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）：泌尿科慢性盆腔疼痛综合征（UCPPS）的病因学和自然史尚不清楚。爱荷华大学将与其他 MAPP 研究网络站点一起对 UCPPS 症状模式进行纵向表型研究。在这项 Trans-MAPP 研究中，我们将描述神经炎症和下丘脑垂体轴 (HPA) 失调在 UCPPS 症状和症状变化中的作用。这项工作的中心假设是 Toll 样受体 (TLR)-4 激活和 (HPA) 失调是 UCPPS 的关键潜在特征，并将与 UCPPS 症状变化、发作和疾病进展相关。为了检验这一假设，患有 UCPPS 的男性和女性将参加为期 36 个月的症状模式研究，其中将描述症状、症状变化以及发作频率和严重程度（目标 1）。每 3 个月收集一次现场调查问卷和网络调查问卷。补充 Trans-MAPP 研究将确定炎症生物标志物的作用，以及泌尿系统和非泌尿系统纵向症状模式和耀斑的应激途径（目标 2）；开发、测试和使用移动应用程序来提供疼痛和相关症状的实时生态瞬时评估（目标 3）；进行脑磁共振成像，以确定急性压力诱发的疼痛是否调节大脑网络，以及功能连接的变化是否可以预测长期疼痛症状的变化（目标 4）；并使用临床前 UCPPS 小鼠模型来确定 TLR-2/TLR-4 致敏是否与疼痛和排尿功能障碍存在机制相关（目标 5）。拟议的工作将对患有 UCPPS 的男性和女性的疾病生物标志物、遗传预测因子、实时症状测量和大脑结构/功能及其与 UCPPS 症状随时间变化的关系进行综合评估。在动物模型中，我们将探索基于 TLR-4 调节的潜在转化治疗方法。这些 Trans-MAPP 研究结果不仅将识别与症状改善、恶化和发作相关的神经炎症表型，还将揭示最终实施靶向 UCPPS 治疗的机制。