PDF(Pubmed)
Abstract：
OBJECTIVE: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns.
METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes.
RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P.
CONCLUSIONS: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.
METHODS: Cytokines, chemokines, and peptides associated with nociception and pain were measured in legacy serum samples from CP patients (N = 99) enrolled in the North American Pancreatitis Studies. The unsupervised hierarchical cluster analysis was applied to cluster CP patients based on their biomarker profile. Classification and regression tree was used to assess whether these biomarkers can predict pain outcomes.
RESULTS: The hierarchical cluster analysis revealed a subset of patients with predominantly constant, mild-moderate pain exhibited elevated interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-2 (IL-2), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP1) whereas patients with higher interleukin-4 (IL-4), interleukin-8 (IL-8) and calcitonin gene related peptide (CGRP) were more likely to have severe pain. Interestingly, analyses of each individual biomarker revealed that patients with constant pain had reduced circulating TNFα and fractalkine. Patients with severe pain exhibited a significant reduction in TNFα as well as trends towards lower levels of IL-6 and substance P.
CONCLUSIONS: The observations from this study indicate that unique pain experiences within the chronic pancreatitis population can be associated with distinct biochemical signatures. These data indicate that further hypothesis-driven analyses combining biochemical measurements and detailed pain phenotyping could be used to develop precision approaches for pain management in patients with chronic pancreatitis.
摘要：
目的：慢性胰腺炎（CP）与使人衰弱的难治性疼痛有关。CP疼痛的不同亚型以前已经根据严重程度进行了表征(没有，轻度-中度,严重)和时间(无，间歇性,恒定)疼痛的性质，但目前尚无基于机制的工具来指导疼痛管理.这项探索性研究旨在确定是否可以在患者血清中检测到潜在的疼痛生物标志物，以及它们是否与特定的疼痛模式相关。
方法：细胞因子，趋化因子,在北美胰腺炎研究中登记的CP患者(N=99)的遗留血清样品中测量与伤害感受和疼痛相关的肽。无监督层次聚类分析被应用于基于其生物标志物谱的CP患者的聚类。分类和回归树用于评估这些生物标志物是否可以预测疼痛结果。
结果：层次聚类分析揭示了一个子集的患者主要是恒定的，轻度-中度疼痛显示白细胞介素-1β（IL-1β）升高，白细胞介素-6（IL-6），白细胞介素-2（IL-2），肿瘤坏死因子α（TNFα），和单核细胞趋化蛋白-1（MCP1），而白细胞介素-4（IL-4）较高的患者，白细胞介素-8（IL-8）和降钙素基因相关肽（CGRP）更容易出现严重疼痛。有趣的是,对每个个体生物标志物的分析显示,持续疼痛的患者循环TNFα和fractalkine降低.严重疼痛患者TNFα显著降低，IL-6和P物质水平也有降低的趋势。
结论：这项研究的观察结果表明，慢性胰腺炎人群中独特的疼痛经历可能与不同的生化特征相关。这些数据表明，结合生化测量和详细疼痛表型的进一步假设驱动分析可用于开发慢性胰腺炎患者疼痛管理的精确方法。
方法：细胞因子，趋化因子,在北美胰腺炎研究中登记的CP患者(N=99)的遗留血清样品中测量与伤害感受和疼痛相关的肽。无监督层次聚类分析被应用于基于其生物标志物谱的CP患者的聚类。分类和回归树用于评估这些生物标志物是否可以预测疼痛结果。
结果：层次聚类分析揭示了一个子集的患者主要是恒定的，轻度-中度疼痛显示白细胞介素-1β（IL-1β）升高，白细胞介素-6（IL-6），白细胞介素-2（IL-2），肿瘤坏死因子α（TNFα），和单核细胞趋化蛋白-1（MCP1），而白细胞介素-4（IL-4）较高的患者，白细胞介素-8（IL-8）和降钙素基因相关肽（CGRP）更容易出现严重疼痛。有趣的是,对每个个体生物标志物的分析显示,持续疼痛的患者循环TNFα和fractalkine降低.严重疼痛患者TNFα显著降低，IL-6和P物质水平也有降低的趋势。
结论：这项研究的观察结果表明，慢性胰腺炎人群中独特的疼痛经历可能与不同的生化特征相关。这些数据表明，结合生化测量和详细疼痛表型的进一步假设驱动分析可用于开发慢性胰腺炎患者疼痛管理的精确方法。
