Urology Chronic Pelvic Pain Longitudinal Symptom Patterns Study

泌尿科慢性盆腔疼痛纵向症状模式研究

• 批准号: 9120858
• 负责人: Karl J Kreder
• 金额: $ 90.81万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9120858
• 关键词: Animal Model; Biological Markers; Brain; Cellular Phone; Characteristics; Chronic Prostatitis; Clinical; Data; Disease; Disease Progression; Ecological momentary assessment; Endocrine system; Enrollment; Etiology; Flare; Frequencies; Functional disorder; Genetic Polymorphism; Goals; Health; Hormonal; Inflammation; Inflammatory; Internet; Interstitial Cystitis; Iowa; Lead; Link; Magnetic Resonance Imaging; Measurable; Measurement; Methods; Modeling; Natural History; Pain; Pathway interactions; Patients; Pattern; Pelvic Pain; Peripheral; Persons; Phenotype; Questionnaires; Receptor Activation; Research; Risk Factors; Role; Severities; Site; Stress; Structure; Symptoms; Syndrome; TLR2 gene; TLR4 gene; Technology Assessment; Testing; Therapeutic; Time; Toll-like receptors; Translational Research; Universities; Urology; Woman; Work; acute stress; associated symptom; base; brain pathway; chronic pelvic pain; clinically relevant; cohort; expectation; genetic predictors; hypothalamic pituitary axis; ineffective therapies; innovation; insight; interdisciplinary approach; men; mobile application; mobile computing; mouse model; neuroinflammation; pain symptom; pre-clinical; research study; symptomatic improvement; symptomatology; targeted treatment; urinary; urologic

DESCRIPTION (provided by applicant): The etiology and natural history of urologic chronic pelvic pain syndromes (UCPPS) are not well understood. Along with other MAPP Research Network sites, the University of Iowa will perform a longitudinal, phenotyping study of UCPPS symptom patterns. Within this Trans-MAPP study, we will characterize the role of neuroinflammation and hypothalamic pituitary axis (HPA) dysregulation in UCPPS symptoms and symptom change. The central hypothesis of this work is that toll-like receptor (TLR)-4 activation and (HPA) dysregulation are key underlying features of UCPPS and will be associated with UCPPS symptom changes, flares and disease progression. To test this hypothesis, men and women with UCPPS will be enrolled into the 36-month Symptom Patterns Study, in which symptoms, symptom change and flare frequency and severity will be characterized (Aim 1). In-person and internet-based questionnaires will be collected every 3 months. Complementary Trans-MAPP research will determine the role of inflammatory biomarkers, and stress pathways with respect to urological and non-urological longitudinal symptom patterns and flares (Aim 2); develop, test and use a mobile application to provide real-time, ecological momentary assessments of pain and associated symptoms (Aim 3); perform brain magnetic resonance imaging to determine whether acute stress- evoked pain modulates brain networks and if changes in functional connectivity are predictive of long-term pain symptom change (Aim 4); and use preclinical UCPPS mouse models to determine whether TLR-2/TLR-4 sensitization is mechanistically linked to pain and voiding dysfunction (Aim 5). The work proposed will provide an integrated assessment of disease biomarkers, genetic predictors, real-time symptom measurement and brain structure/function in men and women with UCPPS and their associations with UCPPS symptom changes over time. In the animal model we will explore potential translational therapeutic approaches based on TLR-4 modulation. These Trans-MAPP study results will not only identify neuroinflammatory phenotypes related to symptom improvement, worsening, and flares but will also reveal mechanisms by which targeted UCPPS therapy may eventually be implemented.

描述（由申请人提供）：泌尿外科慢性骨盆疼痛综合征（UCPP）的病因和自然史尚不清楚。与其他MAPP研究网站一起，爱荷华大学将对UCPPS症状模式进行纵向的表型研究。在这项反式MAPP研究中，我们将表征UCPPS症状和症状改变中神经炎症和下丘脑垂体（HPA）失调的作用。这项工作的中心假设是，Toll样受体（TLR）-4激活和（HPA）失调是UCPPS的关键基础特征，并且将与UCPPS症状的变化，耀斑和疾病进展有关。为了检验这一假设，患有UCPP的男女将被纳入36个月的症状模式研究，其中症状，症状变化，胸腔频率和严重程度将被表征（AIM 1）。面对面和基于互联网的问卷将每3个月收集一次。互补的反式MAPP研究将确定炎症生物标志物的作用，以及应力途径在泌尿外科和非神经纵向症状模式和耀斑方面（AIM 2）；开发，测试和使用移动应用程序，以提供对疼痛和相关症状的实时生态瞬时评估（AIM 3）；执行大脑磁共振成像，以确定急性应激引起的疼痛是否调节大脑网络以及功能连通性的变化是否可以预测长期疼痛症状的变化（AIM 4）；并使用临床前UCPP小鼠模型来确定TLR-2/TLR-4敏化是否与疼痛和空隙功能障碍有关（AIM 5）。提出的工作将提供对疾病生物标志物，遗传预测因素，实时症状测量和大脑结构/功能的综合评估，其中UCPPS及其与UCPPS症状的关联随时间变化。在动物模型中，我们将基于TLR-4调制探索潜在的翻译治疗方法。这些反式MAPP研究结果不仅将确定与症状改善，恶化和耀斑有关的神经炎症表型，而且还将揭示最终可以实施靶向UCPPS治疗的机制。