Prognostic biomarkers for high-impact chronic pain: Development and validation

项目总结 慢性疼痛代表着一种公共卫生危机，影响着1亿多美国人，花费超过 每年5000亿美元。慢性肌肉骨骼疼痛占所有慢性疼痛的70%-80%。一个 据估计，8%的美国成年人患有高冲击性慢性疼痛，或与严重受限的疼痛相关的疼痛 六个月或更长时间的工作、社交和自我照顾活动。慢性疼痛和高影响力的慢性疼痛 特别是-经常使用处方阿片类药物治疗，并与阿片类药物使用障碍有关。多学科 慢性疼痛治疗在人群水平上显示出不完全的恢复。然而，个体的亚群 完全反应，不改变，甚至在疼痛处理后恶化。因此，健壮且经过验证 需要诊断和预后生物标记物来识别那些高影响的慢性疼痛患者，并确定 结果的轨迹(即，恢复与持续)。因此，我们的总体目标是 发现和验证肌肉骨骼高冲击性慢性疼痛的诊断和预后生物标志物。这 Goal需要全面、多维度的评估，具有集成的数据集和复杂的 计算分析流水线，以产生可靠和有效的诊断和预后生物标记物。对这件事 最后，我们组建了一个跨学科的研究和临床团队来实施Hear倡议。这个 这项计划的目标是阐明慢性疼痛的诊断和预后生物标记物的标志 整合中枢神经系统、多组学、感觉、功能、心理社会和人口统计领域。我们将实现这一目标 目标通过两个具体目标：(1)开发肌肉骨骼高冲击性疾病的诊断和预后标记物 多学科疼痛治疗后的慢性疼痛(R61发现阶段)和(2)分析验证 在第一个AIM(R33验证阶段)开发的多模式签名。这项建议将产生有效和 临床上有用的诊断和预后生物标记物特征，以促进风险和治疗分层 患有肌肉骨骼慢性疼痛的患者。这些生物标志物对于开发更安全、更有效的药物是必不可少的 针对患者的具体治疗策略，特别是对于那些对目前的疼痛治疗难以奏效的患者 选择。我们还将确定可以改变进程的潜在可改变的生物和行为因素 消除疼痛轨迹，从而减少慢性疼痛对个人和整个社会的影响。

PROJECT SUMMARY Chronic pain represents a public health crisis that affects more than 100 million Americans and costs over $500 billion dollars annually. Chronic musculoskeletal pain conditions comprise 70-80% of all chronic pain. An estimated 8% of US adults suffer from high-impact chronic pain, or pain associated with substantially restricted work, social, and self-care activities for six or more months. Chronic pain—and high-impact chronic pain in particular—is often treated with prescription opioids and is linked to opioid-use disorder. Multidisciplinary chronic pain treatments show incomplete recovery at the population level. However, subgroups of individuals completely respond, do not change, or even worsen following pain management. Thus, robust and validated diagnostic and prognostic biomarkers are needed to identify those with high-impact chronic pain and determine the trajectory of outcome (i.e., recovery versus persistence), respectively. Therefore, our overall goal is to discover and validate diagnostic and prognostic biomarkers for musculoskeletal high-impact chronic pain. This goal will require comprehensive, multidimensional assessments with an integrated dataset and a sophisticated computational analysis pipeline to yield reliable and validated diagnostic and prognostic biomarkers. To this end, we have assembled an interdisciplinary research and clinical team to implement the HEAL initiative. The goal of this initiative is to elucidate diagnostic and prognostic biomarker signatures of chronic pain by integrating CNS, multiomic, sensory, functional, psychosocial, and demographic domains. We will achieve this goal through two specific aims: (1) develop diagnostic and prognostic markers of musculoskeletal high-impact chronic pain following multidisciplinary pain treatment (R61 Discovery Phase) and (2) analytically validate the multimodal signatures developed in the first aim (R33 Validation Phase). This proposal will yield valid and clinically useful diagnostic and prognostic biomarker signatures to facilitate risk and treatment stratification in patients with musculoskeletal chronic pain. Such biomarkers are essential to develop safer, more effective patient-specific treatment strategies, particularly for those who are refractory to current pain management options. We will also identify potentially modifiable biological and behavioral factors that can change the course of the pain trajectory and thereby reduce the impact of chronic pain on the individual and society as a whole.