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）发病率不详，并与抑郁症相关。骨盆疼痛的多学科评估（MAPP）在第一阶段非常成功，第二阶段承诺对UCPPS表型和潜在机制有更深入的了解。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患者报告结果的工作组。在这里，我们试图通过研究UCPPS及其潜在机制与抑郁症之间的关系，在这些重要努力的基础上，进行远远超出MAPP I的创新研究。我们的研究中心将招募参与者参加一个大型症状模式研究（每个研究中心N = 106），并纵向追踪他们的骨盆疼痛轨迹，以及识别症状发作和恶化的危险因素。作为症状模式研究的一部分，患者将通过表现症状、生物标志物和神经影像学来表征。我们的具体建议包括一些神经影像学研究，以询问脑外周连接，以及研究风险-奖励回路失调，这可能与盆腔疼痛合并症有关。为了更好地描述UCPPS症状和合并症，我们还建议开发一个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学表型研究，其中使用最先进的访谈来了解UCPPS患者的合并症诊断。最后，我们建议使用临床相关的小鼠UCPPS模型进行一系列机制研究，以确定TLR4作为驱动疼痛、排尿功能障碍和焦虑/抑郁的触发器的整合者的作用。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.