Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
Childhood traumatization is associated with differences in TRPA1 promoter methylation in female patients with multisomatoform disorder with pain as the leading bodily symptom
复制标题
DOI：
10.1186/s13148-019-0731-0
复制
发表时间：
2019-08-28
影响因子：
5.7
通讯作者：
Karst, Matthias
中科院分区：
文献类型：
--
作者：
Achenbach, Johannes;Rhein, Mathias;Karst, Matthias
背景多躯体形式障碍（MSD）的概念是不同躯体和心身专科患者的共同参考点，因此可用于研究躯体形式障碍原型的大量特征明确的队列，并作为功能性躯体综合征（FSS）平行研究。这种疾病的特征是令人痛苦和功能丧失的躯体症状，慢性疼痛是最常见和临床相关的主诉。疼痛由伤害性神经纤维感知，并通过不同受体分子产生的动作电位转移，已知这些受体分子在病理生理过程中决定疼痛敏感性。先前的研究表明，对于瞬时受体电位锚蛋白1（TRPA 1），启动子区域中特定CpG二核苷酸的受体甲基化与热痛和压力痛阈值呈负相关。在这项研究中，我们假设TRPA 1启动子甲基化调节多瘤型疾病（MSD）患者的疼痛敏感性。对151名MSD患者和149名匹配的健康志愿者进行了定量感觉测试、临床和心理测量评估，并使用从全血中分离的DNA进行甲基化分析。结果我们发现，在女性志愿者中，CpG-628与机械痛阈相关，CpG-411与机械痛阈相关，即，较高的甲基化水平导致较高的疼痛阈值。一个新的发现是，甲基化水平在没有和严重儿童创伤的患者之间存在显着差异。CpG甲基化也与心理评估疼痛和疼痛水平的视觉模拟scale.ConclusionOur研究结果支持的假设，TRPA 1的表观遗传调控在健康志愿者的机械疼痛敏感性中发挥作用。他们进一步提供了童年创伤经历对MSD患者TRPA 1表观遗传调控的可能影响的证据。
BackgroundThe construct of multisomatoform disorder (MSD) is a common point of reference for patients in different somatic and psychosomatic specialties and therefore useful in studying large well-characterized cohorts of a prototype of a somatoform disorder and in parallel as a functional somatic syndrome (FSS). This disorder is characterized by distressing and functionally disabling somatic symptoms with chronic pain as the most frequent and clinically relevant complaint. Pain is perceived by nociceptive nerve fibers and transferred through the generation of action potentials by different receptor molecules known to determine pain sensitivity in pathophysiological processes. Previous studies have shown that for the transient receptor potential ankyrin 1 (TRPA1), receptor methylation of a particular CpG dinucleotide in the promoter region is inversely associated with both heat pain and pressure pain thresholds. In this study, we hypothesized that TRPA1 promoter methylation regulates pain sensitivity of patients with multisomatoform disorder (MSD). A cohort of 151 patients with MSD and 149 matched healthy volunteers were evaluated using quantitative sensory testing, clinical and psychometric assessment, and methylation analysis using DNA isolated from whole blood.ResultsWe found CpG -628 to be correlated with mechanical pain threshold and CpG -411 to be correlated with mechanical pain threshold in female volunteers, i.e., higher methylation levels lead to higher pain thresholds. A novel finding is that methylation levels were significantly different between patients with no and severe levels of childhood trauma. CpG methylation also correlated with psychometric assessment of pain and pain levels rated on a visual analog scale.ConclusionOur findings support the hypothesis that epigenetic regulation of TRPA1 plays a role in mechanical pain sensitivities in healthy volunteers. They further provide evidence for the possible influence of childhood traumatic experiences on the epigenetic regulation of TRPA1 in patients with MSD.