Urology Chronic Pelvic Pain Longitudinal Symptom Patterns Study

描述(申请人提供)：泌尿系慢性盆腔疼痛综合征(UCPPS)的病因和自然病史尚不清楚。爱荷华大学将与其他MAPP研究网络网站一起，对UCPPS症状模式进行纵向表型研究。在这项跨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的激活和(HPA)的失调是UCPPS的关键潜在特征，并将与UCPPS的症状变化、斑块和疾病进展相关。为了验证这一假设，患有UCPPS的男性和女性将参加为期36个月的症状模式研究，在该研究中，症状、症状变化以及闪光频率和严重程度将被表征(目标1)。面对面和基于互联网的问卷将每3个月收集一次。跨Mapp补充性研究将确定炎症生物标志物及与泌尿和非泌尿系统纵向症状模式和闪光有关的应激途径的作用(目标2)；开发、测试和利用移动应用程序对疼痛和相关症状提供实时、生态的瞬时评估(目标3)；进行脑磁共振成像，以确定急性应激诱导疼痛是否调节脑神经网络，以及功能连接性的变化是否预示长期疼痛症状的变化(目标4)；利用临床前UCPPS小鼠模型来确定TLR-2/TLR-4敏化是否与疼痛和排尿功能障碍有机械上的联系(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调节的潜在翻译治疗方法。这些跨Mapp研究结果不仅将确定与症状改善、恶化和红斑相关的神经炎性表型，还将揭示靶向UCPPS治疗最终可能实施的机制。

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.