Mechanistic-Based Treatment of Interstitial Cystitis/Bladder Pain Syndrome

摘要： 间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种以疼痛为特征的使人衰弱的慢性疾病， 压力和骨盆区域的不适以及泌尿系统症状。IC/BPS所涉及的疼痛可以 使人衰弱而且无法治愈。就目前情况而言，许多可用的IC/BPS治疗方法缺乏强有力的证据 对于他们的使用和昂贵的病人。此外，患者报告对医疗护理非常不满意， 将治疗描述为“试错法”，昂贵，并且有“零散的”治疗计划要遵循。 IC/BPS的治疗进展由于缺乏对病情的明确理解而停滞不前，因为症状 而且呈现方式千差万别。出于这些原因，国家组织优先考虑了改善 治疗选择和对IC/BPS的理解。领先的多机构研究网络现在已经 发现IC/BPS个体具有不同的亚组或“表型”，主要特征是 疼痛在全身的分布。IC/BPS的这些表现具有不同的临床和 神经生物学特征具体来说，虽然一部分IC/BPS患者的症状主要是 骨盆区域（“外周”表型），其他人经历骨盆外的额外疼痛， 不清醒的睡眠、认知功能障碍、情绪困扰和能量消耗（“集中”表型）。 在神经生物学特征方面，具有“集中”呈现的个体也表现出夸大的 对离体刺激的炎症反应和对诱发疼痛的增强反应。支持我们的 初步证据表明，该项目的总体目标是评估IC/BPS表型如何影响反应 两种不同的疗法，往往给予不考虑病人的表型，骨盆底物理治疗（PT）和 认知行为疗法（CBT）治疗IC/BPS。我们假设我们可以预测那些 基于报告的身体疼痛分布（主要是骨盆疼痛， 骨盆外）。我们建议进行一项随机机制试验，以评估哪些参与者可能 从每种治疗中受益（目标1），并评估神经生物学机制是否可以缓解 结果和治疗的变化（目标2）。根据个体报告的基线广泛疼痛水平， 我们将随机选择220名参与者接受8周的CBT或10周的PT。参与者将 在整个过程中接受三次评估[之前，之后和六个月]。评估包括患者报告的 结果、炎症的生物标志物和心理物理测试[在每个时间点进行]。这 该项目具有很大的潜力，以定制治疗和改善未来的IC/BPS精确医学护理工作。

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic condition characterized by pain, pressure, and discomfort in the pelvic region coupled with urinary symptoms. The pain involved in IC/BPS can be debilitating and is incurable. As it stands, many of the available treatments for IC/BPS lack strong evidence for their use and are costly to patients. Further, patients report significant dissatisfaction with medical care, describing treatments as “trial-and-error," expensive, and having “fragmented” treatment plans to follow. Treatment advances in IC/BPS have stalled due to a lack of clear understanding of the condition, as symptoms and presentations vary widely. For these reasons, national organizations have prioritized the need to improve both treatment options and understanding of IC/BPS. Leading multi-institutional research networks have now identified that individuals with IC/BPS have distinct subgroups, or “phenotypes,” largely characterized by the distribution of pain throughout the body. These presentations of IC/BPS have distinct clinical and neurobiological features. Specifically, while a proportion of individuals with IC/BPS have symptoms primarily in the pelvic region (“peripheral” phenotype), others experience additional pain outside of the pelvis coupled with unrefreshing sleep, cognitive dysfunction, emotional distress, and energy depletion (“centralized” phenotype). In terms of neurobiological features, individuals with “centralized” presentations also exhibit exaggerated inflammatory responses to ex vivo stimulation and heightened responses to evoked pain. Supported by our preliminary evidence, the overall goal of this project is to assess how IC/BPS phenotype may affect response to two different therapies often given without regard to patient phenotype, pelvic floor physical therapy (PT) and cognitive-behavioral therapy (CBT) for IC/BPS. We hypothesize that we can predict those who will respond preferentially to either form of treatment based on reported bodily pain distribution (pelvic pain primarily, pain outside of the pelvis). We are proposing a randomized mechanistic trial to evaluate which participants may benefit from each treatment (Aim 1) and evaluate whether neurobiological mechanisms may moderate outcomes and change with treatment (Aim 2). Per an individual’s reported level of baseline widespread pain, we will randomize 220 participants to receive either 8-weeks of CBT or 10-weeks of PT. Participants will receive three assessments throughout, [before, after, and at 6- months]. Assessments include patient-reported outcomes, biological markers of inflammation, and psychophysical testing [taken at each timepoint]. This project has great potential to tailor treatment and improve future IC/BPS precision-medicine care efforts.