Pelvic Floor Muscle Dysfunction is associated with higher clinical symptoms but not bladder condition in Women with Interstitial Cystitis/Bladder Pain Syndrome

Pelvic Floor Muscle Dysfunction is associated with higher clinical symptoms but not bladder condition in Women with Interstitial Cystitis/Bladder Pain Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pelvic Floor Muscle Dysfunction is associated with higher clinical symptoms but not bladder condition in Women with Interstitial Cystitis/Bladder Pain Syndrome Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang, Hann-Chorng Kuo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4890921/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Dec, 2024 Read the published version in World Journal of Urology → Version 1 posted 13 You are reading this latest preprint version Abstract Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous multifactorial disease that is highly associated with somatic symptoms. Pelvic floor muscle pain (PFMP) is experienced by a certain percentage of women with IC/BPS. This study explored the relationship between PFMP, urinary biomarkers, and bladder condition in women with IC/BPS. Method: This study prospectively enrolled IC/BPS patients, performing vaginal digital exams and Numerical rating scales (NRS) for PFMP severity. Demographics, IC symptom index (ICSI), IC problem index (ICPI), and Beck anxiety and depression inventory were assessed. The objective assessment items included computed tomography of the bladder, urodynamic parameters, maximum bladder capacity, glomerulation grade, urine inflammatory proteins, and oxidative stress biomarkers. Result: Of 92 IC/BPS women, 85.8% PFMP exhibited significantly higher rates of dyspareunia ( p = 0.005), greater comorbidity burden ( p = 0.039), more pain-predominant phenotypes ( p = 0.004), lack of sexual activity ( p < 0.001), and elevated scores in IC symptom indices (ICSI, p = 0.003; ICPI, p < 0.001), along with increased levels of the urine biomarker MIP-1 β . However, PFMP showed no significant correlation with bladder conditions. Conclusion: PFMP was not directly associated with bladder conditions in women with IC/BPS; however, it significantly influenced the self-reported severity of IC symptoms. This finding underscores the importance of addressing PFMP in the comprehensive management of IC/BPS and highlights the necessity for synchronized multimodal treatments to effectively alleviate the overall symptom burden and perceived severity in patients with IC/BPS. Interstitial cystitis bladder pain syndrome pelvic floor muscle pelvic floor muscle pain urine biomarkers Figures Figure 1 Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and tormenting condition characterized by pelvic pain, urinary frequency, and nocturia [ 1 ]. IC/BPS, which predominantly affects women, significantly impacts the quality of life and poses substantial treatment challenges [ 2 ]. Patients are rattling unseen pain every day, longing for understanding and healing. Unfortunately, the pathogenesis of IC/BPS remains unclear [ 3 ]; the common etiology of IC/BPS is multifactorial, involving urothelial dysfunction, mast cell activation, neurogenic inflammation, and psychosocial factors [ 4 ]. Pelvic floor muscles (PFMs) support pelvic organs, control continence, and contribute to sexual function; dysfunction or pain in these muscles can lead to various urogenital symptoms [ 5 , 6 ]. A frequently overlooked aspect of IC/BPS is pelvic floor muscle pain (PFMP), which frequently coexists with bladder pain and may intensify symptom severity [ 7 ]. Patients with IC/BPS have been reported to have the overexpression of neural drives for PFMs, which could affect their symptoms and pain perception [ 8 ]. Studies have suggested that pelvic floor muscle trigger points, which are found in more than half of women with IC/BPS, may increase bladder sensitivity and discomfort [ 9 ]. Based on previous treatment guidelines, different treatment goals are required for bladder-centric and non-bladder-centric IC/BPS types [ 10 ]. Bladder and pelvic organ cross-sensitization may be caused by the activation of the spinal microglia and afferent neurons in the dorsal root ganglia [ 11 ], signaling inflammation across the gut–brain axis to organ crosstalk [ 12 ], and leading to somatic symptoms [ 13 ]. This cross-sensitization emphasizes the importance of addressing PFMP in managing bladder conditions in patients with IC/BPS to improve overall treatment outcomes. Studies have indicated that PFMP is prevalent among patients with IC/BPS, suggesting an intertwined relationship between bladder pathology and PFM dysfunction. This study explored the relationship between PFMP and bladder condition in women with IC/BPS, focusing on the correlation between self-reported symptom severity of subjective conditions, objective conditions, and urinary biomarkers with or without PFMP in patients with IC/BPS. Methods Study Design and Participants In this prospective study, 92 patients diagnosed with IC/BPS via cystoscopic hydrodistention under anesthesia at East Taiwan Medical Center were evaluated between March 2023 and March 2024, a retrospective collected and analyzed and approved by the research ethics committee of Buddhist Tzu Chi General Hospital (IRB 113-023-A). These women underwent evaluation and received treatments by urologists or gynecologists; however, their bladder or pelvic pain remained unresolved. This is a regular examination procedure; Patients were informed about the examination process and had the right to refuse participation unconditionally. Virgins were excluded from the study. IC/BPS was diagnosed according to the National Institute of Diabetes and Digestive and Kidney Diseases criteria [ 14 ]. based on chronic pelvic pain, bladder-related discomfort, and at least one urinary symptom (frequency or urgency) lasting over > 6 months [ 15 ]. Patients with refractory status were admitted for suitable treatments, such as cystoscopic hydrodistention, intravesical botulinum toxin A injection, transurethral ablation or fulguration of Hunner’s lesions, and platelet-rich plasma intravesical injection. Vaginal digital examinations, performed by a certified nurse practitioner, assessed pelvic floor muscle (PFM) condition in a comfortable and private dorsal lithotomy position before any invasive procedure Clinical data collected included delivery type, sexual condition, urinary symptoms, and comorbidities, such as depression, diabetes mellitus, heart or vessel disease, insomnia, reflux esophagitis, asthma, irritable bowel disease, constipation, lower back pain, arrhythmia, and urinary tract infections. Notably, we asked the patients which symptom they primarily experienced, such as lower urinary symptoms or nocturia. Furthermore, a pain-predominate phenotype was determined using the Numerical Rating Scale (NRS) score of ≧ 4 points, which further compares the vaginal digital examination findings. Assessment of Pelvic Floor Muscle Pain During the transvaginal digital examination, clockwise forefinger palpation of the pubovaginalis, puborectalis, iliococcygeus, coccygeus, anal sphincter, obturator internus, piriformis, and the tendinous arch was performed. Patients quantified pain using an 11-point NRS. NRS scores of 1–3 indicated mild pain, 4–6 moderate pain, and > 7 severe pain [ 16 ]. PFMP was defined as having at least one clearly defined trigger point and a pain score of ≥ 4 on the NRS; without trigger points or NRS < 4 were classified as non-PFMP. Questionnaires to Assess IC Symptom Severity and Mood Status Patients completed questionnaires on personal characteristics, sexual activity, vaginal intercourse situation, Interstitial Cystitis Symptom Index (ICSI), IC Problem Index (ICPI), NRS of self-reported bladder pain severity (BNRS), and the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) to assess the psychological situation. BAI scores of 0–18 indicate mild anxiety; 19–63 moderate to severe anxiety [ 17 ]. BDI scores of 13–19 points indicate dysphoric; 20–63 points indicate dysphoric–depressed [ 18 ]. Physiology Objective Assessments A comprehensive pre-treatment assessment was conducted, including computed tomography (CT) scans to evaluate bladder wall condition, video urodynamic study (VUDS) for voiding/storage dysfunction and uroflowmetry, and cystoscopic hydrodistention under anesthesia to determine maximum bladder capacity (MBC) and glomerulation grade. Furthermore, the first urine sample of the day was collected for inflammatory and oxidative biomarker analysis. Lower urinary tract symptoms were assessed via voiding diaries, with nocturia defined as > 2 nightly voids and urinary frequency as > 8 voids per day. The functional bladder capacity was defined as the largest voided volume recorded in a bladder diary [ 19 , 20 ]. The VUDS parameters, including the first sensation of filling (FSF), full sensation (FS), cystometric bladder capacity (CBC), detrusor pressure, maximum flow rate (Qmax), voided volume, and post-void residual urine (PVR), were examined. Urinary biomarkers, including the inflammatory proteins interleukin 8 (IL-8), IFN-gamma-inducible protein 10, monocyte chemoattractant protein-1 (MCP-1), nerve growth factor, brain-derived neurotrophic factor, eotaxin, interleukin-2, interleukin-6, macrophage inflammatory protein-1 beta (MIP-1β), RANTES, tumor necrosis factor-alpha, and prostaglandin E2 and the oxidative biomarkers 8-hydroxy-2-deoxyguanosine and 8-isoprostane, were also assessed. Statistical Analysis Statistical comparisons between groups were tested using Pearson’s chi-square test or Fisher’s exact test for categorical variables and an independent t-test or analysis of variance for continuous variables. All statistical analyses were performed using Statistical Package for the Social Sciences (version 25.0, IBM Corp., Armonk, NY, USA). P- values < 0.05 were used to denote statistical significance. Results Of the 92 IC/BPS women enrolled, the average age was 53.43 to 56.05, and 79 (85.9%) were identified to have PFMP. A higher rate of PFMP patients who underwent vaginal delivery (70.5%) was observed. Moreover, a significantly higher percentage of women with PFMP reported dyspareunia (51.9% vs. 8.3%; p = 0.005) and no sexual intercourse for > 5 years (54.4% vs. 38.4%; p < 0.001). The PFMP group also exhibited more pain-predominant phenotypes (79.5% vs. 38.5%; p = 0.004) and a higher number of comorbidities (2.33 ± 1.7 vs. 1.18 ± 1.72; p = 0.039) than the non-PFMP group. Furthermore, a higher percentage of patients in the PFMP group had nocturia than that in the non-PFMP group (85.5% vs. 58.3%; p = 0. 038). Next, patients with PFMP also had higher mean NRS score of 7.86 ± 1.97 points (PNRS) and higher ICSI (13.96 ± 4.21 vs. 10.08 ± 4.37; p = 0.003) and ICPI (13.16 ± 3.46 vs. 9.15 ± 3.95; p < 0.001) scores, reflecting greater perceived symptom severity and problem impact than non-PFMP patients. Furthermore, significantly more severe bladder pain (6.04 ± 2.67 vs. 4.31 ± 3.64; p = 0.043) was perceived by patients with PFMP even though they were not sure about the source of the pain compared with non-PFMP patients. Although BAI and BDI scores were higher in the PFMP group, the differences did not reach statistical significance (BAI: 21.45 ± 11.95 vs. 16.67 ± 7.91, p = 0.187; BDI: 23.63 ± 13.8 vs. 16.6 ± 10.7, p = 0.133), but greater psychological distress cannot be excluded among patients with PFMP ( Table 1 ) . Table 1 Demographics in different pelvic floor muscle pain condition in patients with Interstitial Cystitis/Bladder Pain Syndrome ( n = 92) Non-PFMP (n = 13) PFMP (n = 79) p value Age 53.43 ± 14.13 56.05 ± 11.02 0.448 Delivery Vaginal delivery 6 (46.2%) 55 (70.5%) 0.112 Caesarean delivery 5 (38.5%) 12 (15.6%) 0.065 Sexual activity Continue to have sex 6 (46.1%) 21 (26.5%) 0.147 No sexual intercourse within a year 1 (7.7%) 5 (6.5%) 1.000 No sexual intercourse within 3 years 1 (7.7%) 10 (12.6%) 1.000 No sexual intercourse for more than 5 years 5 (38.4%) 43 (54.4%) < 0.001* Dyspareunia 1 (8.3%) 41 (51.9%) 0.005* Duration of IC/BPS 6.83 ± 6.39 11.85 ± 10.37 0.109 Self-report pain predominates IC/BPS 5 (38.5%) 62 (79.5%) 0.004* Self-report pain site Perineum 4 (33.3%) 48 (61.5%) 0.066 Back 4 (33.3%) 22 (28.2%) 0.739 Thigh 1 (8.3%) 15 (19.2%) 0.685 Legs 1 (8.3%) 21 (26.9%) 0.280 Urethra 5 (41.7%) 35 (44.9%) 0.835 Lower urinary tract symptoms Frequency 10 (83.3%) 73 (96.1%) 0.135 Nocturia 7 (58.3%) 65 (85.5%) 0.038* Urgency 6 (50%) 57 (75%) 0.092 Dysuria 4 (33.3%) 40 (52.6%) 0.214 Urgency incontinence 1 (8.3%) 20 (26.3%) 0.279 Comorbidities 1.18 ± 1.72 2.33 ± 1.7 0.039* Type of treatment 3.42 ± 1.16 3.04 ± 1.31 0.352 PFM pain of Numerical rating scales (PNRS) 1 ± 1.15 7.86 ± 1.97 < 0.001* Beck’s anxiety inventory (BAI) 16.67 ± 7.91 21.45 ± 11.95 0.187 Beck’s depression inventory (BDI) 16.6 ± 10.7 23.63 ± 13.8 0.133 IC symptoms index (ICSI) 10.08 ± 4.37 13.96 ± 4.21 0.003* IC problem index (ICPI) 9.15 ± 3.95 13.16 ± 3.46 < 0.001* Self-report bladder pain severity (BNRS) 4.31 ± 3.64 6.04 ± 2.67 0.043* *: p < 0.05, PFMP: pelvic floor muscle pain Based on the 16 assessment sites, the mean number of painful sites was 5.15 ± 4.35, and the mean PFMP severity according to the NRS score was 6.72 ± 2.95 points in all patients with IC/BPS. According to Fig. 1, the obturator internus was the most painful site (68.5%), followed by the arcus tendineus levator ani (65.2%) and puborectalis (64.1%) (Fig. 1) . In contrast, objective bladder assessments revealed no significant differences between the PFMP and non-PFMP groups in terms of bladder CT findings and VUDS parameters, including FSF, FS, CBC, uroflowmetry parameters with detrusor pressure, Qmax, voided volume, PVR, MBC, and glomerulation grades, indicating similar performance under organ cross talk in patients with IC/BPS. However, urinary biomarkers of inflammatory proteins and oxidative stress biomarkers were explored, which revealed that the PFMP group exhibited significantly higher levels of MIP-1β (1.5 ± 1.94 vs. 0.75 ± 0.78, p = 0.026), indicating a possible inflammatory component associated with PFMP ( Table 2 ) . Table 2 Objective parameters in different pelvic floor muscle pain condition patients with Interstitial Cystitis/Bladder Pain Syndrome ( n = 92) Non-PFMP (n = 13) PFMP (n = 79) p value Computed tomography 0.249 Smooth bladder wall 6 (54.5%) 39 (60%) Focal bladder wall 5 (45.5%) 17 (26.2%) Diffuse bladder wall 0 (0%) 9 (13.8%) VUDS parameters First sensation of filling 124.31 ± 45 116.85 ± 47.3 0.597 Full sensation 214.62 ± 84.61 191.85 ± 78.52 0.341 Cytometric bladder capacity 253.92 ± 101.41 237.07 ± 115.1 0.621 Detrusor pressure 16.31 ± 7.24 19.08 ± 10.94 0.382 Maximal flow rate 11.85 ± 5.18 11.31 ± 5.78 0.754 Voided-volume 222.23 ± 100.66 212.04 ± 112.62 0.761 Post-void residual urine 45.77 ± 85.78 49.56 ± 95.64 0.894 Maximum bladder capacity 811.54 ± 141.65 793.42 ± 189.97 0.744 Glomerulation grade 1.38 ± 0.87 1.51 ± 1.12 0.710 Urine biomarkers IL-8 6.48 ± 3.71 13.9 ± 23.63 0.265 IP-10 5.35 ± 6.59 20.92 ± 64.79 0.477 MCP-1 196.55 ± 123.63 231.36 ± 201.55 0.566 NGF 0.17 ± 0.02 0.17 ± 0.02 0.772 BDNF 0.57 ± 0.18 0.59 ± 0.13 0.690 Eotaxin 5.95 ± 7.28 8.48 ± 8.37 0.330 IL-2 0.26 ± 0.04 0.23 ± 0.05 0.109 IL-6 1.83 ± 2 6.29 ± 19.75 0.529 MIP-1β 0.75 ± 0.78 1.5 ± 1.94 0.026* RANTES 6.22 ± 8.99 4.57 ± 4.77 0.411 TNF-α 1.66 ± 0.33 1.59 ± 0.4 0.539 PGE2 222.5 ± 139.38 257.42 ± 209.12 0.566 8-OHdG 61.4 ± 43.76 50.25 ± 46.72 0.428 8-isoprostane 57.64 ± 42.63 44.73 ± 34.29 0.236 PFMP: pelvic floor muscle pain, IL-8: Interleukin 8, IP-10: IFN-gamma-inducible protein 10, MCP-1: Monocyte chemoattractant protein-1, NGF: Nerve growth factor, BDNF: Brain derived neurotrophic factor, IL-2: Interleukin 2, IL-6: Interleukin 6, MIP-1β: Macrophage inflammatory protein-1 beta, TNF-α: Tumor necrosis factor alpha, PGE2: Prostaglandin E2, 8-OHdG: 8-hydroxy-2-deoxyguanosine, *: p < 0.05 Discussion The findings of this study highlighted the complexity of IC/BPS and its association with pelvic floor muscle dysfunction and revealed a higher percentage of PFMP in women with refractory IC/BPS. Although PFMP did not directly correlate with objective bladder conditions, it significantly affects the perceived severity of IC/BPS symptoms. Women with PFMP experienced higher pain levels, dyspareunia, greater comorbidity burden, and higher overall symptom burden. These findings agree with those of previous studies, which indicated that somatic factors play a critical role in IC/BPS conditions [ 21 ]. In addition, the trend toward greater psychological distress among patients with PFMP cannot be ignored. Psychological factors, including anxiety and depression, exacerbate pain perception, may contribute to the overall symptom burden in patients with IC/BPS [ 22 , 23 ], and significantly influence patients’ symptom perception and overall quality of life. Therefore, addressing psychological distress should be an integral part of the comprehensive management of IC/BPS with PFMP. Furthermore, pelvic floor dysfunction should also be considered when patients report severe lower abdominal pain because both can act as the primary signal to the spinal cord, further leading to muscle restriction and somatic syndromes [ 24 ]. The brain, bladder, or pelvic organ involves continuous crosstalk, which negatively affects the body via the bladder–gut–brain axis between the enteric and central nervous system (CNS) pathways [ 25 , 26 ]. Furthermore, 64.1% of the female patients with IC/BPS had not engaged in sexual activity or showed sexual frigidity for at least 3 years, particularly those with PFMP, with 67% experiencing dyspareunia. Studies have shown a significant association between PFM strength and sexual function [ 5 ]. This correlation underscores the interconnection between PFMP, sexual dysfunction, and bladder symptoms, suggesting that addressing one area can beneficially affect the others. Previous studies have revealed that pelvic floor dysfunction affects the rest of the body and leads to pelvic floor disorders, indicating a higher correlation between depression, anxiety severity, and the pain catastrophizing scale [ 28 ]. However, there is a lack of studies on sexual health outcomes in patients with IC/BPS [ 29 , 30 ]. Notably, this study did not identify any significant relationship between PFMP and objective bladder conditions, including CT findings, VUDS parameters, MBC, and glomerulation grades. However, the PFMP group exhibited elevated levels of the urinary inflammatory biomarker MIP-1β, suggesting the immunopathogenesis of inflammatory diseases in the CNS [ 31 , 32 ]. This finding further echoes the varied coexisting phenotypes and multiorgan dysfunctions of patients with IC/BPS [ 33 ]. This was the first study to assess pelvic floor condition using urinary biomarkers, particularly in patients with IC/BPS. Previous research has shown that higher levels of urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), IL-8, and IL-1β are associated with urinary tract infections [ 34 ]. while vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and NGAL are linked to pain severity and urinary symptoms in chronic pelvic pain syndrome (CPPS) [ 35 ]. Seminal fluid proteomics studies have identified differentially expressed proteins in patients with chronic prostatitis [ 36 ]. Interestingly, Desireddi et al . evaluated prostatic secretions and reported significantly higher MCP-1 and MIP-1α levels in patients with CPPS and a statistically significant correlation between MIP-1α and pain severity [ 37 ]. Elevated MIP-1β levels in the PFMP group in this study suggest an inflammatory component in PFMP. Cross-sensitization of afferent nerves and the communication between the bladder and the brain–gut axis may affect factors such as permeability, inflammation, infection, and dysbiosis in patients with bladder diseases [ 38 ]; women with IC/BPS displayed elevated hyperplasia sensation in pelvic dermatomes, particularly in S2–S4 [ 39 ]. A bladder–pelvis crosstalk may be observed in individuals with IC/BPS, and central sensitization may occur in both bladder-centric and non-bladder-centric patients. Vaginal examination and urinary biomarker analysis could benefit IC/BPS patients, necessitating a multifactorial assessment and multimodal therapy. This study revealed that PFMP significantly affects the severity of IC symptoms in women with IC/BPS, even though it does not directly correlate with objective bladder conditions. These findings emphasize the need to address PFMP as part of a comprehensive IC/BPS treatment plan, advocating for coordinated multimodal treatments to effectively reduce overall symptom burden and perceived severity [ 9 ]. Treatments targeting both bladder-centric and non-bladder-centric symptoms, including pelvic floor physical therapy, cognitive-behavioral therapy, and pharmacological interventions aimed at reducing inflammation and modulating pain, may be beneficial in alleviating the overall symptom burden and improving the quality of life for these patients [ 3 ]. However, limitations include subjective PFMP assessment, unclear links between PFMP and bladder conditions, and insufficient exploration of psychological factors. Future studies with larger sample sizes and objective evaluations are needed to better understand the relationship between PFMs, bladder conditions, and urinary biomarkers in IC/BPS patients. Conclusion PFMP significantly influenced the self-reported severity of IC/BPS symptoms but did not correlate with objective bladder conditions. Elevated levels of the urinary biomarker MIP-1β suggest the cross-sensitization and inflammation of PFMP in women with IC/BPS. This underscores the importance of incorporating PFMP assessment and management into the comprehensive care of patients with IC/BPS. Addressing PFMP through a multidisciplinary approach can significantly alleviate the overall symptom burden and improve patient outcomes and quality of life. Declarations Acknowledgments We thank the patients who participated in the trial and their families, and the staff at the Department of Urology, Hualien Tzu Chi Hospital who collected and validated the data. We also thank our colleagues throughout the system who referred cases. Conflict of interest All of the authors declare no competing interests, and all of them have read the final version of the manuscript and approved the submission. Ethical approval This study was performed in Hualien Tzu Chi Hospital and was approved by the ethics committee of the hospital (March/21/2024-March/20/2025/IRB 113-023-A). Informed consent Informed consent was obtained from all individual participants included in the study. All parts of this study comply with the Declaration of Helsinki. Funding This study without funding Author Contribution WR: protocol development, data analysis, data editing, manuscript writing. YH: data editing. JF: data collection, data analysis. HK: protocol development, manuscript editing, data analysis. Data availability The authors will supply the relevant data in response to reasonable requests. 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Nat reviews Urol 14(3):153–163. https://doi.org/10.1038/nrurol.2016.227 Tim S, Mazur-Bialy AI (2021) The most common functional disorders and factors affecting female pelvic floor. Life 11(12):1397. https://doi.org/10.3390/life11121397 Uzdavines A, Helmer DA, Spelman JF, Mattocks KM, Johnson AM, Chardos JF, Lynch KE, Kauth MR (2022) Sexual health assessment is vital to whole health models of care. JMIRx Med 3(3):e36266. https://doi.org/10.2196/36266 Chen A, Shahiyan RH, Anger JT (2022) Interstitial cystitis/bladder pain syndrome treatment: a systematic review of sexual health outcomes. Sex Med Reviews 10(1):71–76. https://doi.org/10.1016/j.sxmr.2020.12.005 Sobti A, Shawer S, Ballard P, Khunda A (2023) Bladder pain syndrome and sexual function: a systematic review and meta-analysis. Int Urogynecol J 34(10):2359–2371. https://doi.org/10.1007/s00192-023-05633-y Jiang Y-H, Jhang J-F, Hsu Y-H, Kuo H-C (2022) Usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome. Int J Mol Sci 23(19):12044. https://doi.org/10.3390/ijms231912044 Guo CJ, Douglas SD, Lai JP, Pleasure DE, Li Y, Williams M, Bannerman P, Song L, Ho WZ (2003) Interleukin-1β stimulates macrophage inflammatory protein‐1α and‐1β expression in human neuronal cells (NT2‐N). J Neurochem 84(5):997–1005. https://doi.org/10.1046/j.1471-4159.2003.01609.x Noor-Mohammadi E, Ligon CO, Mackenzie KD, Stratton J, Shnider SJ, Greenwood-Van Meerveld B (2023) Antinociceptive Effects of an Anti-CGRP Antibody in Rat Models of Colon-Bladder Cross-Organ Sensitization. J Pharmacol Exp Ther 387(1):4–14. https://doi.org/10.1124/jpet.122.001480 Akhlaghpour M, Haley E, Parnell L, Luke N, Mathur M, Festa RA, Percaccio M, Magallon J, Remedios-Chan M, Rosas A (2024) Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs. BMC Infect Dis 24(1):153. https://doi.org/10.1186/s12879-024-09044-2 Roy R, Stephens AJ, Daisy C, Merritt L, Newcomb CW, Yang J, Dagher A, Curatolo A, Sachdev M, McNeish B (2021) Association of longitudinal changes in symptoms and urinary biomarkers in patients with urological chronic pelvic pain syndrome: a MAPP Research Network Study. J Urol 205(2):514–523. https://doi.org/10.1097/JU.0000000000001391 Moryousef J, Blankstein U, Curtis Nickel J, Krakowsky Y, Gilron I, Jarvi K (2022) Overview of seminal fluid biomarkers for the evaluation of chronic prostatitis: a scoping review. Prostate Cancer Prostatic Dis 25(4):627–640. https://doi.org/10.1038/s41391-021-00472-8 Desireddi NV, Campbell PL, Stern JA, Sobkoviak R, Chuai S, Shahrara S, Thumbikat P, Pope RM, Landis JR, Koch AE (2008) Monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α as possible biomarkers for the chronic pelvic pain syndrome. J Urol 179(5):1857–1862. https://doi.org/10.1016/j.juro.2008.01.028 Jung J, Kim A, Yang S-H (2023) The innovative approach in functional bladder disorders: the communication between bladder and brain-gut axis. Int Neurourol J 27(1):15. https://doi.org/10.5213/inj.2346036.018 Sanses T, McCabe P, Zhong L, Taylor A, Chelimsky G, Mahajan S, Buffington T, Hijaz A, Ialacci S, Janata J (2018) Sensory mapping of pelvic dermatomes in women with interstitial cystitis/bladder pain syndrome. Neurourol Urodyn 37(1):458–465. https://doi.org/10.1002/nau.23330 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Dec, 2024 Read the published version in World Journal of Urology → Version 1 posted Editorial decision: Revision requested 24 Sep, 2024 Reviews received at journal 15 Sep, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviewers agreed at journal 05 Sep, 2024 Reviewers agreed at journal 04 Sep, 2024 Reviews received at journal 03 Sep, 2024 Reviewers agreed at journal 03 Sep, 2024 Reviews received at journal 01 Sep, 2024 Reviewers agreed at journal 19 Aug, 2024 Reviewers invited by journal 18 Aug, 2024 Editor assigned by journal 12 Aug, 2024 Submission checks completed at journal 12 Aug, 2024 First submitted to journal 10 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4890921","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":351129973,"identity":"f0d7a2d5-994b-4350-a337-d66dbfe86e20","order_by":0,"name":"Wan-Ru Yu","email":"","orcid":"","institution":"Hualien Tzu Chi Hospital, Buddhist Tzu Chi General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wan-Ru","middleName":"","lastName":"Yu","suffix":""},{"id":351129974,"identity":"947dc5ff-7059-4410-8aab-ecff54c20249","order_by":1,"name":"Jia-Fong Jhang","email":"","orcid":"","institution":"Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation","correspondingAuthor":false,"prefix":"","firstName":"Jia-Fong","middleName":"","lastName":"Jhang","suffix":""},{"id":351129975,"identity":"75764f08-adf8-4e71-a7a0-787646eb0bae","order_by":2,"name":"Yuan-Hong Jiang","email":"","orcid":"","institution":"Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation","correspondingAuthor":false,"prefix":"","firstName":"Yuan-Hong","middleName":"","lastName":"Jiang","suffix":""},{"id":351129976,"identity":"aec46af8-ad70-41af-ba29-37692879dd78","order_by":3,"name":"Hann-Chorng Kuo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAs0lEQVRIiWNgGAWjYBACAwY2xgdgBjMJWpgNDiBpkSBGC5sEWAsDsVrM2Y+lVX/4c1jenJ2B8cPHHIY6sJ34gGVP2rEbB3gOG+5sZmCWnLmNQYKgFoMb7G03DkgcTjA4DPQVL1CLGTFaCg4YkKaF7RjDgQSStJxJS5Y4cyDdcMNhxmagXyQk9xPUcvyY4YeKP9byBucPH/zwcZsNv2QDAS1IgBGklnC0jIJRMApGwSggAgAAf3s+URCDOlUAAAAASUVORK5CYII=","orcid":"","institution":"Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation","correspondingAuthor":true,"prefix":"","firstName":"Hann-Chorng","middleName":"","lastName":"Kuo","suffix":""}],"badges":[],"createdAt":"2024-08-10 09:08:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4890921/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4890921/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00345-024-05366-7","type":"published","date":"2024-12-03T15:57:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66328957,"identity":"5d112237-16ca-4505-8798-9310ecfe68d9","added_by":"auto","created_at":"2024-10-10 13:10:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":326776,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4890921/v1/ab9e32b77fc60d77add2ba44.png"},{"id":70964743,"identity":"082ca91f-31d1-4361-aaea-a2d1e9b1769e","added_by":"auto","created_at":"2024-12-09 16:15:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1065426,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4890921/v1/2739c769-7b30-4523-b5d4-56d2f77e38f2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pelvic Floor Muscle Dysfunction is associated with higher clinical symptoms but not bladder condition in Women with Interstitial Cystitis/Bladder Pain Syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and tormenting condition characterized by pelvic pain, urinary frequency, and nocturia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. IC/BPS, which predominantly affects women, significantly impacts the quality of life and poses substantial treatment challenges [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Patients are rattling unseen pain every day, longing for understanding and healing. Unfortunately, the pathogenesis of IC/BPS remains unclear [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]; the common etiology of IC/BPS is multifactorial, involving urothelial dysfunction, mast cell activation, neurogenic inflammation, and psychosocial factors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePelvic floor muscles (PFMs) support pelvic organs, control continence, and contribute to sexual function; dysfunction or pain in these muscles can lead to various urogenital symptoms [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A frequently overlooked aspect of IC/BPS is pelvic floor muscle pain (PFMP), which frequently coexists with bladder pain and may intensify symptom severity [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Patients with IC/BPS have been reported to have the overexpression of neural drives for PFMs, which could affect their symptoms and pain perception [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Studies have suggested that pelvic floor muscle trigger points, which are found in more than half of women with IC/BPS, may increase bladder sensitivity and discomfort [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on previous treatment guidelines, different treatment goals are required for bladder-centric and non-bladder-centric IC/BPS types [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Bladder and pelvic organ cross-sensitization may be caused by the activation of the spinal microglia and afferent neurons in the dorsal root ganglia [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], signaling inflammation across the gut\u0026ndash;brain axis to organ crosstalk [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and leading to somatic symptoms [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This cross-sensitization emphasizes the importance of addressing PFMP in managing bladder conditions in patients with IC/BPS to improve overall treatment outcomes.\u003c/p\u003e \u003cp\u003eStudies have indicated that PFMP is prevalent among patients with IC/BPS, suggesting an intertwined relationship between bladder pathology and PFM dysfunction. This study explored the relationship between PFMP and bladder condition in women with IC/BPS, focusing on the correlation between self-reported symptom severity of subjective conditions, objective conditions, and urinary biomarkers with or without PFMP in patients with IC/BPS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003e In this prospective study, 92 patients diagnosed with IC/BPS via cystoscopic hydrodistention under anesthesia at East Taiwan Medical Center were evaluated between March 2023 and March 2024, a retrospective collected and analyzed and approved by the research ethics committee of Buddhist Tzu Chi General Hospital (IRB 113-023-A). These women underwent evaluation and received treatments by urologists or gynecologists; however, their bladder or pelvic pain remained unresolved. This is a regular examination procedure; Patients were informed about the examination process and had the right to refuse participation unconditionally. Virgins were excluded from the study.\u003c/p\u003e \u003cp\u003eIC/BPS was diagnosed according to the National Institute of Diabetes and Digestive and Kidney Diseases criteria [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. based on chronic pelvic pain, bladder-related discomfort, and at least one urinary symptom (frequency or urgency) lasting over \u0026gt;\u0026thinsp;6 months [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Patients with refractory status were admitted for suitable treatments, such as cystoscopic hydrodistention, intravesical botulinum toxin A injection, transurethral ablation or fulguration of Hunner\u0026rsquo;s lesions, and platelet-rich plasma intravesical injection. Vaginal digital examinations, performed by a certified nurse practitioner, assessed pelvic floor muscle (PFM) condition in a comfortable and private dorsal lithotomy position before any invasive procedure\u003c/p\u003e \u003cp\u003eClinical data collected included delivery type, sexual condition, urinary symptoms, and comorbidities, such as depression, diabetes mellitus, heart or vessel disease, insomnia, reflux esophagitis, asthma, irritable bowel disease, constipation, lower back pain, arrhythmia, and urinary tract infections. Notably, we asked the patients which symptom they primarily experienced, such as lower urinary symptoms or nocturia. Furthermore, a pain-predominate phenotype was determined using the Numerical Rating Scale (NRS) score of ≧\u0026thinsp;4 points, which further compares the vaginal digital examination findings.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003eAssessment of Pelvic Floor Muscle Pain\u003c/h2\u003e \u003cp\u003eDuring the transvaginal digital examination, clockwise forefinger palpation of the pubovaginalis, puborectalis, iliococcygeus, coccygeus, anal sphincter, obturator internus, piriformis, and the tendinous arch was performed. Patients quantified pain using an 11-point NRS. NRS scores of 1\u0026ndash;3 indicated mild pain, 4\u0026ndash;6 moderate pain, and \u0026gt;\u0026thinsp;7 severe pain [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. PFMP was defined as having at least one clearly defined trigger point and a pain score of \u0026ge;\u0026thinsp;4 on the NRS; without trigger points or NRS\u0026thinsp;\u0026lt;\u0026thinsp;4 were classified as non-PFMP.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eQuestionnaires to Assess IC Symptom Severity and Mood Status\u003c/h2\u003e \u003cp\u003ePatients completed questionnaires on personal characteristics, sexual activity, vaginal intercourse situation, Interstitial Cystitis Symptom Index (ICSI), IC Problem Index (ICPI), NRS of self-reported bladder pain severity (BNRS), and the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) to assess the psychological situation. BAI scores of 0\u0026ndash;18 indicate mild anxiety; 19\u0026ndash;63 moderate to severe anxiety [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. BDI scores of 13\u0026ndash;19 points indicate dysphoric; 20\u0026ndash;63 points indicate dysphoric\u0026ndash;depressed [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePhysiology Objective Assessments\u003c/h2\u003e \u003cp\u003eA comprehensive pre-treatment assessment was conducted, including computed tomography (CT) scans to evaluate bladder wall condition, video urodynamic study (VUDS) for voiding/storage dysfunction and uroflowmetry, and cystoscopic hydrodistention under anesthesia to determine maximum bladder capacity (MBC) and glomerulation grade. Furthermore, the first urine sample of the day was collected for inflammatory and oxidative biomarker analysis. Lower urinary tract symptoms were assessed via voiding diaries, with nocturia defined as \u0026gt;\u0026thinsp;2 nightly voids and urinary frequency as \u0026gt;\u0026thinsp;8 voids per day. The functional bladder capacity was defined as the largest voided volume recorded in a bladder diary [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe VUDS parameters, including the first sensation of filling (FSF), full sensation (FS), cystometric bladder capacity (CBC), detrusor pressure, maximum flow rate (Qmax), voided volume, and post-void residual urine (PVR), were examined. Urinary biomarkers, including the inflammatory proteins interleukin 8 (IL-8), IFN-gamma-inducible protein 10, monocyte chemoattractant protein-1 (MCP-1), nerve growth factor, brain-derived neurotrophic factor, eotaxin, interleukin-2, interleukin-6, macrophage inflammatory protein-1 beta (MIP-1β), RANTES, tumor necrosis factor-alpha, and prostaglandin E2 and the oxidative biomarkers 8-hydroxy-2-deoxyguanosine and 8-isoprostane, were also assessed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical comparisons between groups were tested using Pearson\u0026rsquo;s chi-square test or Fisher\u0026rsquo;s exact test for categorical variables and an independent t-test or analysis of variance for continuous variables. All statistical analyses were performed using Statistical Package for the Social Sciences (version 25.0, IBM Corp., Armonk, NY, USA). \u003cem\u003eP-\u003c/em\u003evalues\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were used to denote statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 92 IC/BPS women enrolled, the average age was 53.43 to 56.05, and 79 (85.9%) were identified to have PFMP. A higher rate of PFMP patients who underwent vaginal delivery (70.5%) was observed. Moreover, a significantly higher percentage of women with PFMP reported dyspareunia (51.9% \u003cem\u003evs.\u003c/em\u003e 8.3%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) and no sexual intercourse for \u0026gt;\u0026thinsp;5 years (54.4% \u003cem\u003evs.\u003c/em\u003e 38.4%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The PFMP group also exhibited more pain-predominant phenotypes (79.5% \u003cem\u003evs.\u003c/em\u003e 38.5%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) and a higher number of comorbidities (2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 \u003cem\u003evs.\u003c/em\u003e 1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039) than the non-PFMP group. Furthermore, a higher percentage of patients in the PFMP group had nocturia than that in the non-PFMP group (85.5% \u003cem\u003evs.\u003c/em\u003e 58.3%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 038).\u003c/p\u003e \u003cp\u003eNext, patients with PFMP also had higher mean NRS score of 7.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97 points (PNRS) and higher ICSI (13.96\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21 \u003cem\u003evs.\u003c/em\u003e 10.08\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) and ICPI (13.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46 \u003cem\u003evs.\u003c/em\u003e 9.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.95; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) scores, reflecting greater perceived symptom severity and problem impact than non-PFMP patients. Furthermore, significantly more severe bladder pain (6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67 \u003cem\u003evs.\u003c/em\u003e 4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043) was perceived by patients with PFMP even though they were not sure about the source of the pain compared with non-PFMP patients. Although BAI and BDI scores were higher in the PFMP group, the differences did not reach statistical significance (BAI: 21.45\u0026thinsp;\u0026plusmn;\u0026thinsp;11.95 \u003cem\u003evs.\u003c/em\u003e 16.67\u0026thinsp;\u0026plusmn;\u0026thinsp;7.91, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.187; BDI: 23.63\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8 \u003cem\u003evs.\u003c/em\u003e 16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.133), but greater psychological distress cannot be excluded among patients with PFMP \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics in different pelvic floor muscle pain condition in patients with Interstitial Cystitis/Bladder Pain Syndrome (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;92)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-PFMP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePFMP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.43\u0026thinsp;\u0026plusmn;\u0026thinsp;14.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.05\u0026thinsp;\u0026plusmn;\u0026thinsp;11.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.448\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDelivery\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (70.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eSexual activity\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContinue to have sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (46.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo sexual intercourse within a year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo sexual intercourse within 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (12.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo sexual intercourse for more than 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspareunia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of IC/BPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.83\u0026thinsp;\u0026plusmn;\u0026thinsp;6.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.85\u0026thinsp;\u0026plusmn;\u0026thinsp;10.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelf-report pain predominates IC/BPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (79.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eSelf-report pain site\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (61.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (19.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLegs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (26.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrethra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.835\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eLower urinary tract symptoms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (96.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNocturia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgency incontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.039*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.352\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFM pain of Numerical rating scales (PNRS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeck\u0026rsquo;s anxiety inventory (BAI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.67\u0026thinsp;\u0026plusmn;\u0026thinsp;7.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.45\u0026thinsp;\u0026plusmn;\u0026thinsp;11.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeck\u0026rsquo;s depression inventory (BDI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.63\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIC symptoms index (ICSI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.08\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.96\u0026thinsp;\u0026plusmn;\u0026thinsp;4.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIC problem index (ICPI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelf-report bladder pain severity (BNRS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.043*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, PFMP: pelvic floor muscle pain\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on the 16 assessment sites, the mean number of painful sites was 5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;4.35, and the mean PFMP severity according to the NRS score was 6.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95 points in all patients with IC/BPS. According to Fig.\u0026nbsp;1, the obturator internus was the most painful site (68.5%), followed by the arcus tendineus levator ani (65.2%) and puborectalis (64.1%) \u003cb\u003e(Fig.\u0026nbsp;1)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eIn contrast, objective bladder assessments revealed no significant differences between the PFMP and non-PFMP groups in terms of bladder CT findings and VUDS parameters, including FSF, FS, CBC, uroflowmetry parameters with detrusor pressure, Qmax, voided volume, PVR, MBC, and glomerulation grades, indicating similar performance under organ cross talk in patients with IC/BPS. However, urinary biomarkers of inflammatory proteins and oxidative stress biomarkers were explored, which revealed that the PFMP group exhibited significantly higher levels of MIP-1β (1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94 \u003cem\u003evs.\u003c/em\u003e 0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026), indicating a possible inflammatory component associated with PFMP \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eObjective parameters in different pelvic floor muscle pain condition patients with Interstitial Cystitis/Bladder Pain Syndrome (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;92)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-PFMP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePFMP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmooth bladder wall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (54.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal bladder wall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (26.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse bladder wall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVUDS parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst sensation of filling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.31\u0026thinsp;\u0026plusmn;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116.85\u0026thinsp;\u0026plusmn;\u0026thinsp;47.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.597\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull sensation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e214.62\u0026thinsp;\u0026plusmn;\u0026thinsp;84.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e191.85\u0026thinsp;\u0026plusmn;\u0026thinsp;78.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.341\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytometric bladder capacity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253.92\u0026thinsp;\u0026plusmn;\u0026thinsp;101.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e237.07\u0026thinsp;\u0026plusmn;\u0026thinsp;115.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDetrusor pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.31\u0026thinsp;\u0026plusmn;\u0026thinsp;7.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.08\u0026thinsp;\u0026plusmn;\u0026thinsp;10.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximal flow rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.85\u0026thinsp;\u0026plusmn;\u0026thinsp;5.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.31\u0026thinsp;\u0026plusmn;\u0026thinsp;5.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.754\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVoided-volume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222.23\u0026thinsp;\u0026plusmn;\u0026thinsp;100.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e212.04\u0026thinsp;\u0026plusmn;\u0026thinsp;112.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-void residual urine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.77\u0026thinsp;\u0026plusmn;\u0026thinsp;85.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.56\u0026thinsp;\u0026plusmn;\u0026thinsp;95.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.894\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum bladder capacity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e811.54\u0026thinsp;\u0026plusmn;\u0026thinsp;141.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e793.42\u0026thinsp;\u0026plusmn;\u0026thinsp;189.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.744\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlomerulation grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.710\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine biomarkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;23.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.265\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.35\u0026thinsp;\u0026plusmn;\u0026thinsp;6.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.92\u0026thinsp;\u0026plusmn;\u0026thinsp;64.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e196.55\u0026thinsp;\u0026plusmn;\u0026thinsp;123.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e231.36\u0026thinsp;\u0026plusmn;\u0026thinsp;201.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBDNF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEotaxin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.95\u0026thinsp;\u0026plusmn;\u0026thinsp;7.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.48\u0026thinsp;\u0026plusmn;\u0026thinsp;8.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.29\u0026thinsp;\u0026plusmn;\u0026thinsp;19.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMIP-1β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.026*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRANTES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.22\u0026thinsp;\u0026plusmn;\u0026thinsp;8.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.57\u0026thinsp;\u0026plusmn;\u0026thinsp;4.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNF-α\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.539\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePGE2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222.5\u0026thinsp;\u0026plusmn;\u0026thinsp;139.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e257.42\u0026thinsp;\u0026plusmn;\u0026thinsp;209.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8-OHdG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.4\u0026thinsp;\u0026plusmn;\u0026thinsp;43.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.25\u0026thinsp;\u0026plusmn;\u0026thinsp;46.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8-isoprostane\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.64\u0026thinsp;\u0026plusmn;\u0026thinsp;42.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.73\u0026thinsp;\u0026plusmn;\u0026thinsp;34.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003ePFMP: pelvic floor muscle pain, IL-8: Interleukin 8, IP-10: IFN-gamma-inducible protein 10, MCP-1: Monocyte chemoattractant protein-1, NGF: Nerve growth factor, BDNF: Brain derived neurotrophic factor, IL-2: Interleukin 2, IL-6: Interleukin 6, MIP-1β: Macrophage inflammatory protein-1 beta, TNF-α: Tumor necrosis factor alpha, PGE2: Prostaglandin E2, 8-OHdG: 8-hydroxy-2-deoxyguanosine, *: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this study highlighted the complexity of IC/BPS and its association with pelvic floor muscle dysfunction and revealed a higher percentage of PFMP in women with refractory IC/BPS. Although PFMP did not directly correlate with objective bladder conditions, it significantly affects the perceived severity of IC/BPS symptoms. Women with PFMP experienced higher pain levels, dyspareunia, greater comorbidity burden, and higher overall symptom burden. These findings agree with those of previous studies, which indicated that somatic factors play a critical role in IC/BPS conditions [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, the trend toward greater psychological distress among patients with PFMP cannot be ignored. Psychological factors, including anxiety and depression, exacerbate pain perception, may contribute to the overall symptom burden in patients with IC/BPS [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], and significantly influence patients\u0026rsquo; symptom perception and overall quality of life. Therefore, addressing psychological distress should be an integral part of the comprehensive management of IC/BPS with PFMP. Furthermore, pelvic floor dysfunction should also be considered when patients report severe lower abdominal pain because both can act as the primary signal to the spinal cord, further leading to muscle restriction and somatic syndromes [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The brain, bladder, or pelvic organ involves continuous crosstalk, which negatively affects the body via the bladder\u0026ndash;gut\u0026ndash;brain axis between the enteric and central nervous system (CNS) pathways [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, 64.1% of the female patients with IC/BPS had not engaged in sexual activity or showed sexual frigidity for at least 3 years, particularly those with PFMP, with 67% experiencing dyspareunia. Studies have shown a significant association between PFM strength and sexual function [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This correlation underscores the interconnection between PFMP, sexual dysfunction, and bladder symptoms, suggesting that addressing one area can beneficially affect the others. Previous studies have revealed that pelvic floor dysfunction affects the rest of the body and leads to pelvic floor disorders, indicating a higher correlation between depression, anxiety severity, and the pain catastrophizing scale [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, there is a lack of studies on sexual health outcomes in patients with IC/BPS [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, this study did not identify any significant relationship between PFMP and objective bladder conditions, including CT findings, VUDS parameters, MBC, and glomerulation grades. However, the PFMP group exhibited elevated levels of the urinary inflammatory biomarker MIP-1β, suggesting the immunopathogenesis of inflammatory diseases in the CNS [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This finding further echoes the varied coexisting phenotypes and multiorgan dysfunctions of patients with IC/BPS [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis was the first study to assess pelvic floor condition using urinary biomarkers, particularly in patients with IC/BPS. Previous research has shown that higher levels of urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), IL-8, and IL-1β are associated with urinary tract infections [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. while vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and NGAL are linked to pain severity and urinary symptoms in chronic pelvic pain syndrome (CPPS) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Seminal fluid proteomics studies have identified differentially expressed proteins in patients with chronic prostatitis [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Interestingly, Desireddi \u003cem\u003eet al\u003c/em\u003e. evaluated prostatic secretions and reported significantly higher MCP-1 and MIP-1α levels in patients with CPPS and a statistically significant correlation between MIP-1α and pain severity [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Elevated MIP-1β levels in the PFMP group in this study suggest an inflammatory component in PFMP. Cross-sensitization of afferent nerves and the communication between the bladder and the brain\u0026ndash;gut axis may affect factors such as permeability, inflammation, infection, and dysbiosis in patients with bladder diseases [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]; women with IC/BPS displayed elevated hyperplasia sensation in pelvic dermatomes, particularly in S2\u0026ndash;S4 [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. A bladder\u0026ndash;pelvis crosstalk may be observed in individuals with IC/BPS, and central sensitization may occur in both bladder-centric and non-bladder-centric patients. Vaginal examination and urinary biomarker analysis could benefit IC/BPS patients, necessitating a multifactorial assessment and multimodal therapy.\u003c/p\u003e \u003cp\u003eThis study revealed that PFMP significantly affects the severity of IC symptoms in women with IC/BPS, even though it does not directly correlate with objective bladder conditions. These findings emphasize the need to address PFMP as part of a comprehensive IC/BPS treatment plan, advocating for coordinated multimodal treatments to effectively reduce overall symptom burden and perceived severity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Treatments targeting both bladder-centric and non-bladder-centric symptoms, including pelvic floor physical therapy, cognitive-behavioral therapy, and pharmacological interventions aimed at reducing inflammation and modulating pain, may be beneficial in alleviating the overall symptom burden and improving the quality of life for these patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, limitations include subjective PFMP assessment, unclear links between PFMP and bladder conditions, and insufficient exploration of psychological factors. Future studies with larger sample sizes and objective evaluations are needed to better understand the relationship between PFMs, bladder conditions, and urinary biomarkers in IC/BPS patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePFMP significantly influenced the self-reported severity of IC/BPS symptoms but did not correlate with objective bladder conditions. Elevated levels of the urinary biomarker MIP-1β suggest the cross-sensitization and inflammation of PFMP in women with IC/BPS. This underscores the importance of incorporating PFMP assessment and management into the comprehensive care of patients with IC/BPS. Addressing PFMP through a multidisciplinary approach can significantly alleviate the overall symptom burden and improve patient outcomes and quality of life.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patients who participated in the trial and their families, and the staff at the Department of Urology, Hualien Tzu Chi Hospital who collected and validated the data. We also thank our colleagues throughout the system who referred cases.\u003c/p\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003e All of the authors declare no competing interests, and all of them have read the final version of the manuscript and approved the submission.\u003c/p\u003e \u003ch2\u003eEthical approval\u003c/strong\u003e \u003cp\u003e This study was performed in Hualien Tzu Chi Hospital and was approved by the ethics committee of the hospital (March/21/2024-March/20/2025/IRB 113-023-A).\u003c/p\u003e\u003ch2\u003eInformed consent\u003c/strong\u003e \u003cp\u003e Informed consent was obtained from all individual participants included in the study. All parts of this study comply with the Declaration of Helsinki.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study without funding\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eWR: protocol development, data analysis, data editing, manuscript writing. 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Neurourol Urodyn 37(1):458\u0026ndash;465. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/nau.23330\u003c/span\u003e\u003cspan address=\"10.1002/nau.23330\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Interstitial cystitis, bladder pain syndrome, pelvic floor muscle, pelvic floor muscle pain, urine biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-4890921/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4890921/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eInterstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous multifactorial disease that is highly associated with somatic symptoms. Pelvic floor muscle pain (PFMP) is experienced by a certain percentage of women with IC/BPS. This study explored the relationship between PFMP, urinary biomarkers, and bladder condition in women with IC/BPS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eThis study prospectively enrolled IC/BPS patients, performing vaginal digital exams and Numerical rating scales (NRS) for PFMP severity. Demographics, IC symptom index (ICSI), IC problem index (ICPI), and Beck anxiety and depression inventory were assessed. The objective assessment items included computed tomography of the bladder, urodynamic parameters, maximum bladder capacity, glomerulation grade, urine inflammatory proteins, and oxidative stress biomarkers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult: \u003c/strong\u003eOf 92 IC/BPS women, 85.8% PFMP exhibited significantly higher rates of dyspareunia (\u003cem\u003ep\u003c/em\u003e = 0.005), greater comorbidity burden (\u003cem\u003ep\u003c/em\u003e = 0.039), more pain-predominant phenotypes (\u003cem\u003ep\u003c/em\u003e = 0.004), lack of sexual activity (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and elevated scores in IC symptom indices (ICSI, \u003cem\u003ep\u003c/em\u003e = 0.003; ICPI, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), along with increased levels of the urine biomarker MIP-1\u003cem\u003eβ\u003c/em\u003e. However, PFMP showed no significant correlation with bladder conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003ePFMP was not directly associated with bladder conditions in women with IC/BPS; however, it significantly influenced the self-reported severity of IC symptoms. This finding underscores the importance of addressing PFMP in the comprehensive management of IC/BPS and highlights the necessity for synchronized multimodal treatments to effectively alleviate the overall symptom burden and perceived severity in patients with IC/BPS.\u003c/p\u003e","manuscriptTitle":"Pelvic Floor Muscle Dysfunction is associated with higher clinical symptoms but not bladder condition in Women with Interstitial Cystitis/Bladder Pain Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-10 13:10:03","doi":"10.21203/rs.3.rs-4890921/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-24T20:03:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-15T21:25:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195850599794015891527752783129718172631","date":"2024-09-09T08:55:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157335680650529688256285135351429903101","date":"2024-09-05T19:44:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"312974059709833880991746490327059840999","date":"2024-09-04T08:08:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-03T17:48:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227358513593302766102635386007414882813","date":"2024-09-03T16:55:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-01T15:34:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286333169610943824496178466207955935321","date":"2024-08-19T18:07:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-18T10:31:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-12T18:23:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-12T18:04:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"World Journal of Urology","date":"2024-08-10T09:07:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"world-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"wjur","sideBox":"Learn more about [World Journal of Urology](https://link.springer.com/journal/345)","snPcode":"345","submissionUrl":"https://submission.nature.com/new-submission/345/3","title":"World Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"85f2626c-d1af-430b-bca5-826c0bbc52c6","owner":[],"postedDate":"October 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-09T16:03:37+00:00","versionOfRecord":{"articleIdentity":"rs-4890921","link":"https://doi.org/10.1007/s00345-024-05366-7","journal":{"identity":"world-journal-of-urology","isVorOnly":false,"title":"World Journal of Urology"},"publishedOn":"2024-12-03 15:57:44","publishedOnDateReadable":"December 3rd, 2024"},"versionCreatedAt":"2024-10-10 13:10:03","video":"","vorDoi":"10.1007/s00345-024-05366-7","vorDoiUrl":"https://doi.org/10.1007/s00345-024-05366-7","workflowStages":[]},"version":"v1","identity":"rs-4890921","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4890921","identity":"rs-4890921","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}