Curatolo Michele, Chiu Abby P, Chia Catherine, Ward Ava, Johnston Sandra K, Klein Rebecca M, Henze Darrell A, Zhu Wentao, Raftery Daniel
University of Washington.
Merck & Co. Inc. Rahway.
Res Sq. 2024 Jul 31:rs.3.rs-4669838. doi: 10.21203/rs.3.rs-4669838/v1.
Chronic low back pain (CLBP) and fibromyalgia (FM) are leading causes of suffering, disability, and social costs. Current pharmacological treatments do not target molecular mechanisms driving CLBP and FM, and no validated biomarkers are available, hampering the development of effective therapeutics. Omics research has the potential to substantially advance our ability to develop mechanism-specific therapeutics by identifying pathways involved in the pathophysiology of CLBP and FM, and facilitate the development of diagnostic, predictive, and prognostic biomarkers. We will conduct a blood and urine multi-omics study in comprehensively phenotyped and clinically characterized patients with CLBP and FM. Our aims are to identify molecular pathways potentially involved in the pathophysiology of CLBP and FM that would shift the focus of research to the development of target-specific therapeutics, and identify candidate diagnostic, predictive, and prognostic biomarkers.
We are conducting a prospective cohort study of adults ≥18 years of age with CLBP (n=100) and FM (n=100), and pain-free controls (n=200). Phenotyping measures include demographics, medication use, pain-related clinical characteristics, physical function, neuropathiccomponents (quantitative sensory tests and DN4 questionnaire), pain facilitation (temporal summation), and psychosocial function as moderator. Blood and urine samples are collected to analyze metabolomics, lipidomics and proteomics. We will integrate the overall omics data to identify common mechanisms and pathways, and associate multi-omics profiles to pain-related clinical characteristics, physical function, indicators of neuropathic pain, and pain facilitation, with psychosocial variables as moderators.
Our study addresses the need for a better understanding of the molecular mechanisms underlying chronic low back pain and fibromyalgia. Using a multi-omics approach, we hope to identify converging evidence for potential targets of future therapeutic developments, as well as promising candidate biomarkers for further investigation by biomarker validation studies. We believe that accurate patient phenotyping will be essential for the discovery process, as both conditions are characterized by high heterogeneity and complexity, likely rendering molecular mechanisms phenotype specific.
慢性下腰痛（CLBP）和纤维肌痛（FM）是导致痛苦、残疾和社会成本的主要原因。目前的药物治疗并未针对驱动CLBP和FM的分子机制，且尚无经过验证的生物标志物，这阻碍了有效治疗方法的开发。组学研究有潜力通过识别参与CLBP和FM病理生理学的途径，大幅提升我们开发针对特定机制的治疗方法的能力，并促进诊断、预测和预后生物标志物的开发。我们将对全面表型化和临床特征化的CLBP和FM患者进行血液和尿液多组学研究。我们的目标是识别可能参与CLBP和FM病理生理学的分子途径，从而将研究重点转向开发针对特定靶点的治疗方法，并识别候选诊断、预测和预后生物标志物。
我们正在对年龄≥18岁的CLBP患者（n = 100）、FM患者（n = 100）和无疼痛对照者（n = 200）进行前瞻性队列研究。表型测量包括人口统计学、药物使用情况、与疼痛相关的临床特征、身体功能、神经病变成分（定量感觉测试和DN4问卷）、疼痛易化（时间总和）以及作为调节因素的心理社会功能。采集血液和尿液样本以分析代谢组学、脂质组学和蛋白质组学。我们将整合整体组学数据以识别共同机制和途径，并将多组学谱与疼痛相关的临床特征、身体功能、神经性疼痛指标和疼痛易化相关联，以心理社会变量作为调节因素。
我们的研究满足了更好地理解慢性下腰痛和纤维肌痛潜在分子机制的需求。通过多组学方法，我们希望为未来治疗开发的潜在靶点识别汇聚性证据，以及为生物标志物验证研究进一步研究的有前景的候选生物标志物。我们认为准确的患者表型化对于发现过程至关重要，因为这两种病症都具有高度异质性和复杂性，可能使分子机制具有表型特异性。
