Department of Anesthesiology and Intensive Care Medicine, Pain Clinic, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Laboratory for Molecular Neuroscience, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
Clin Epigenetics. 2019 Aug 28;11(1):126. doi: 10.1186/s13148-019-0731-0.
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.
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.
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.
多躯体形式障碍（MSD）的构建是不同躯体和身心医学专业患者的共同参考点，因此可用于研究躯体形式障碍原型的大型特征明确队列，以及作为功能性躯体综合征（FSS）平行研究。该疾病的特征是出现令人痛苦且功能丧失的躯体症状，慢性疼痛是最常见和最具临床相关性的主诉。疼痛是由伤害性神经纤维感知的，并通过不同的受体分子产生动作电位传递，这些受体分子在生理病理过程中决定疼痛的敏感性。先前的研究表明，对于瞬时受体电位锚蛋白 1（TRPA1），启动子区域特定 CpG 二核苷酸的受体甲基化与热痛和压痛阈值呈负相关。在这项研究中，我们假设 TRPA1 启动子甲基化调节多躯体形式障碍（MSD）患者的疼痛敏感性。我们评估了 151 名 MSD 患者和 149 名匹配的健康志愿者，使用定量感觉测试、临床和心理计量评估以及使用全血分离的 DNA 进行甲基化分析。
我们发现 CpG-628 与机械痛阈相关，CpG-411 与女性志愿者的机械痛阈相关，即甲基化水平越高，痛阈越高。一个新的发现是，在没有和严重儿童创伤的患者之间，甲基化水平有显著差异。CpG 甲基化也与疼痛的心理计量评估以及视觉模拟评分的疼痛程度相关。
我们的研究结果支持 TRPA1 的表观遗传调控在健康志愿者的机械性疼痛敏感性中起作用的假设。它们进一步提供了证据，表明儿童创伤经历可能对 MSD 患者 TRPA1 的表观遗传调控产生影响。
