Pelvic Pain and Depression

描述（由申请人提供）：泌尿系统慢性盆腔疼痛综合征（UCPPS）导致未知的发病率，并与抑郁症有关。骨盆疼痛的多学科评估（MAPP）在I期非常成功，II期有望更好地了解UCPPS表型和潜在机制。我们的团队为许多关键的Trans-MAPP计划做出了贡献，包括专注于动物模型，神经成像和UCPPS中患者报告结果的工作组。在这里，我们寻求建立在这些重要的努力与创新的研究，远远超出MAPP我通过检查UCPPS，其潜在的机制，和抑郁症之间的关系。我们的研究中心将招募患者参加一项大型症状模式研究（每个研究中心N = 106），并对其进行纵向随访，以跟踪盆腔疼痛的轨迹，并确定症状发作和加重的风险因素。作为症状模式研究的一部分，患者将通过表现出的症状、生物标志物和神经影像学来表征。我们的特定部位的建议包括一些神经影像学研究，询问大脑周边连接，以及研究可能与盆腔疼痛合并症相关的风险回报回路失调。为了更好地表征UCPPS症状和合并症，我们还建议开发一种基于手机的应用程序，用于高分辨率监测UCPPS症状，以及一项密集的精神病表型研究，其中使用最先进的访谈来了解UCPPS患者的合并症诊断。最后，我们提出了一系列的机制研究，使用临床相关的小鼠UCPPS模型来定义TLR 4的作用，作为触发驱动疼痛，排尿功能障碍和焦虑/抑郁症的集成。总之，这些研究将产生对UPPS表型和机制的多维理解，为个性化和有效的治疗奠定基础。

DESCRIPTION (provided by applicant): Urologic chronic pelvic pain syndromes (UCPPS) cause untold morbidity and are associated with depression. Multidisciplinary Assessment of Pelvic Pain (MAPP) has been very successful during Phase I, and Phase II promises even greater understanding of UCPPS phenotypes and the underlying mechanisms. Our team has contributed to many key Trans-MAPP initiatives, including workgroups focusing on animal models, neuroimaging, and patient-reported outcomes in UCPPS. Here, we seek to build upon these important efforts with innovative studies that go well beyond MAPP I by examining the relationship between UCPPS, its underlying mechanisms, and depression. Our site will recruit into a large Symptom Pattern Study (N = 106 per site) and follow them longitudinally to track the trajectory of pelvic pain, as well as to identify risk factors for symptom flares and exacerbations As part of the Symptom Pattern Study, patients will be characterized by presenting symptoms, biomarkers, and neuroimaging. Our site-specific proposal includes a number of neuroimaging studies to interrogate brain-periphery connections as well as to study dysregulation in risk-reward circuitry that may be relevant to pelvic pain comorbidities. To better characterize UCPPS symptoms and comorbidities, we also propose to develop a mobile-phone-based app for high- resolution monitoring of UCPPS symptoms, as well as an intense psychiatric phenotyping study in which state-of-the-art interviews are used to understand comorbid diagnoses of UCPPS patients. Finally, we propose a series of mechanistic studies using clinically relevant murine UCPPS models to define the role of TLR4 as an integrator of triggers that drive pain, voiding dysfunction, and anxiety/depression. In summary, these studies will yield a multi-dimensional understanding of UPPS phenotypes and mechanisms that set the stage for individualized and effective therapies.