Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure
Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure
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DOI：
10.1016/j.pain.2013.04.037
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发表时间：
2013-08-01
期刊：
影响因子：
7.4
通讯作者：
McLean, Samuel A.
中科院分区：
文献类型：
--
作者：
Bortsov, Andrey V.;Smith, Jennifer E.;McLean, Samuel A.
影响下丘脑-垂体-肾上腺轴功能的个体脆弱性因素可能导致创伤应激暴露后出现持续性肌肉骨骼疼痛的风险。这项研究的目的是评估编码FK506结合蛋白51和FKBP5的基因多态性与两次常见创伤暴露后6周肌肉骨骼疼痛严重程度的相关性。这项研究包括来自两个以急诊科为基础的前瞻性队列的数据：一个发现队列(n=949)经历机动车碰撞的欧洲美国人，以及一个复制队列(n=53)经历性侵的成年欧洲美国女性。DNA是在最初评估时从创伤幸存者身上收集的。创伤暴露后6周的总体疼痛和颈部疼痛采用0-10数字评分标准进行评估。在对多重比较进行调整后，在发现的队列中，6个FKBP5基因多态与总体和颈部疼痛显著相关(最小P<；0.0001)。Rs3800373、rs9380526、rs9394314、rs2817032和rs2817040与创伤后6周颈部疼痛和/或全身疼痛的关联在性侵犯队列中重复，在每个病例中显示出相同的影响方向。这项研究的结果表明，FKBP5的基因变异会影响在汽车碰撞和性侵犯后几周内经历的肌肉骨骼疼痛症状的严重程度。这些结果表明，糖皮质激素途径影响持续性创伤后疼痛的发展，这种途径可能是旨在改善创伤后恢复的药物干预的靶点。(C)2013年国际疼痛研究协会。爱思唯尔出版公司版权所有。
Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n = 949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n = 53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0-10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P < 0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.