Die Dysregulation von Neurotransmittersystemen spielt eine wesentliche Rolle für die Pathophysiologie des Bladder Pain Syndrom/Interstitielle Zystitis (BPS/IC). Diese Arbeit beschäftigt sich daher mit der veränderten Expression muskarinerger (M2, M3) und purinerger (P2X1, P2X2, P2X3) Rezeptoren auf Urothelzellen und suburothelialen Myofibroblasten der Harnblasenwand im Rahmen BPS/IC. Dazu wurde eine Gruppe von Patientinnen mit Verdacht auf BPS/IC (n=17) einer Kontrollgruppe (n=7) gegenübergestellt. Die Gewebeproben der Patientengruppe sind im Zuge der Basisdiagnostik (transurethrales Harnblasenmapping) bei klinischem Verdacht auf das Vorliegen eines BPS/IC entnommen worden. Das Gewebe der Kontrollgruppe entstammt makroskopisch unauffälligen Bereichen von Harnblasen, welche im Rahmen einer radikalen Zystektomie oder einer lateral erweiterten endopelvinen Resektion (LEER-OP) entnommen worden sind. Die semi-quantitative Analyse der Rezeptorexpression erfolgte mittels indirekter Immunfluoreszenz, die Auswertung erfolgte mittels konfokaler Laserscanningmikroskopie. Die Ergebnisse der Patientengruppe wurden mit denen der Kontrollgruppe verglichen. Im Rahmen dessen wurde auch ein individuelles Rezeptorprofil für jeden Patienten erstellt. Es zeigte sich eine Hochregulation von M2R, M3R und P2X1R auf Urothelzellen sowie eine Hochregulation von M2R, M3R, P2X1R und P2X2R auf suburothelialen Myofibroblasten in der BPS/IC-Gruppe im Vergleich zur Kontrollgruppe. Des Weiteren zeigten sich individuelle Unterschiede in den Rezeptorprofilen der Patienten. Die Ergebnisse werden vor dem Hintergrund einer möglichen Beteiligung der Regulation von muskarinergen und purinergen Rezeptoren an der Pathophysiologie des BPS/IC diskutiert. Ferner werden diagnostische und therapeutische Möglichkeiten einer erweiterten Mollekulardiagnostik diskutiert.

Die Dysregulation von Neurotransmittersystemen spielt eine wesentliche Rolle für die Pathophysiologie des Bladder Pain Syndrom/Interstitielle Zystitis (BPS/IC). Diese Arbeit beschäftigt sich daher mit der veränderten Expression muskarinerger (M2, M3) und purinerger (P2X1, P2X2, P2X3) Rezeptoren auf Urothelzellen und suburothelialen Myofibroblasten der Harnblasenwand im Rahmen BPS/IC. Dazu wurde eine Gruppe von Patientinnen mit Verdacht auf BPS/IC (n=17) einer Kontrollgruppe (n=7) gegenübergestellt. Die Gewebeproben der Patientengruppe sind im Zuge der Basisdiagnostik (transurethrales Harnblasenmapping) bei klinischem Verdacht auf das Vorliegen eines BPS/IC entnommen worden. Das Gewebe der Kontrollgruppe entstammt makroskopisch unauffälligen Bereichen von Harnblasen, welche im Rahmen einer radikalen Zystektomie oder einer lateral erweiterten endopelvinen Resektion (LEER-OP) entnommen worden sind. Die semi-quantitative Analyse der Rezeptorexpression erfolgte mittels indirekter Immunfluoreszenz, die Auswertung erfolgte mittels konfokaler Laserscanningmikroskopie. Die Ergebnisse der Patientengruppe wurden mit denen der Kontrollgruppe verglichen. Im Rahmen dessen wurde auch ein individuelles Rezeptorprofil für jeden Patienten erstellt. Es zeigte sich eine Hochregulation von M2R, M3R und P2X1R auf Urothelzellen sowie eine Hochregulation von M2R, M3R, P2X1R und P2X2R auf suburothelialen Myofibroblasten in der BPS/IC-Gruppe im Vergleich zur Kontrollgruppe. Des Weiteren zeigten sich individuelle Unterschiede in den Rezeptorprofilen der Patienten. Die Ergebnisse werden vor dem Hintergrund einer möglichen Beteiligung der Regulation von muskarinergen und purinergen Rezeptoren an der Pathophysiologie des BPS/IC diskutiert. Ferner werden diagnostische und therapeutische Möglichkeiten einer erweiterten Mollekulardiagnostik diskutiert.

The aim of this thesis is to investigate the prevalence and management of bladder pain syndrome (BPS) amongst women with chronic pelvic pain (CPP) through a series of systematic reviews, a structured survey and primary study. It has been acknowledged that the diagnosis and management of BPS is a contentious subject. The mean prevalence of BPS in women with CPP is 61%. I initially carried out a patient and clinician survey to understand how BPS was being managed in the UK. I found wide variation in diagnostic methods and treatments of BPS used by clinicians and experienced by patients with no obvious consensus. Since we know the predominant complaint in these patients is pain (bladder or pelvic) I used patients with pelvic pain as my cohort. Cystoscopy is no longer used as a diagnostic test for BPS. It is possible to diagnose BPS through a consensus expert panel using symptom-based criteria. This method of deriving a reference standard is demonstrated in the primary study, since no gold standard diagnostic test exists for BPS. A case-control feasibility study was undertaken to investigate the accuracy of a group of urinary symptoms to diagnose BPS. While, neither index test of bladder filling pain or bladder wall tenderness can sensitively diagnose BPS alone, the symptoms of bladder filling pain, urinary frequency, pain on urination and pain on full bladder are a good predictor of the condition. A systematic review assessing the reporting outcomes identified five measures that should be included in studies; pain, urinary symptoms, general 8 wellbeing, quality of life and bladder capacity. Of the 19 treatments used for BPS, the level and strength of evidence ratings overestimated quality compared to the GRADE ratings. BPS can be diagnosed symptomatically but there is variable reporting of outcome measures and poor evidence for treatment effectiveness.

Yes / The aim of this study was to assess the feasibility of a randomized controlled trial (PFM) treatment in women with bladder pain syndrome (BPS). Prolonged PFM tension contributes to the bladder pain, urinary frequency and urgency associated with BPS. Pelvic health physiotherapists routinely provide intravaginal myofascial release (MFR) to the PFMs in order to effectively reduce symptoms. Rapid access A TW was designed so as to allow men with chronic pelvic pain to self- treat, and this may be effective in women with BPS. For 6 weeks, two groups received weekly physiotherapist- provided MFR, and were monitored for a further 6- week follow- up period. One group also used a TW at home three times a week throughout the pilot. Weekly outcome measures of BPS symptoms and quality of life were recorded. A clinically meaningful difference in Interstitial Cystitis Symptoms Index and Interstitial Cystitis Problem Index score changes between groups was group = 6.20 ± 0.83 and 5.00 ± 1.41, respectively), and a difference was observed during the follow- up period (control group = 4.50 ± 1.73 and 4.00 ± 2.44, respecevents. Using the TW appears to have enhanced physiotherapy treatment during the initial 6 weeks, and improved symptoms during the 6- week follow- up period. The TW may be a clinically useful tool for long- term management of BPS. The feasibility of the study method was proven, some alterations were recommended and an RCT is now warranted.

Die Dysregulation von Neurotransmittersystemen spielt eine wesentliche Rolle für die Pathophysiologie des Bladder Pain Syndrom/Interstitielle Zystitis (BPS/IC). Diese Arbeit beschäftigt sich daher mit der veränderten Expression muskarinerger (M2, M3) und purinerger (P2X1, P2X2, P2X3) Rezeptoren auf Urothelzellen und suburothelialen Myofibroblasten der Harnblasenwand im Rahmen BPS/IC. Dazu wurde eine Gruppe von Patientinnen mit Verdacht auf BPS/IC (n=17) einer Kontrollgruppe (n=7) gegenübergestellt. Die Gewebeproben der Patientengruppe sind im Zuge der Basisdiagnostik (transurethrales Harnblasenmapping) bei klinischem Verdacht auf das Vorliegen eines BPS/IC entnommen worden. Das Gewebe der Kontrollgruppe entstammt makroskopisch unauffälligen Bereichen von Harnblasen, welche im Rahmen einer radikalen Zystektomie oder einer lateral erweiterten endopelvinen Resektion (LEER-OP) entnommen worden sind. Die semi-quantitative Analyse der Rezeptorexpression erfolgte mittels indirekter Immunfluoreszenz, die Auswertung erfolgte mittels konfokaler Laserscanningmikroskopie. Die Ergebnisse der Patientengruppe wurden mit denen der Kontrollgruppe verglichen. Im Rahmen dessen wurde auch ein individuelles Rezeptorprofil für jeden Patienten erstellt. Es zeigte sich eine Hochregulation von M2R, M3R und P2X1R auf Urothelzellen sowie eine Hochregulation von M2R, M3R, P2X1R und P2X2R auf suburothelialen Myofibroblasten in der BPS/IC-Gruppe im Vergleich zur Kontrollgruppe. Des Weiteren zeigten sich individuelle Unterschiede in den Rezeptorprofilen der Patienten. Die Ergebnisse werden vor dem Hintergrund einer möglichen Beteiligung der Regulation von muskarinergen und purinergen Rezeptoren an der Pathophysiologie des BPS/IC diskutiert. Ferner werden diagnostische und therapeutische Möglichkeiten einer erweiterten Mollekulardiagnostik diskutiert.:Bibliografische Angaben 4 Abkürzungsverzeichnis 6 1. Einleitung 8 1.1. Das Bladder Pain Syndrom 8 1.1.1. Definition 8 1.1.2. Epidemiologie 10 1.1.3. Ätiologie und Pathophysiologie 10 1.1.4. Diagnostik 13 1.1.5. Therapie 16 1.2. Anatomische und physiologische Grundlagen 20 1.2.1. Das Urothel 21 1.2.2. Lamina propria 22 1.2.3. Muskarinerge Acetylcholinrezeptoren 23 1.2.4. Purinerge Rezeptoren 27 1.3. Fragestellung und Zielsetzung 31 2. Material und Methoden 32 2.1. Material 32 2.2. Methoden 33 2.2.1. Immunhistologie 33 2.2.2. Konfokale Laserscanning Mikroskopie und Auswertung 33 3. Ergebnisse 37 3.1. Lichtmikroskopie 37 3.2. Laserscanningmikroskopie 40 3.2.1. Rezeptorexpression im Urothel 40 3.2.2. Statistischer Vergleich von Kontroll-und BPS/IC-Gruppe im Urothel 42 3.2.4. Statistischer Vergleich von Kontroll-und BPS/IC-Gruppe auf sMF 46 3.2.5. Rezeptorprofile von Urothelzellen und sMF 47 3.3. Zusammenfassung 52 4. Diskussion 53 4.1. Diagnostisches Dilemma 53 4.2. Rezeptorverteilung im Urothel 61 4.3. Rezeptorverteilung auf sMF 64 4.4. Diagnostische und therapeutische Möglichkeiten des Rezeptorprofiling 65 4.5. Methodik der vorliegenden Arbeit 69 4.7. Zusammenfassung 71 Anhang 73 Referenzen 75 Erklärung über die eigenständige Abfassung der Arbeit 84

Die Dysregulation von Neurotransmittersystemen spielt eine wesentliche Rolle für die Pathophysiologie des Bladder Pain Syndrom/Interstitielle Zystitis (BPS/IC). Diese Arbeit beschäftigt sich daher mit der veränderten Expression muskarinerger (M2, M3) und purinerger (P2X1, P2X2, P2X3) Rezeptoren auf Urothelzellen und suburothelialen Myofibroblasten der Harnblasenwand im Rahmen BPS/IC. Dazu wurde eine Gruppe von Patientinnen mit Verdacht auf BPS/IC (n=17) einer Kontrollgruppe (n=7) gegenübergestellt. Die Gewebeproben der Patientengruppe sind im Zuge der Basisdiagnostik (transurethrales Harnblasenmapping) bei klinischem Verdacht auf das Vorliegen eines BPS/IC entnommen worden. Das Gewebe der Kontrollgruppe entstammt makroskopisch unauffälligen Bereichen von Harnblasen, welche im Rahmen einer radikalen Zystektomie oder einer lateral erweiterten endopelvinen Resektion (LEER-OP) entnommen worden sind. Die semi-quantitative Analyse der Rezeptorexpression erfolgte mittels indirekter Immunfluoreszenz, die Auswertung erfolgte mittels konfokaler Laserscanningmikroskopie. Die Ergebnisse der Patientengruppe wurden mit denen der Kontrollgruppe verglichen. Im Rahmen dessen wurde auch ein individuelles Rezeptorprofil für jeden Patienten erstellt. Es zeigte sich eine Hochregulation von M2R, M3R und P2X1R auf Urothelzellen sowie eine Hochregulation von M2R, M3R, P2X1R und P2X2R auf suburothelialen Myofibroblasten in der BPS/IC-Gruppe im Vergleich zur Kontrollgruppe. Des Weiteren zeigten sich individuelle Unterschiede in den Rezeptorprofilen der Patienten. Die Ergebnisse werden vor dem Hintergrund einer möglichen Beteiligung der Regulation von muskarinergen und purinergen Rezeptoren an der Pathophysiologie des BPS/IC diskutiert. Ferner werden diagnostische und therapeutische Möglichkeiten einer erweiterten Mollekulardiagnostik diskutiert.:Bibliografische Angaben 4 Abkürzungsverzeichnis 6 1. Einleitung 8 1.1. Das Bladder Pain Syndrom 8 1.1.1. Definition 8 1.1.2. Epidemiologie 10 1.1.3. Ätiologie und Pathophysiologie 10 1.1.4. Diagnostik 13 1.1.5. Therapie 16 1.2. Anatomische und physiologische Grundlagen 20 1.2.1. Das Urothel 21 1.2.2. Lamina propria 22 1.2.3. Muskarinerge Acetylcholinrezeptoren 23 1.2.4. Purinerge Rezeptoren 27 1.3. Fragestellung und Zielsetzung 31 2. Material und Methoden 32 2.1. Material 32 2.2. Methoden 33 2.2.1. Immunhistologie 33 2.2.2. Konfokale Laserscanning Mikroskopie und Auswertung 33 3. Ergebnisse 37 3.1. Lichtmikroskopie 37 3.2. Laserscanningmikroskopie 40 3.2.1. Rezeptorexpression im Urothel 40 3.2.2. Statistischer Vergleich von Kontroll-und BPS/IC-Gruppe im Urothel 42 3.2.4. Statistischer Vergleich von Kontroll-und BPS/IC-Gruppe auf sMF 46 3.2.5. Rezeptorprofile von Urothelzellen und sMF 47 3.3. Zusammenfassung 52 4. Diskussion 53 4.1. Diagnostisches Dilemma 53 4.2. Rezeptorverteilung im Urothel 61 4.3. Rezeptorverteilung auf sMF 64 4.4. Diagnostische und therapeutische Möglichkeiten des Rezeptorprofiling 65 4.5. Methodik der vorliegenden Arbeit 69 4.7. Zusammenfassung 71 Anhang 73 Referenzen 75 Erklärung über die eigenständige Abfassung der Arbeit 84 Lebenslauf: 85 Danksagung: 86

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a disabling chronic disease of still unknown origin and complex pathophysiology. The disease affects mainly female patients, with a female to male ratio of about 9 to 1. Prevalence ranges from 52 to 500/100,000 in females and 8 to 41/100,000 in males. The diagnosis of IC/BPS is mainly hampered by the lack of appropriate biomarkers and, therefore, extensive clinical examinations are required to exclude “confusable” diseases [1]. In consequence, most patients experience several years of ineffective treatments of various urinary tract symptoms often associated with, but by themselves not characteristic of, IC/BPS. Unequivocal diagnosis of IC/BPS is the prerequisite to find more effective therapeutic approaches. Therefore, more specific biomarkers are needed to facilitate IC/BPS diagnosis and to stratify patients for treatment at earlier stages of the disease. In this Special Issue, we gathered reviews and original work elucidating the current developments in IC/BPS biomarker research.

In this review, we focused on putatively interesting biomarkers of interstitial cystitis/bladder pain syndrome (IC/BPS) in relation to the etiopathology of this disease. Since its etiopathology is still under discussion, the development of novel biomarkers is critical for the correct classification of the patients in order to open personalized treatment options, on the one hand, and to separate true IC/BPS from the numerous confusable diseases with comparable symptom spectra on the other hand. There is growing evidence supporting the notion that the classical or Hunner-type IC (HIC) and the non-Hunner-type IC (NHIC) are different diseases with different etiopathologies and different pathophysiology at the full-blown state. While genetic alterations indicate close relationship to allergic and autoimmune diseases, at present, the genetic origin of IC/BPS could be identified. Disturbed angiogenesis and impairment of the microvessels could be linked to altered humoral signaling cascades leading to enhanced VEGF levels which in turn could enhance leucocyte and mast cell invasion. Recurrent or chronic urinary tract infection has been speculated to promote IC/BPS. New findings show that occult virus infections occurred in most IC/BPS patients and that the urinary microbiome was altered, supporting the hypothesis of infections as major players in IC/BPS. Environmental and nutritional factors may also influence IC/BPS, at least at a late state (e.g., cigarette smoking can enhance IC/BPS symptoms). The damage of the urothelial barrier could possibly be the result of many different causality chains and mark the final state of IC/BPS, the causes of this development having been introduced years ago. We conclude that the etiopathology of IC/BPS is complex, involving regulatory mechanisms at various levels. However, using novel molecular biologic techniques promise more sophisticated analysis of this pathophysiological network, resulting in a constantly improvement of our understanding of IC/BPS and related diseases.

IINTRODUÇÃO: A Cistite Intersticial (CI) ou Síndrome da Bexiga Dolorosa (SBD) é uma síndrome crônica caracterizada pela presença de dor ou desconforto vesical ou pélvico e sintomas miccionais como urgência e aumento da frequência miccional diurna e noturna, na ausência de outra afecção identificável que justifique esses sintomas. Não existe até o momento nenhum teste diagnóstico ou marcador que defina a CI. Desta forma seu diagnóstico é predominantemente clínico, baseado nos sinais e sintomas e dependente da exclusão de outras doenças urológicas. A dificuldade no diagnóstico e no tratamento dessas pacientes reflete o pouco que se sabe sobre sua fisiopatologia e sobre as alterações genéticas presentes na doença. A identificação de marcadores pode proporcionar um melhor entendimento e manejo desses aspectos da síndrome. Na tentativa de identificar marcadores genéticos que possam estar associados a CI, avaliamos a presença de alguns polimorfismos genéticos, os polimorfismos de nucleotídeo único (SNP), no DNA de pacientes com os critérios diagnósticos de CI e comparamos sua prevalência entre as pacientes e também com um grupo controle representativo da população geral. A correlação desses polimorfismos considerando a CI e a intensidade de dor nessas pacientes ainda não foi estudada na literatura. OBJETIVOS: Analisar a presença de polimorfismos (SNP) em amostras de sangue de pacientes com CI e correlacionar a presença dos polimorfismos com o quadro de dor crônica. MÉTODOS: Foram selecionadas 34 pacientes do sexo feminino com diagnóstico de CI de acordo com os critérios do NIDDK e 23 pacientes do grupo controle (mulheres saudáveis apenas com incontinência urinária de esforço). As pacientes com o diagnóstico de CI foram estratificadas em dois grupos de acordo com o grau dos sintomas de dor crônica. Foram selecionados 20 polimorfismos para análise: rs1800871, rs1800872, rs1800896, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, rs6746030. A genotipagem foi realizada através da técnica de PCR em tempo real (q-PCR) e correlacionada com o diagnóstico de CI e com a intensidade dos sintomas álgicos. RESULTADOS: O alelo polimórfico (T) do SNP rs11127292 foi mais frequente nas pacientes com CI em relação ao grupo controle (p:0,01). O alelo polimórfico (T) do SNP rs6311 foi significativamente mais frequente nas pacientes com dor mais intensa (p:0,03). A frequência do alelo selvagem (A) do SNP rs1799971 foi maior em pacientes com dor leve a moderada (p:0,04). CONCLUSÕES: Foram identificadas algumas diferenças na frequência dos polimorfismos nas pacientes estudadas, o que sugere a existência de um papel relevante dos SNP associados tanto à CI quando na intensidade dos sintomas de dor crônica nestas pacientes / INTRODUCTION: Interstitial cystitis (IC) or painful bladder syndrome (PBS) is a chronic syndrome characterized by the presence of bladder/pelvic pain or discomfort and voiding symptoms such as urgency and increased urinary waking and night-time frequency in the absence of another identifiable cause to justify these symptoms. So far, there is no diagnostic test or marker to establish the presence of IC. Thus, the diagnosis is predominantly clinical, based on signs and symptoms and dependent on the exclusion of other urological diseases. The difficulty in the diagnosis and treatment of these patients reflects the little that is known about IC physiopathology and about the genetic background of the disease. The identification of new markers may provide a better understanding and management of the syndrome. As an attempt to identify genetic markers that may be associated with IC, we evaluated the presence of some genetic polymorphisms, single nucleotide polymorphisms (SNPs), in the DNA of patients with the diagnostic criteria of IC, and we compared their prevalence among IC patients and with a control group representative of the general population. The correlation of these polymorphisms considering IC and pain intensity in these patients has not been studied in the literature. OBJECTIVES: To assess the presence of polymorphisms (SNPs) in blood samples from IC patients and to correlate the presence of polymorphisms with chronic pain. METHODS: Thirty-four female patients with a diagnosis of IC according to the NIDDK criteria and 23 control subjects (healthy women with stress urinary incontinence) were selected. Patients with the diagnosis of IC were stratified into two groups according to the degree of symptoms of chronic pain. We selected 20 polymorphisms for analysis: rs1800871, rs1800876, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, rs6746030. Genotyping was performed using the real-time PCR technique (q-PCR) and correlated with the diagnosis of IC and intensity of pain symptoms. RESULTS: The polymorphic allele (T) of the SNP rs11127292 occurred with more frequency in patients with IC compared to the control group (p= 0.01). The polymorphic allele (T) of SNP rs6311 occurred with more frequency in patients with severe pain (p= 0.03). The frequency of wild-type (A) SNP rs1799971 was higher in patients with mild to moderate pain (p= 0.04). CONCLUSION: The results indicated differences in polymorphism frequency in the patients studied, suggesting the existence of a relevant role of SNPs associated with both IC and intensity of chronic pain symptoms in these patients

IINTRODUÇÃO: A Cistite Intersticial (CI) ou Síndrome da Bexiga Dolorosa (SBD) é uma síndrome crônica caracterizada pela presença de dor ou desconforto vesical ou pélvico e sintomas miccionais como urgência e aumento da frequência miccional diurna e noturna, na ausência de outra afecção identificável que justifique esses sintomas. Não existe até o momento nenhum teste diagnóstico ou marcador que defina a CI. Desta forma seu diagnóstico é predominantemente clínico, baseado nos sinais e sintomas e dependente da exclusão de outras doenças urológicas. A dificuldade no diagnóstico e no tratamento dessas pacientes reflete o pouco que se sabe sobre sua fisiopatologia e sobre as alterações genéticas presentes na doença. A identificação de marcadores pode proporcionar um melhor entendimento e manejo desses aspectos da síndrome. Na tentativa de identificar marcadores genéticos que possam estar associados a CI, avaliamos a presença de alguns polimorfismos genéticos, os polimorfismos de nucleotídeo único (SNP), no DNA de pacientes com os critérios diagnósticos de CI e comparamos sua prevalência entre as pacientes e também com um grupo controle representativo da população geral. A correlação desses polimorfismos considerando a CI e a intensidade de dor nessas pacientes ainda não foi estudada na literatura. OBJETIVOS: Analisar a presença de polimorfismos (SNP) em amostras de sangue de pacientes com CI e correlacionar a presença dos polimorfismos com o quadro de dor crônica. MÉTODOS: Foram selecionadas 34 pacientes do sexo feminino com diagnóstico de CI de acordo com os critérios do NIDDK e 23 pacientes do grupo controle (mulheres saudáveis apenas com incontinência urinária de esforço). As pacientes com o diagnóstico de CI foram estratificadas em dois grupos de acordo com o grau dos sintomas de dor crônica. Foram selecionados 20 polimorfismos para análise: rs1800871, rs1800872, rs1800896, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, rs6746030. A genotipagem foi realizada através da técnica de PCR em tempo real (q-PCR) e correlacionada com o diagnóstico de CI e com a intensidade dos sintomas álgicos. RESULTADOS: O alelo polimórfico (T) do SNP rs11127292 foi mais frequente nas pacientes com CI em relação ao grupo controle (p:0,01). O alelo polimórfico (T) do SNP rs6311 foi significativamente mais frequente nas pacientes com dor mais intensa (p:0,03). A frequência do alelo selvagem (A) do SNP rs1799971 foi maior em pacientes com dor leve a moderada (p:0,04). CONCLUSÕES: Foram identificadas algumas diferenças na frequência dos polimorfismos nas pacientes estudadas, o que sugere a existência de um papel relevante dos SNP associados tanto à CI quando na intensidade dos sintomas de dor crônica nestas pacientes / INTRODUCTION: Interstitial cystitis (IC) or painful bladder syndrome (PBS) is a chronic syndrome characterized by the presence of bladder/pelvic pain or discomfort and voiding symptoms such as urgency and increased urinary waking and night-time frequency in the absence of another identifiable cause to justify these symptoms. So far, there is no diagnostic test or marker to establish the presence of IC. Thus, the diagnosis is predominantly clinical, based on signs and symptoms and dependent on the exclusion of other urological diseases. The difficulty in the diagnosis and treatment of these patients reflects the little that is known about IC physiopathology and about the genetic background of the disease. The identification of new markers may provide a better understanding and management of the syndrome. As an attempt to identify genetic markers that may be associated with IC, we evaluated the presence of some genetic polymorphisms, single nucleotide polymorphisms (SNPs), in the DNA of patients with the diagnostic criteria of IC, and we compared their prevalence among IC patients and with a control group representative of the general population. The correlation of these polymorphisms considering IC and pain intensity in these patients has not been studied in the literature. OBJECTIVES: To assess the presence of polymorphisms (SNPs) in blood samples from IC patients and to correlate the presence of polymorphisms with chronic pain. METHODS: Thirty-four female patients with a diagnosis of IC according to the NIDDK criteria and 23 control subjects (healthy women with stress urinary incontinence) were selected. Patients with the diagnosis of IC were stratified into two groups according to the degree of symptoms of chronic pain. We selected 20 polymorphisms for analysis: rs1800871, rs1800876, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, rs6746030. Genotyping was performed using the real-time PCR technique (q-PCR) and correlated with the diagnosis of IC and intensity of pain symptoms. RESULTS: The polymorphic allele (T) of the SNP rs11127292 occurred with more frequency in patients with IC compared to the control group (p= 0.01). The polymorphic allele (T) of SNP rs6311 occurred with more frequency in patients with severe pain (p= 0.03). The frequency of wild-type (A) SNP rs1799971 was higher in patients with mild to moderate pain (p= 0.04). CONCLUSION: The results indicated differences in polymorphism frequency in the patients studied, suggesting the existence of a relevant role of SNPs associated with both IC and intensity of chronic pain symptoms in these patients