Latest advances in the diagnosis and treatment of interstitial cystitis/bladder pain syndrome / 现代泌尿外科杂志

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by pain, oppressing sensation, or discomfort associated with the bladder, accompanied by lower urinary tract symptoms, lasting for more than 6 weeks (or 6 months). Since IC/BPS was first reported, its diagnosis and treatment have been a challenge to clinicians. This article will review its classification and phenotype, fundamental research, imaging, symptom score, cystoscopy, treatment and potential therapeutic targets.

Aspectos psicológicos asociados a la cistitis intersticial / Psychological aspects associated with interstitial cystitis

La cistitis intersticial o síndrome de vejiga dolorosa es un padecimiento complejo asociado a dolor pélvico intenso con síntomas urinarios como urgencia, polaquiuria, dispareunia, incontinencia y nicturia, que afecta de manera importante la calidad de vida y las relaciones sociales y productivas del paciente. La evidencia muestra que el abordaje de los factores psicosociales que afectan a los pacientes con esta enfermedad es esencial. El tratamiento debe ir más allá de los síntomas clínicos y considerar los aspectos individuales de cada paciente, su salud mental, sus experiencias de vida y su comorbilidad, dado que los trastornos psicológicos como la ansiedad, la depresión y el estrés postraumático pueden influir en la manera en que se percibe el dolor, y están ligados con la gravedad y el empeoramiento de los síntomas. La literatura presenta a la intervención psicológica desde el enfoque cognitivo conductual como un medio para disminuir el dolor, la ansiedad y el catastrofismo, dando al paciente herramientas que le permitan obtener una sensación de control a partir del afrontamiento y mejorar su calidad de vida.

Interstitial cystitis or painful bladder syndrome is a complex condition associated with intense pelvic pain with urinary symptoms such as urgency, pollakiuria, dyspareunia, incontinence and nocturia that significantly affects the patient's quality of life, social and productive relationships. Evidence shows that addressing the psychosocial factors that affect patients with this disease is essential. Treatment should go beyond clinical symptoms and consider the individual aspects of each patient, their mental health, life experiences and comorbidities, since psychological disorders such as anxiety, depression and post-traumatic stress disorder can influence the way pain is perceived and are linked to the severity and worsening of symptoms. The literature presents psychological intervention from the cognitive-behavioral approach to reduce pain, anxiety and catastrophism, giving the patient tools that allow him to obtain a sense of control from coping tools that allow him to improve his quality of life.

Intravascular ketamine infusion for the treatment of chronic pain and depression. Case report / Infusão intravascular de cetamina para o tratamento de dor crônica e depressão. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic pain and depression are two comorbidities that correlate at the molecular level in the central nervous system and cause sufering to the patient, being dificult to be managed. In recent years, several studies have shown significant analgesic and antidepressant efects from intravascular infusion of ketamine, being a promising alternative option for refractory patients. Tus, the aim of the study was to report the case of a patient with refractory chronic pain and depression submitted to serial ketamine single dose infusions. CASE REPORT: Female patient, 33 years old, diagnosed with interstitial cystitis 13 years ago with refractory chronic pain and depression, submitted to serial infusions of intravascular ketamine. Tree serial infusions were performed, providing a significant improvement in pain and mood. However, the patient could not tolerate the adverse efects, particularly, the transient sensation of impending death and panic attack, and abandoned the treatment. CONCLUSION: Ketamine is a safe and promising treatment option for chronic pain and depression and can promote significant, albeit transient, pain and mood relief using subanesthetic dosage. However, its adverse efects can be an important limitation for therapeutic success. Standardized clinical studies are needed to better understand the relationship between chronic pain and depression and to establish the best therapeutic approach.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor crônica e a depressão são duas comorbidades que se correlacionam em nível molecular no sistema nervoso central e promovem sofrimento ao paciente, sendo de difícil manejo. Nos últimos anos, diversos estudos demonstraram efeitos analgésicos e antidepressivos significativos a partir da infusão intravascular de cetamina, sendo uma opção alternativa para pacientes refratários ao tratamento convencional. Assim, o objetivo do estudo foi relatar o caso de uma paciente com dor crônica e depressão refratária submetida a infusões seriadas de doses únicas de cetamina. RELATO DO CASO: Paciente do sexo feminino, 33 anos, diagnosticada com cistite intersticial há 13 anos com refratariedade no manejo da dor e da depressão, submetida a infusões seriadas de cetamina intravascular. Foram realizadas 3 infusões seriadas que proporcionaram uma melhora significativa na dor e no humor. Entretanto, a paciente não tolerou os efeitos adversos, particularmente, de sensação de morte iminente e ataque de pânico, e abandonou o tratamento. CONCLUSÃO: A cetamina é uma opção de tratamento promissora para dor crônica e depressão e pode promover alívio significativo, embora transitório, da dor e humor utilizando dose subanestésica. No entanto, seus efeitos adversos podem ser uma limitação para o sucesso terapêutico. Estudos clínicos padronizados são necessários para compreender melhor a relação entre dor crônica e depressão e para estabelecer a melhor abordagem terapêutica.

Quality of life and related factors in patients with interstitial cystitis/bladder pain syndrome / 北京大学学报(医学版)

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.

Temperature selection of intravesical sodium hyaluronate in the treatment of interstitial cystitis / 中国临床药理学与治疗学

AIM: To investigate the efficacy of bladder infusion of sodium hyaluronate (HA) in the treatment of interstitial cystitis (IC) at different temperatures. METHODS: Forty patients with IC admitted in our hospital from March 2018 to April 2019 were simply randomized and divided into two groups for prospective study, with 20 patients in each group. The temperature of perfusion fluid in normal temperature group was 37 ℃, and the temperature of perfusion fluid in high temperature group was 43 ℃. Compared the two groups before treatment, one month after treatment, and three months after treatment of interstitial cystitis problem score (ICPI), interstitial bladder symptoms score (ICSI), pre-veeing pain visual analogue score (VAS), and anxiety self-assessment scale (SAS), depression self-assessment scale (SDS), quality of life score (QOL), daily urination times, maximum bladder volume, bladder mast cell count, and immune factors [interleukin (IL)-6, IL-10] expression. RESULTS:The ICPI, ICSI, VAS, SAS, and SDS scores of the hyperthermia group were lower than those of the normal temperature group after one month and three months of treatment, and the QOL scores were higher than those of the normal temperature group after three months of treatment (P0.05). CONCLUSION:Compared with 37 ℃, intravesical instillation of HA in the treatment of IC can effectively relieve the clinical symptoms and signs of patients when the perfusion fluid is at a temperature of 43 ℃, and it improves the maximum bladder capacity and anxiety and depression, improves the quality of life of patients, which is safe and reliable. The mechanism may be related to the regulation of large cell, IL-6, IL-10 of bladder mucosa.

Efficacy of Frankincense and Myrrha in Treatment of Acute Interstitial Cystitis/Painful Bladder Syndrome / 中国结合医学杂志

OBJECTIVE@#To investigate the efficacy of frankincense and myrrha in the treatment of acute interstitial cystitis/painful bladder syndrome (IC/PBS).@*METHODS@#The effects of frankincense and myrrha on the proliferation and migration of primary human urothelial cells (HUCs) were assessed in vitro. In the animal study, 48 virgin female rats were randomized into 4 groups (12 in each group): (1) control group (saline-injected control); (2) cyclophosphamide (CYP) group (intraperitoneal injected 150 mg/kg CYP); (3) CYP + pentosan polysulfate sodium group (orally received 50 mg/kg pentosan polysulfate sodium); and (4) CYP + frankincense and myrrha group [orally received frankincense (200 mg/kg) and myrrha (200 mg/kg)]. Rats orally received pentosan polysulfate sodium or frankincense and myrrha on day 1, 2, and 3. The experiments were performed on day 4. Pain and cystometry assessment behavior test were performed. Voiding interval values were assessed in rats under anesthesia. Finally, immunohistochemistry and Western blot were used to confirm the location and level, respectively, of cell junction-associated protein zonula occludens-2 (ZO-2) expression.@*RESULTS@#Low dose frankincense and myrrha increased cell proliferation and migration in HUCs compared with control (P<0.05). Rats with acute IC/PBS rats exhibited lower voiding interval values, pain tolerance, and ZO-2 expression (P<0.05). Voiding interval values and pain tolerance were higher in the frankincense and myrrha group than CYP group (P<0.05). ZO-2 expression in the bladder was increased in the CYP + pentosan polysulfate and frankincense + myrrha groups compared with the CYP-induced acute IC/PBS group (P<0.05).@*CONCLUSION@#frankincense and myrrha modulate urothelial wound healing, which ameliorates typical features of acute IC/PBS in rats.

Intravesical Glycosaminoglycans Experience for Chronic Lower Urinary Tract Pathology Treatment / Experiencia con glucosaminoglicanos intravesicales para el tratamiento de patologías crónicas del tracto urinario inferior

Objective Intravesical glycosaminoglycans (GAG) treatment is one of the therapeutic options for chronic bladder pathologies and is approved for Bladder Pain Syndrome (BPS), radiation cystitis, and recurrent urinary tract infections (UTIs). The purpose of this study is to describe the demographic characteristics of patients with such pathologies in our population and to evaluate treatment response. Methods It is a retrospective study of patients with the aforementioned pathologies, who received treatment with GAG. Demographic characteristics and subjective improvement with treatment were evaluated. A bivariate analysis was performed to study possible improvement predictors. Results 53 patients were evaluated. Of them, 33 (62.3%) with BPS, 12 (22.6%) with recurrent UTIs, and 8 (15.1%) with radiation cystitis. The dose range received was between 4 - 20 instillations, with a median of 6 doses. 67.9% of patients showed improvement of symptoms with treatment, this percentage being even higher for the group of patients with recurrent UTIs (91%). No treatment response predictors were found. Conclusions Intravesical GAG treatment is a therapeutic alternative for patients with chronic bladder pathologies, with satisfactory results in the medium term. Prospective studies are needed to support the findings of this study.

Objetivo El tratamiento con glucosaminoglicanos intravesicales hace parte de las opciones terapéuticas de las patologías crónicas de la vejiga y se encuentra aprobado para el tratamiento de síndrome de vejiga dolorosa (SVD), cistitis por radiación e infección urinaria recurrente. El objetivo de este estudio es describir las características demográficas de los pacientes con dichas patologías en nuestra población y evaluar la respuesta al tratamiento. Métodos Estudio retrospectivo de pacientes con las patologías mencionadas, quienes recibieron tratamiento con glucosaminoglicanos. Se evaluaron las características demográficas y la respuesta al tratamiento. Se realizó un análisis bivariado para estudiar posibles variables predictoras de mejoría. Resultados Se evaluaron 53 pacientes. De estos, 33 (62.3%) con síndrome de vejiga dolorosa, 12 (22.6%) con infección urinaria recurrente y 8 (15.1%) con cistitis por radiación. El rango de dosis recibida estuvo entre 4-20 instilaciones, con una mediana de 6 dosis. El 67.9% de los pacientes tuvo una respuesta adecuada al tratamiento, siendo este porcentaje aún mayor para el grupo de pacientes con IVU recurrente (91%). No se encontraron factores predictores de respuesta al tratamiento. Conclusiones El tratamiento con GAG intravesicales es una alternativa terapéutica para pacientes con patologías crónicas de la vejiga, con resultados satisfactorios a mediano plazo. Se necesitan estudios prospectivos que soporten los hallazgos de este trabajo.

Risk Factors for Interstitial Cystitis in the General Population and in Individuals With Depression / 대한배뇨장애요실금학회지

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.

Efficacy of electroacupuncture nerve stimulation therapy for interstitial cystitis/bladder pain syndrome / 中国针灸

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.

Impact of intravesical hyaluronic acid treatment on bladder inflammation in interstitial cystitis rat model

ABSTRACT Objective: To evaluate the effect of intravesical hyaluronic acid (HA) treatment on inflammatory cells and the severity of inflammation in an interstitial cystitis rat model created with hydrogen chloride (HCL) via immunohistochemical studies and myeloperoxidase activity for the first time in the literature. Materials and Methods: A total of 30 adult female white Rattus Norvegicus rats were divided into 3 groups as the HCL group, hyaluronic acid treatment (HCL-HA) group and control group. Chemical cystitis was created by administering HCL(400 microL,10 mM) except control group. A single dose of intravesical HA(0.5 mL,0.8 mg/mL) was administered to the treatment group. The bladder tissues of all subjects were immunohistochemically stained. The cell surface markers were used to evaluate inflammatory cell infiltration. Mast cell activation and IL-6 was evaluated to assess the inflammation and severity of inflammation, respectively. Myeloperoxidase activity was measured as it shows neutrophil density. Statistical significance was accepted as P<0.05. Results: It was observed that there was rich monocyte, T lymphocyte, B lymphocyte, and Natural Killer cells infiltration and high IL-6 levels in the bladder tissue after the intravesical hydrogen chloride instillation, especially in the stroma layer(p<0.005). In the HCL-HA group, severity of inflammation had statistically significantly regressed to the levels of the control group(p<0.005). An increase was observed in the bladder myeloperoxidase activity of the HCL group compared to the other two groups(p<0.05). Conclusions: Single dose intravesical hyluronic acid instillation reduces inflammatory cell infiltration and the severity of bladder inflammation in the rat model of bladder pain syndrome/interstitial cystitis.

Systematic review of oral therapy for the treatment of symptoms of bladder pain syndrome: The brazilian guidelines / Revisão sistemática sobre terapia oral para tratamento dos sintomas da síndrome da bexiga dolorosa: as diretrizes brasileiras

Abstract Interstitial cystitis (IC), including bladder pain syndrome (BPS), is a chronic and debilitating disease thatmainly affectswomen. It is characterized by pelvic pain associated with urinary urgency, frequency, nocturia and negative urine culture,with normal cytology. In 2009, the Society for Urodynamics and Female Urology (SUFU) defined the term IC/BPS as an unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms for more than 6 weeks duration, in the absence of infection or other identifiable causes. This is the definition used by the American Urological Association (AUA) in the most recent guidelines on IC/BPS. Interstitial cystitis may be sufficiently severe to have a devastating effect on the quality of life, but it may also be associated with moderate symptoms whose effects are less debilitating. Although there are several clinical trials to assess oral and intravesical therapies, the treatment for IC remains far from ideal. This systematic assessment evaluates published randomized clinical trials on oralmedications used totreat symptoms of BPS. This studywas performed according to the preferred reporting items for systematic reviews and metaanalyses (PRISMA)method. Two independent reviewers screened the studies to determine their inclusion or exclusion and to perform the methodological analysis. The inclusion criteria included randomized studiespublishedbetween April of 1988and April of2016 that used oral medications to treat symptoms of BPS or IC. According to the systematic review performed,we should consider pentosan polysulfate as one of the bestoptions of oral drugs for the treatment of BPS symptoms. However, this drug is not an available option in Brazil. Orally administered amitriptyline is an efficacious medical treatment for BPS, and it should be the first treatment offered.

Resumo Cistite intersticial (IC), incluindo a síndrome da bexiga dolorosa (SBD), é uma doença crônica e debilitante que afeta principalmente mulheres. É caracterizada por dor pélvica associada à urgência miccional, frequência urinária, noctúria e exame cultural de urina negativo, com citologia normal. A cistite intersticial pode ser suficientemente severa para ter um efeito devastador na qualidade de vida, mas também pode estar associada a sintomas moderados e menos debilitantes. Embora existam vários ensaios clínicos para avaliar terapias orais e intravesicais, o tratamento para IC permanece longe do ideal. Esta revisão sistemática avaliou ensaios clínicos randomizados publicados sobre medicamentos orais usados para tratar sintomas de SBD. Este estudo foi realizado de acordo com ométodo preferred reporting items for systematic reviews and meta-analyses (PRISMA). Dois revisores independentes examinaram os estudos para determinar sua inclusão ou exclusão e para realizar a análise metodológica. Os critérios de inclusão foram: ensaios clínicos randomizados publicados entre abril de 1988 e abril de 2016 que usaram medicações orais no tratamento dos sintomas da SBD ou CI. De acordo com a revisão sistemática realizada, a melhor opção de medicação oral para o tratamento dos SBD é o pentosano polissulfato sódico. No entanto, esta droga não está disponível no Brasil. A amitriptilina administrada por via oral é um tratamento eficaz para SBD e deve ser oferecida como primeira escolha.

Animal Modelling of Interstitial Cystitis/Bladder Pain Syndrome / 대한배뇨장애요실금학회지

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.

Differences in Urodynamic Parameters According to the Presence of a Hunner Lesion in Women With Interstitial Cystitis/Bladder Pain Syndrome / 대한배뇨장애요실금학회지

PURPOSE: Differences in the severity of subjective symptoms have been noted depending on whether a Hunner lesion is present in women with interstitial cystitis/bladder pain syndrome (IC/BPS). In this study, we aimed to identify differences in objective urodynamic parameters in women with IC/BPS according to the presence of a Hunner lesion. METHODS: This cross-sectional study included a total of 55 patients with IC/BPS. IC/BPS and the presence of a Hunner lesion on cystoscopy were diagnosed according to American Urological Association guidelines. The patients were categorized into a Hunner IC/BPS group and a non-Hunner IC/BPS group according to the presence of a Hunner lesion on cystoscopy. At the initial visit, a medical history was taken from all patients with IC/BPS, and they underwent symptom assessment using a 3-day voiding diary and laboratory tests. A urodynamic study was then performed before any treatment was performed. Baseline characteristics and urodynamic parameters were compared between the 2 groups. RESULTS: Of the 55 patients, 23 (41.8%) had a Hunner lesion on cystoscopy. As documented in the voiding diaries, the Hunner IC/BPS group had more frequent voids and a smaller maximal voided volume (P=0.045, P < 0.001, respectively). Regarding urodynamic parameters, the mean volume at the first desire to void, normal desire to void, strong desire to void (SDV), and maximum cystometric bladder capacity (MBC) was significantly lower in the Hunner IC/BPS group (P=0.001, P=0.004, P < 0.001, and P < 0.001, respectively). On receiver operating characteristic curve analysis, patients with an SDV≤210 mL (area under the curve [AUC]=0.838, P < 0.001) and an MBC≤234 mL (AUC=0.857, P < 0.001) were likely to be in the Hunner IC/BPS group. CONCLUSIONS: The differences in patients’ subjective symptoms between the Hunner IC/BPS and non-Hunner IC/BPS groups were confirmed to correspond to differences in objective urodynamic parameters.

Feline Interstitial Cystitis Enhances Mucosa-Dependent Contractile Responses to Serotonin / 대한배뇨장애요실금학회지

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.

Expression of nerve growth factor in urine of patients with interstitial cystitis and its clinical significance / 中华泌尿外科杂志

Objective Evaluate the clinical value of nerve growth factor (NGF) in patients with interstitial cystitis for diagnosis and predicting the prognostic.Methods From January 2013 to January 2017,22 cases of interstitial cystitis patients,including 20 female cases and 2 male cases,were collected.Their mean age was (48.5 ± 12.8) years old.The average frequency of urination was 25.4 ±4.6 before treatment.The average frequency of nocturia was 4.6 ± 0.5.The average maximal bladder volume was (223.4 ± 39.5)ml.Their IPSS and QOL scores were 17.3 ± 1.2,12.7 ± 1.7,respectively.Meanwhile,22 healthy volunteers,including 18 female cases and 4 male cases,were collected.Their mean age was (40.2 ± 8.7) years old.The average frequency of urination was 4.2 ± 2.6 before treatment.The average frequency of nocturia was 1.1 ± 0.4.Urine NGF of these patients were collected before and after sodium hyaluronate bladder perfusion treatment,and the levels of NGF were detected by ELISA method.The correlationship between NGF and the severity of the symptoms were evaluated before and after treatment.Results After 1,3 and 6 months' treatment,the levels of NGF were dropped from (243.5 ±37.8) ng/L to (187.3 ±28.7) ng/L,(141.5 ± 21.3) ng/L and (123.1 ± 15.9) ng/L,which was positively associated with the degree of clinical symptom.The number of urination droppted from 25.4 ± 4.6 to 21.7 ± 5.2,17.2 ± 3.9 and 14.6 ± 3.8.The number of nocturia was dropped from 4.6 ± 0.5 to 3.8 ± 0.6,3.0 ± 0.8 and 1.7 ± 1.1.The maximum volume of bladder increased from (223.4 ± 39.5) ml to (258.7 ± 40.2) ml,(289.6 ± 37.1) ml and (305.2±40.4) ml.The IPSS scores dropped from 17.3 ± 1.2 to 15.1 ±2.4,12.4 ± 1.82and 9.8 ± 1.4.The QOL scores dropped from 12.7 ± 1.7 to 10.6 ± 1.2,8.5 ± 1.5 and 7.1 ± 1.3 (P ＜ 0.05).The logistic regression analysis showed the level of NGF in IC patients has positive relationship with frequency of urination,nocturia,QOL scores,IPSS scores and maximal bladder volume (P ＜ 0.05).Conclusions The level of NGF in urine is associated with IC symptom severity and NGF has the potential to be used as a marker for the diagnosis of IC.

Factors influencing the effect of first stage treatment of sacral neuromodulation / 中华泌尿外科杂志

Objective To explore the factors affecting the effect of first stage treatment of sacral neuromodulation.Methods A retrospective analysis of 39 patients with dysuria related diseases from April 2012 to January 2016 was performed.There were 14 male patients and 25 female patients.Their age ranged from 15 to 86 years old,mean 54 years old.The types of disease were bladder pain syndrome/interstitial cystitis in 1 8 cases,idiopathic urinal retention in 5 cases,overactive bladder in 8 cases,neurogenic bladder in 6 cases,and urgent incontinence in 2 cases.All patients were treated by behavioral therapy,drug therapy,and at least one recomnended treatment method.All previons treatments were ineffective.All patients were collected baseline medical records.The voiding diary,visual analogue pain score,quality of life score,anxiety score and other information before and after the first stage surgery and the last follow-up after the second stage surgery were also collected.Results A total of 39 patients were enrolled in this study.27 patients (69％)who were satisfied with the effect of the first stage of surgery were treated with the second stage surgery,and 12 patients (31％)who were not satisfied with the results of the first phase operation did not undergo the second phase operation.The second stage implantation rate was 69％.The average experience time was (21.6 ± 3.0) days.In the single first stage implantation group,there were 6 males and 6 females,including interstitial cystitis in 3 cases,overactive bladder in 3 cases,neurogenic bladder in 4 cases,idiopathic urinary retention in 1 cases and urgent incontinence in 1 cases.2 cases have a history of pelvic and urinary surgery and 10 cases dont.The average BMI was 21.8 ± 3.7 kg/m2,and mean age was(44.5 ± 19.1) years old.The average preoperative anxiety score was 33.7 ± 5.3 and the average pain score of preoperative was 8.0 ± 1.0.The average quality of life score was 4.6 ±0.8 and the average daily nunber of urine was 23.1 ± 12.8.The average mean urine volume was (89.4 ± 33.0) ml,the average frequency of nocturia was 10.3 ± 5.5,the average medical history time was (100.6 ± 125.5) months.In the second stage implantation group,there were 8 males and 19 females,including interstitial cystitis in 15 cases,overactive bladder in 5 cases,neurogenic bladder in 2 cases,idiopathic urinary retention in 4 cases,and urgent incontinence in 1 cases.10 cases have a history of pelvic and urinary surgery while 17 cases don't.Average BM1 was (24.1 ± 2.6) kg/m2,and mean age was(57.9 ± 16.8) years old.The average preoperative anxiety score was 27.7 ± 5.9,the average pain score of preoperative was 7.9 ± 1.6.The average quality of life score was 5.3 ± 0.9 the average daily urinary number was 30.6 ± 14.2.The average mean urine volume was (64.8 ± 37.4) ml and the average frequency of nocturia was 13.3 ± 9.2.The average history of time was (83.0 ± 56.0) months.Patients who were implanted with permanent sacral neuromodulation system were mostly older (P =0.034),with higher BMI (P =0.043) and lower anxiety (P =0.008).There were no statistically significant differences in gender(P =0.287),disease(P =0.116),the daily urinary frequency (P =0.140),the average urine volume (P =0.470),nocturia freqnency (P =0.068),pain scores (P =0.880),surgical history (P =0.276)and the medical history time (P =0.116) between patients who underwent first stage surgery only and second stage surgery.Conclusion BMI,age and anxiety may be the factors that affect the outcome of the first stage treatment of sacral neuromodulation.

The function and mechanism of NALP3 inflammasome in interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective To acknowledge the NALP3 inflammasome expression and significance in the interstitial cystitis/bladder pain syndrome (IC/PBS).Methods The urine of 16 IC/BPS patients and 16 normal persons was collected to measure the IL-1β content by ELISA.Bladder tissue of 16 IC/BPS patients and para-carcinoma tissue of 16 bladder cancer patients were collected.And the levels of NALP3,caspase1 and IL-1β were detected by Western Blot.60 female rats were randomly divided into control group(bladder was infused with 0.5 ml saline),hyaluronidase group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml)],NALP3 antagonist group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml) and Glyburide(10 mg/kg)] and mucosal protectant group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml) and sodium hyaluronate(0.8 mg/ml)] to carried out the animal experiment,and 15 rats in each group.The models were created by long-term (1 month) intermittent intravesical hyaluronidase infusion.Voiding patterns were investigated by cystometry.Toluidine blue staining was used to detected mast cell’s changes.The levels of NALP3,caspase-1 and IL-1β were determined by Western Blot,HE staining was to detect tissue inflammation of the bladder,and the severity of pain was examined by Von-frey brush by using the strength of 0.07、0.4、1.0 g.The comparison between the chemotaxis of 200 ng,400 ng IL-1β and 200ng SCF IL-1β to mast cells was checked by Transwell experiment.Results The expressions of IL-1β in IC/PBS patients was increased in IC/PBS group than normal control group [(381 ± 112) μg/L vs.(98 ± 40) μg/L,P ＜0.01].The expressions of NALP3,Caspase-1 and IL-lβ had increased in the IC/PBS group than normal group(0.22 ±0.08 vs.0.11 ±0.02,0.25 ±0.03 vs.0.10 ±0.01,0.19 ±0.04 vs.0.11 ± 0.02,P ＜ 0.05)by Western Blot.In the IC/PBS rats,compared with the control group,the intercontraction intervals [(120.0 ± 15.6) s vs.(447.3 ± 24.6) s] and bladder capacity [(0.34 ± 0.02) ml vs.(1.33 ± 0.04) ml] of the model group were significantly decreased (both P ＜ 0.05).In mucosal protectant group and NALP3 antagonist group,the intercontraction intervals [(323 ± 16.3)s,(280 ± 12.5)s] and bladder capacity [(1.14 ± 0.05) ml,(0.84 ± 0.04) ml] were increased compared with control group (P ＜ 0.05).The amount of mast cell in model group were significantly increased than control group (3.4 ±0.8 vs.0.4 ± 0.2,P ＜ 0.05) while in mucosal protectant group (1.8 ± 0.5) and NALP3 antagonist group (1.5 ± 0.7) were decreased compared with control group (P ＜ 0.05).The protein levels in modle group of NALP3 (5.91 ±0.33 vs.1.00 ±0.12),caspase-1 (6.75 ±0.42 vs.1.00 ±0.22) and IL-1β(7.12 ±0.45 vs.1.00 ± 0.18)were increased than control group.In mucosal protectant group and NALP3 antagonist group,theNALP3 (2.921 ±0.21,2.07±0.18),caspase-1 (3.28 ±0.31,2.25 ±0.19) and IL-1β(3.33± 0.41,1.98 ±0.21) were decreased compared with control group.VonFrey pain score in model group were significantly increased than control group(0.07 g:7.5 ± 1.8 vs.2.1 ± 0.5,0.4 g:9.2 ± 1.9 vs.5.2 ± 1.1,1.0g:15.4±3.8 vs.6.8±1.5,P＜0.05) and VonFrey pain score(0.07 g:2.4±0.3,2.8± 0.7;0.4 g:5.2 ±0.4,6.5 ±1.3;1.0 g:6.4 ±0.8,7.3 ±1.1;P＜0.05) in NALP3 antagonist group were significantly decreased.In vitro,Transwell experimental results showed that 400 ng IL-1β of mast cell chemotaxis is similar with that of the 200 ng SCF (3 800 ±400 vs.4 800 ±500,P ＞0.05).Conclusions The levels of NALP3/Caspase-1/IL-1β in the urine of patients with IC/PBS were significantly higher than those in normal control group.NALP3 is activated in chronic cystitis rat model,and related to pain and frequent urination.This may be related to the down-regulation of expression of NALP3,caspase-1,IL-1β,and other inflammatory mediators,and blocking the chemotactic effects of IL-1 β on mast cells.

Expression and clinical significance of mast cells and related immune factors in interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective To investigate the significance of mast cells activation,and IL-6,IL-10,sialic acid-binding immunoglobulin-like lectins 8 (Siglec-8) expression in interstitial cystitis/bladder pain syndrome.Methods Bladder mucosal biopsy tissues of 21 patients with IC/BPS admitted to our hospital from March 2016 to October 2017 were taken as the IC/BPS group,and normal bladder mucosa biopsy tissues of 9 patients who underwent ureteroscopy were taken as the control group.In the IC/BPS group,there were 3 males and 18 females aged (56.2 ± 3.4) years,and the patients'pain symptom score (PUF) was (24.6 ± 3.6).Four males and five females in the control group were aged (63 ± 5.1) years.The infiltration of bladder mucosa mast cells and plasma cells in IC/BPS group and control group was observed by transmission electron microscopy.The expression of IL-6,IL-10 and Siglec-8 were detected by immunohistochemical staining.The relationship between the expression level of the immune index and the PUF score was analyzed.Results In the IC/BPS group,mast cells and plasma cells was observed in 18 of the 21 cases,but no mast cells or plasma cells were observed in the control group.Expression of IL-6 in IC/BPS group 1 case (-),11 cases(+) and 9 cases (+ +).IL-6 expression in the control group 9 cases were all (-).The difference of IL-6 expression between the IC/BPS group and the control group was statistically significant (P =0.001).Expression of IL-10 were 3 cases (-),7 cases (+ +),11 cases (+ +) in IC/BPS group,while 7 cases (-),2 cases (+ +),and 0 cases (+ +)in the control group,and there was significant difference between the two group (P =0.001).In the IC/BPS group,expression of Siglee-8 were 12 cases (-),5 (+),4 (+ +),while in control group 7 cases (-),2 (+),and 0 (+ +),no statistically significant difference was found between the two group (P =0.214).The PUF score of the patients with IL-10 expression (-) was 19.7 ± 2.1,lower than those with IL-10 (+ +) (27.1 + 2.5,P ＜ 0.001).PUF of patients with IL-10 (+) was 22.7 ± 1.8,lower than those with (+ +) (P =0.001).The PUF score of IL-6 expression (-) was 21.The PUF score of IL-6 expression (+) was (23.2 + 3.2),lower than (+ +) (26.7 + 3.1,P =0.025).The PUF score of (+ +) IC/BPS patients was (26.6 ± 2.4),higher than that of (+) IC/BPS patients (21.5 ± 2.1,P ＜ 0.0 l).The PUF score of Siglec-8 expression (+ +) and (+) in IC/BPS group was (21.3 ± 2.0),lower than that of Siglec-8 (-) (27.0 ± 2.3,P ＜ 0.0l).Conclusions Mast cells and plasma cells were expressed in IC/BPS tissues.The expression of IL-6 and IL-10 was positively correlated with clinical symptoms,while the expression of Siglec-8 was negatively correlated with clinical symptoms.

Neonatal Bladder Irritation Is Associated With Vanilloid Receptor TRPV1 Expression in Adult Rats / 대한배뇨장애요실금학회지

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.

Intravesical injection of botulinum toxin A for treatment of interstitial cystitis/bladder pain syndrome: 13 years of experience / 中华泌尿外科杂志

Objective To evaluate the efficacy of the intravesical injection of botulinum toxin A (BTX-A) and bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods We retrospectively reviewed 153 women with IC/BPS from January 2003 to December 2015.Of the 153 patients,77 were treated with BTX-A(group A),the average age was (56.0 ± 4.1) years old.76 underwent bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation (group B),the average age was (58.0 ± 3.3) years old.The patients were evaluated using the O'Leafy-Saint score,visual analog scale pain score,urinary frequency record and quality of life questionnaire before treatment and 1 week,1,3,6 and 12 months after treatment.Results In group A,only 2 had acute urinary retention,27 received a repeat injection,and 28 were lost to follow-up.In group B,3 had urinary tract infection,15 switched to BTX-A injection at 6 months because the treatment of hydrodistention plus Cystistat instillation is not good.31 were lost to follow-up.BTX-A was shown to remain effective for up to 6 months after treatment.After repeated Chinese BTX-A injections,symptoms improved significantly.Hydrodistention plus Cystistat remained effective for up to 3 months after treatment.Conclusions Intravesical injection of BTX-A is a effective therapeutic option for patients with IC/BPS.The average duration of the effect of one dose of Chinese BTX-A was 6 months.Repeated injection of BTX-A is effective.