Table_2_Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain.pdf

Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON).
Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS.
Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin).
Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.

研究目的：尽管慢性广泛性疼痛（chronic widespread pain, CWP）患者常出现全身性肌肉疼痛、疲劳、焦虑及抑郁症状，但CWP的分子发病机制尚未完全阐明。此外，缺乏有效生物标志物常导致该病的诊断与治疗陷入困境。本研究旨在探讨CWP患者与健康对照（controls, CON）群体中，疼痛强度、心理困扰状态与血浆蛋白质之间的关联。
研究方法：本研究采用二维凝胶电泳（two-dimensional gel electrophoresis）技术，对15例CWP患者及23例健康对照的血浆蛋白质组进行分析。采用正交偏最小二乘分析（Orthogonal Partial Least Square, OPLS），分别筛选与CWP患者疼痛强度（采用数字评分量表（numeric rating scale）评估）相关的蛋白质，以及与CWP患者及健康对照群体心理困扰状态（采用医院焦虑抑郁量表（Hospital and Depression Scale, HADS）评估）相关的蛋白质。通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）及串联质谱（tandem MS）对差异显著的蛋白质进行鉴定。
研究结果：在CWP患者中，疼痛强度与主要参与代谢及免疫过程的血浆蛋白显著相关（例如激肽原-1、纤维蛋白原γ链及铜蓝蛋白）；而心理困扰状态则与参与免疫应答、铁离子代谢及脂质代谢的血浆蛋白相关（例如补体因子B、补体C1r亚基、血液结合素及簇集蛋白）。
讨论：本研究表明，CWP患者中不同的血浆蛋白质组模式分别与疼痛强度及心理困扰状态存在关联。参与凝血级联反应及免疫过程的蛋白质与各项临床结局均呈现强相关性。通过分析CWP患者的血浆蛋白质组以筛选潜在生物标志物，可为揭示CWP持续存在的全身系统性发病机制提供直观的分子层面依据。