OBJECTIVES: To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice. METHODS: Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells. RESULTS: PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA. CONCLUSIONS PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.
Animals ; Cystitis, Interstitial/drug therapy* ; Gastrointestinal Microbiome/drug effects* ; Pentosan Sulfuric Polyester/therapeutic use* ; Cyclophosphamide/adverse effects* ; Mice, Inbred C57BL ; Female ; Mice ; Bile Acids and Salts/metabolism* ; Urinary Bladder ; Fecal Microbiota Transplantation ; Humans

OBJECTIVE: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). METHODS: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. RESULTS: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). CONCLUSION Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.
Humans ; Female ; Cystitis, Interstitial/drug therapy* ; Administration, Intravesical ; Retrospective Studies ; Sodium Bicarbonate/therapeutic use* ; Treatment Outcome ; Lidocaine/therapeutic use* ; Heparin/therapeutic use* ; Electrocoagulation

OBJECTIVE: To establish a model of bladder pain syndrome in SD rats by cyclophosphamide intraperitoneal injection, to evaluate the effectiveness of the model from the urodynamic and histological levels, to lay a zoological foundation for the clinical study of bladder pain syndrome, and to further guide clinical treatment. METHODS: Thirty-two 8-week-old SD rats were randomly divided into 4 groups, including acute test group, acute control group, chronic test group, and chronic control group, with 8 rats in each group. The acute test group received intraperitoneal injection of cyclophosphamide 150 mg/kg immediately after the measurement of urodynamic data on the first day, and urodynamic examination was performed again 2 days later. After that, the rats were sacrificed to obtain bladder tissue. In the chronic test group, after measuring the baseline data of urodynamics on the first day, cyclophosphamide 75 mg/kg was intraperitoneally injected on the first, fourth, and seventh days, and the rats were sacrificed after measuring the urodynamic data again on the eighth day to obtain bladder tissue. The acute control group and the chronic control group were injected with the same amount of normal saline during intraperitoneal injection, and the urodynamic testing time point were consistent with the corresponding test groups. Histopathological changes of the bladder were assessed by HE staining. RESULTS: In each acute and chronic group, there were no intragroup differences in baseline urodynamic levels between the test and control groups. The urodynamic maximum bladder volume was significantly reduced in the acute test group after administration(t=-2.961, P < 0.05), histologically, severe interstitial edema, obvious inflammatory cell infiltration, mucosal edema and submucosal hemorrhage, and partial urothelium were absent could be seen, which were consistent with acute cystitis performance. The urodynamic maximum bladder capacity was significantly reduced in the chronic test group after administration (t=-3.886, P < 0.05), and the bladder compliance was lower than that in the control group, but not significant, the histological manifestations were urothelial exfoliation, interstitial edema, submucosal hemorrhage, infiltration of inflammatory cells such as lymphocytes, and dense vascular distribution. CONCLUSION In the acute test group, a single intraperitoneal injection of cyclophosphamide could induce acute bladder inflammation in the rats. In the chronic test group, repeated injections of cyclophosphamide could induce histological changes in chronic inflammation of chronic bladder pain syndrome in the rats. But the bladder function was not significantly impaired.
Animals ; Cyclophosphamide/therapeutic use* ; Cystitis/pathology* ; Cystitis, Interstitial/drug therapy* ; Disease Models, Animal ; Hemorrhage ; Rats ; Rats, Sprague-Dawley ; Urodynamics

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL 32) and "Huiyang" (BL 35) on the pain, urodynamic and the expressions of transient receptor poteintial vanilloid 1 (TRPV1) and P2X3 receptors in bladder of rats with interstitial bladder (IC), and to explore the possible mechanism on EA for IC. METHODS: A total of 24 Wistar female rats were randomly divided into a blank group, a model group and an EA group, 8 rats in each group. In the model group and the EA group, IC model was established by intraperitoneal injection of cyclophosphamide by 150 mg/kg at once. EA was applied at "Ciliao" (BL 32) and "Huiyang" (BL 35) in the EA group for 20 min, with continuous wave, 30 Hz in frequency, once a day for 3 consecutive days. Mechanical pain threshold of bladder and urodynamic indexes (first urination time, bladder effective volume and urination pressure) were observed after model establishment and after intervention, the expressions of TRPV1 and P2X3 receptors in the bladder were detected by Western blot. RESULTS: After model establishment, the mechanical pain threshold of bladder was decreased in the model group and the EA group compared with that in the blank group (P<0.01). After intervention, the mechanical pain threshold of bladder in the model group was lower than the blank group (P<0.01), and that in the EA group was higher than the model group (P<0.01). The urodynamic of the rats in the blank group was normal, obvious abnormal contraction during the filling period of bladder was found in the rats of the model group, while no abnormal contraction during the filling period was found in the rats of the EA group. After model establishment, in the model group and the EA group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.01). After intervention, in the model group, the first urination time was earlier than the blank group (P<0.01), while bladder effective volume and urination pressure were lower than the blank group (P<0.05); in the EA group, the first urination time was later than the model group (P<0.05), while bladder effective volume and urination pressure were higher than the model group (P<0.05). Compared with the blank group, the protein expressions of TRPV1 and P2X3 receptors in bladder were up-regulated in the model group (P<0.01); compared with the model group, the protein expressions of TRPV1 and P2X3 receptors in bladder were down-regulated in the EA group (P<0.05). CONCLUSION EA can relieve bladder pain and improve urodynamic in IC rats. The mechanism may be related to the down-regulation on the expressions of TRPV1 and P2X3 receptors and the further inhibition on the abnormal input of bladder signal.
Rats ; Female ; Animals ; Cystitis, Interstitial/therapy* ; Electroacupuncture ; Urinary Bladder ; Receptors, Purinergic P2X3/metabolism* ; Rats, Sprague-Dawley ; Rats, Wistar ; Pain ; Antineoplastic Agents ; TRPV Cation Channels/metabolism*

OBJECTIVE: To evaluate the quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS), to compare the difference between IC/BPS and overactive bladder (OAB) pain syndrome, and to explore the related factors affecting the quality of life of IC/BPS patients. METHODS: The demographic data of female outpatients with IC/BPS in Beijing Hospital and other medical centers in China were collected. The quality of life of the patients was investigated by multi-angle questionnaires and compared with the data of OAB patients. According to the influence degree of quality of life, the patients with IC/BPS were divided into mild-moderate group and severe group. RESULTS: In this study, 109 patients with IC/BPS were included. The average age was (46.4±14.3) years and the average course of disease was (39.4±51.6) months. Compared with the OAB patients, the patients in IC/BPS group had a longer average course of disease (P=0.008), a lower proportion of the patients of first visit for the disease (P < 0.001), a higher score of the American Urological Association symptom index (AUA-SI) (P < 0.001), a lower body mass index (BMI) ratio (P=0.016), and a lower incidence of constipation (P=0.006). IC/BPS had the greatest impact on family life, followed by social activity. The score of IC/BPS related symptoms on family life was significantly higher than that of the OAB group (P=0.003). The top three symptoms of the IC/BPS patients were pain (45%), frequency (28%) and urgency (17%). The score of quality of life in the IC/BPS patients was significantly higher than that in the OAB patients (P < 0.001). Caffeine intake (P=0.034) and constipation (P=0.003) might be the factors influencing the quality of life of the patients with IC/BPS. CONCLUSION IC/BPS has a great influence on the quality of life of patients. Caffeine intake and constipation may be related factors affecting the quality of life of patients with IC/BPS. Urologists should recommend changes in diet and lifestyle to reduce symptoms and improve the patients' quality of life.
Adult ; Cystitis, Interstitial/epidemiology* ; Female ; Humans ; Middle Aged ; Pain ; Quality of Life ; Surveys and Questionnaires ; Urinary Bladder, Overactive/epidemiology*

PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.
Cystitis, Interstitial ; Dimethyl Sulfoxide ; Humans ; Methods ; Pilot Projects ; Recurrence

PURPOSE: To identify risk factors for interstitial cystitis (IC), a chronic bladder disorder that may have a significant detrimental impact on quality of life, in the general population and in individuals with depression. METHODS: This was a comparative study using a US claims database. Adults who had records of a visit to the health system in 2010 or later were included. The outcome was the development of IC within 2 years after the index date. The index date for the general population was the first outpatient visit, and for individuals with depression, it was the date of the diagnosis of depression. IC was defined using the concepts of ulcerative and IC. We included all medical conditions present any time prior to the index visit as potential risk factors. RESULTS: The incidence of IC was higher in individuals with depression than in the general population. Of the 3,973,000 subjects from the general population, 2,293 (0.06%) developed IC within 2 years. Of the 249,200 individuals with depression, 320 (0.13%) developed IC. The characteristics of the individuals who developed IC were similar in both populations. Those who developed IC were slightly older, more likely to be women, and had more chronic pain conditions, malaise, and inflammatory disorders than patients without IC. In the general population, subjects who developed IC were more likely to have mood disorders, anxiety, and hypothyroidism. CONCLUSIONS: The incidence of IC was higher in individuals with depression. Subjects who developed IC had more chronic pain conditions, depression, malaise, and inflammatory disorders.
Adult ; Anxiety ; Chronic Pain ; Cystitis, Interstitial ; Depression ; Diagnosis ; Female ; Humans ; Hypothyroidism ; Incidence ; Inflammation ; Mood Disorders ; Outpatients ; Quality of Life ; Risk Factors ; Ulcer ; Urinary Bladder

OBJECTIVE: To explore the clinical efficacy of electroacupuncture nerve stimulation therapy (ENST) for interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: A total of 68 patients with IC/PBS were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the observation group were treated with ENST; abdominal four acupoints and sacral four acupoints were connected with a pair of electrodes and treated alternately every other day. The ENST was given 50 min per times, three times a week for 3 months. The patients in the control group were treated with perfusion therapy of four-medication combination (heparin sodinm, lidocaine, sodium bicarbonate, gentamicin sulfate), twice a week for the first 6-8 weeks, followed by twice per month for 3 months. The infusion fluid remained for 1 h before discharging. The O' Leary-Sant score, including interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI), 24 h urination frequency, visual analogue scale (VAS) and maximum bladder volume were observed before treatment and treatment of 1 month, 3 months and 6 months after treatment respectively; the adverse events during the treatment were also recorded. RESULTS: Compared before treatment, the O'Leary-Sant score (ICSI, ICPI), 24 h urination frequency, VAS and maximum bladder volume in the two groups were improved after 1, 3 months treatment and 6 months after treatment (all <0.05). The scores of ICSI, ICPI, VAS and 24 h urination frequency in the observation group were significantly lower than those in the control group (<0.05). The maximum bladder volume in the observation group was significantly higher than that in the control group (<0.05). Six months after treatment, the total effective rate in the observation group was 87.5% (28/32), which was higher than 69.7% (23/33) in the control group (<0.01). No significant adverse events occurred during the treatment. CONCLUSION ENST could effectively relieve the clinical symptoms of IC/PBS, but its long-term efficacy needs further observation.
Cystitis, Interstitial ; therapy ; Electroacupuncture ; Humans ; Pain ; Pain Management ; Treatment Outcome ; Urinary Bladder Diseases ; therapy

PURPOSE: To evaluate whether mild chemical irritation of the bladder in neonatal rats is associated with persistent vanilloid receptor transient receptor potential vanilloid subfamily 1 (TRPV1) activity in adult rats. METHODS: Female Sprague-Dawley rats were used. Ten-day-old rat pups underwent bladder sensitization via intravesical infusion of 0.2% acetic acid in saline with or without prior bladder desensitization with capsaicin. After 8 weeks, 3 groups of rats (control [group 1], bladder sensitization [group 2], and bladder desensitization [group 3]) underwent cystometry. Inflammation of bladder tissue and the expression of TRPV1 in bladder tissue and dorsal root ganglia (DRG) were also evaluated. RESULTS: The bladder sensitization group showed more frequent voiding contractions. TRPV1 expression in adult bladder tissue was elevated in group 2. TRPV1 mRNA levels in the bladder and DRG were significantly higher in group 2 than in group 1. Moreover, group 2 had significantly more DRG neurons (identified by uptake of the retrograde label Fast Blue) that exhibited TRPV1 immunoreactivity. CONCLUSIONS: We found a significant association between neonatal bladder sensitization and persistent TRPV1 activity in adult rats. This is the first study to focus on the underlying pathogenesis of bladder overactivity from childhood to adulthood. Our findings could lead to the development of new strategies for the treatment and prevention of adult urinary symptoms arising from childhood urinary tract dysfunction.
Acetic Acid ; Adult* ; Animals ; Capsaicin ; Cystitis, Interstitial ; Diagnosis-Related Groups ; Female ; Ganglia, Spinal ; Humans ; Inflammation ; Neurons ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; TRPV Cation Channels ; Urinary Bladder* ; Urinary Tract ; Urinary Tract Infections

PURPOSE: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). METHODS: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response (0.01–10μM) was determined for each strip with the mucosa intact or denuded. RESULTS: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by 1μM atropine in both control and FIC bladder strips. CONCLUSIONS: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.
Acetylcholine ; Animals ; Atropine ; Baths ; Cats ; Cystitis ; Cystitis, Interstitial* ; Mucous Membrane ; Serotonin* ; Transducers ; Urinary Bladder ; Urothelium