Pelvic Pain and Depression

描述(申请人提供)：泌尿系慢性盆腔疼痛综合征(UCPPS)会导致不计其数的发病率，并与抑郁症相关。骨盆疼痛多学科评估(MAPP)在第一阶段非常成功，第二阶段有望更好地了解UCPPS的表型和潜在机制。我们的团队为许多关键的跨Mapp倡议做出了贡献，包括工作组专注于UCPPS中的动物模型、神经成像和患者报告的结果。在这里，我们试图以这些重要的努力为基础，通过研究UCPPS及其潜在机制和抑郁症之间的关系，进行远远超出MAPP I的创新研究。我们的网站将招募参加大型症状模式研究(每个站点N=106)，并纵向跟踪他们，以跟踪骨盆疼痛的轨迹，以及确定症状爆发和恶化的风险因素。作为症状模式研究的一部分，患者将以症状、生物标记物和神经成像为特征。我们的特定部位建议包括一些神经成像研究，以询问大脑-外周连接，以及研究风险-回报回路中的失调，这可能与骨盆疼痛合并症有关。为了更好地描述UCPPS的症状和合并症，我们还建议开发一款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患者的共病诊断。最后，我们提出了一系列使用临床相关的小鼠UCPPS模型的机制研究，以确定TLR4作为驱动疼痛、排尿功能障碍和焦虑/抑郁的触发因素的整合因子的作用。总之，这些研究将产生对UPPS表型和机制的多维理解，这些表型和机制为个性化和有效的治疗奠定了基础。

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.