BACKGROUND The 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. RESULTS We 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. CONCLUSION Our 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.

中文翻译：

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儿童创伤与女性多发性畸形患者中以疼痛为主要身体症状的TRPA1启动子甲基化差异有关。

背景技术多躯体形式障碍（MSD）的构建是不同躯体和心身专科患者的共同参考点，因此可用于研究大量特征明确的躯体形式障碍原型，并同时作为功能性躯体综合症（FSS） ）。这种疾病的特征是使躯体症状困扰和功能丧失，慢性疼痛是最常见且与临床相关的主诉。疼痛由伤害性神经纤维感知，并通过已知在病理生理过程中确定疼痛敏感性的不同受体分子通过动作电位的产生而转移。先前的研究表明，对于瞬时受体电位锚蛋白1（TRPA1），启动子区域中特定CpG二核苷酸的受体甲基化与热痛阈值和压力痛阈值均呈负相关。在这项研究中，我们假设TRPA1启动子甲基化调节多体形障碍（MSD）患者的疼痛敏感性。使用定量感官测试，临床和心理测评以及使用从全血中分离出的DNA进行甲基化分析，对151名MSD患者和149名匹配的健康志愿者进行了评估。结果我们发现女性志愿者中CpG -628与机械疼痛阈值相关，而CpG -411与机械疼痛阈值相关，即较高的甲基化水平导致较高的疼痛阈值。一项新发现是，无儿童期创伤和严重儿童期创伤的患者之间的甲基化水平显着不同。CpG甲基化还与疼痛的心理测评和以视觉模拟量表评分的疼痛水平相关。结论我们的研究结果支持以下假设：TRPA1的表观遗传调控在健康志愿者中对机械性疼痛敏感性起作用。他们进一步为儿童创伤经历对MSD患者TRPA1的表观遗传调控可能产生的影响提供了证据。