clusters 0 and 2 differed significantly, with Cluster 2 characterized by significantly higher vulvodynia scores compared to other clusters (P < 0.001). In contrast, Cluster 2 had lower bladder pain scores (ICSI and ICPI) and overactive bladder symptom scores (OABq SF and OABSS) compared to other clusters. Clusters 0 and 1 were characterized by a predominance of bladder pain and urinary frequency symptoms, with Cluster 0 exhibiting more severe symptoms. Conclusions Our study identified distinct subtypes of BPS/IC patients using unsupervised machine learning, with Cluster 2 representing a vulvodynia-predominant subtype. This finding, along with the potential of targeted therapies such as non-ablative erbium YAG laser for vulvodynia, underscores the importance of assessing extravesical symptoms, particularly vulvodynia, for the diagnosis and treatment of BPS/IC. A tailored approach, including laser therapy for vulvodynia-predominant patients, may be necessary for optimal management of BPS/IC. The vulvodynia swab test plays a crucial role in assessing vulvodynia symptoms, underlining the limitations of validated questionnaires in capturing the full spectrum of BPS/IC symptoms. A comprehensive evaluation of patients, including the vulvodynia swab test, is essential for accurate subtyping and management of BPS/IC. Further research with larger sample sizes and investigation of the relationship between identified subtypes and other clinical data is warranted to advance our understanding and management of BPS/IC.

Intravesical Instillation of Hyaluronic Acid With Epidermal Growth Factor for Restoring Urothelial Denudation and Alleviating Oxidative Stress in Lipopolysaccharide-Induced Interstitial Cystitis of Rats.

PURPOSE: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. METHODS: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 µL of HA in a concentration of 0.4 mg/0.5 mL and 400 µL of NewEpi, a commercialized HA/EGF mixture containing 2 µg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. RESULTS: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1ß) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. CONCLUSION: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.

How Intravesical Platelet-Rich Plasma Can Help Patients with Interstitial Cystitis/Bladder Pain Syndrome: A Comprehensive Scoping Review.

INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. METHODS: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. RESULTS: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. CONCLUSION: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.

This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM: To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS: Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS: On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/ PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION: Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

Classification systems for chronic pelvic pain in males: a systematic review.

OBJECTIVE: To systematically review the classification systems for male chronic pelvic pain (CPP). METHODS: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), and Web of Science were searched. Any publication, with no restriction to publication date, was eligible. Publications had to propose a classification system for CPP in males or provide additional information of a system that had been identified. Systems were assessed with an adapted Critical Appraisal of Classification Systems tool. RESULTS: A total of 33 relevant publications were identified, with 22 proposing an original classification system. Systems aimed to: (i) diagnose CPP and/or differentially diagnose CPP from other conditions, (ii) differentially diagnose subtypes within CPP, or (iii) identify features that could inform underlying mechanisms and/or treatment selection. Conditions referred to as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome were most represented. Clinical signs/symptoms, pathoanatomical investigations, and presumed pain mechanisms were used for classification. Quality of systems was low to moderate, implying limitations to consider for their interpretation. CONCLUSIONS: Many classification systems for CPP in males exist. Careful consideration of their intended purpose is required. Future work should examine whether outcomes for patients are improved when decisions are guided by their use.

Characterization and Therapeutic Potential of Curcumin-Loaded Cerium Oxide Nanoparticles for Interstitial Cystitis Management.

Oxidative stress resulting from reactive oxygen species (ROS) is often considered to be the leading cause of interstitial cystitis (IC), which is a chronic inflammatory disease. Antioxidants have been proven to have promising therapeutic effects on IC. In this study, we present an antioxidant intervention for IC by introducing curcumin-loaded cerium oxide nanoparticles (Cur-CONPs). Recognizing oxidative stress as the primary contributor to IC, our research builds on previous work utilizing cerium oxide nanoparticles (CONPs) for their outstanding antioxidant and anti-inflammatory properties. However, given the need to effectively relieve acute inflammation, we engineered Cur-CONPs to harness the short-term radical-scavenging antioxidant prowess of curcumin. Through in vitro studies, we demonstrate that the Cur-CONPs exhibit not only robust antioxidant capabilities but also superior anti-inflammatory properties over CONPs alone. Furthermore, in vivo studies validate the therapeutic effects of Cur-CONPs on IC. Mice with IC subjected to the Cur-CONP treatment exhibited improved micturition behaviors, relief from pelvic pain sensitivity, and reduced expression of inflammatory proteins (IL-6, IL-1ß, TNF-α, Cox2). These findings suggest that the synergistic antioxidant properties of the Cur-CONPs that combine the sustained antioxidant properties of CONPs and acute anti-inflammatory capabilities of curcumin hold promise as a novel treatment strategy for IC.

The Efficacy of CO2 Vaginal Laser in the Treatment of Recurrent, Post-Coital and Interstitial Cystitis: A Multicentric Prospective Study.

Background: This multicentric prospective study was carried out at Fondazione Policlinico Universitario Campus Bio Medico and Ospedale di Stato of St. Marino Republic. Between 1 January 2019, and 31 December 2022, all pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis at both centers were included in the study. The main aim of the study was to assess the effectiveness of vaginal CO2 laser treatment, alone or combined with intravesical hyaluronic acid instillations, in managing cystitis symptoms, such as dysuria, pollakiuria, and urgency, across the entire patient cohort. The secondary objective was to investigate the reduction in number of annual cystitis episodes post-treatment. Methods: Each woman underwent three to four sessions of micro-ablative CO2 vaginal laser treatment. A follow-up examination was conducted 12 months after the final laser session (up to December 2023), during which a post-treatment VAS assessment evaluated dysuria, daily pollakiuria, and urgency. The enrolled patients recorded the number of cystitis episodes experienced during the 12-month pre- and post-treatment period. Results: Results indicated the laser's efficacy in reducing the total number of cystitis episodes per year and an improvement in symptoms up to one year post-treatment. Greater efficacy of the CO2 laser treatment, particularly when combined with intravesical hyaluronic acid instillation, was observed in both pre- and post- menopausal women. Conclusions: Fractional CO2 laser therapy represents a safe and efficacious, non-hormonal approach for pre- and post-menopausal women diagnosed with recurrent, post-coital, and interstitial cystitis.

A Hypothesis for Anatomical Pathways of Chronic Pelvic Pain of "Unknown Origin".

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disabling bladder condition. ESSIC, the IC/BPS society defines two types of IC/BPS: with Hunner's lesion (HL) and without. Pathogenesis is stated as unknown, with no cure possible. Scheffler in 2021 reported cystoscopically validated cure of HL IC/BPS by repair of uterosacral ligaments (USLs) and in 2022, Goeschen reported non-HL IC/BPS cure in 198 women following USL repair. Both Scheffler and Goeschen hypothesized IC/BPS may be a phenotype of the Integral Theory's Posterior Fornix Syndrome "PFS" (chronic pelvic pain, OAB, and emptying dysfunctions) and therefore potentially curable. SUMMARY: The hypothesis explores whether visceral plexuses (VPs), due to weakened USLs support, serve as a primary source of pelvic pain impulses, leading to development of an inflammatory condition - for example, IC/BPS, a chronic inflammatory condition, which shares similarities with vulvodynia and complex regional pain syndrome (CRPS). According to our hypothesis, such conditions involve axon reflexes. Stimuli such as gravity applied to unsupported nerve branches within the visceral pelvic plexus, trigger centrally propagating impulses, which then progress antidromally to influence innervated tissues through cytokine release and nociceptor stimulation, perpetuating inflammatory processes at the end organs, and pain perception. KEY MESSAGES: The hypothesis raises the question, "are IC/BPS, vulvodynia, other pain sites, even nonbacterial "chronic prostatitis" in the male, different phenotypes of the chronic pelvic pain syndrome which includes PFS. If so, the hypothesis opens several new research directions and would predict inflammatory findings in tender end organ pain sites.

Potential Urine and Serum Biomarkers in Patients with Bladder Pain Syndrome/Interstitial Cystitis.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common chronic disease, and its aetiology and pathogenesis remain unclear. This study aimed to identify potential urine and serum biomarkers in patients with IC/BPS to further understand the pathogenesis and diagnosis of the disease. METHODS: Patients with IC/BPS diagnosed and treated in the First Hospital of Hebei Medical University from 1 July 2021 to 30 July 2023 were selected. The urine and serum biomarkers of 50 patients with IC/BPS were investigated and compared with the urine and serum samples of 50 healthy controls. IBM SPSS Statistics 26.0 was used for statistical analysis of the recorded data by using chi-square test, T-test and logistic regression analysis. RESULTS: Overall, 50 patients with IC/BPS (mean age, 54.20 ± 8.15 years) were included in the study. Those with history of urinary diseases, anxiety or depression were susceptible to IC/BPS. Levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), nerve growth factor, and prostaglandin E2 (PGE2) in urine, as well as IL-8, TNF-α, and PGE2 in serum, were found to significantly increase in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). These differences were statistically significant (p < 0.05). Multifactor analysis showed that anxiety, depression, IL-6, IL-8, TNF-α and PEG2 are risk factors for patients with IC/BPS. CONCLUSIONS: Multiple biomarkers were identified in the urine and serum of patients with IC/BPS, suggesting a potential close relationship to the pathogenesis of IC/BPS.

The Effect of Montelukast on Urinary Symptoms in Children With Bladder Pain Syndrome: A Randomized Clinical Trial.

Montelukast by inhibiting leukotriene receptors in the bladder can prevent the activation of mast cells. We investigated the effectiveness of Montelukast in reducing the symptoms of children with bladder pain syndrome (BPS). In this randomized clinical trial, children were allocated into groups of intervention (Montelukast and oxybutynin) and the control (oxybutynin). At the beginning and after 14 days, questions from mothers of children about their urinary condition were asked about the frequency of nocturnal enuresis, frequent urination, urinary incontinence, urinary urgency, and their pain severity. There was no significant difference between two groups in terms of frequency of nocturnal enuresis, frequent urination, urinary incontinence, and urinary urgency. Regarding the frequency of pain distribution, the frequency of pain-free people in the Montelukast group was higher than control group (84.4% vs 56.3%, P = .023). The results showed that adding Montelukast to oxybutynin has a significant decrease in pain in children with BPS.