BACKGROUND Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract associated with abdominal pain and diarrhea. Pain caused by Crohn's disease likely involves neurogenic inflammation which seems to involve the ion channel transient receptor potential ankyrin 1 (TRPA1). Since the promoter methylation of TRPA1 was shown to influence pain sensitivity, we asked if the expression of TRPA1 is dysregulated in patients suffering from Crohn's disease. The methylation rates of CpG dinucleotides in the TRPA1 promoter region were determined from DNA derived from whole blood samples of Crohn patients and healthy participants. Quantitative sensory testing was used to examine pain sensitivities. RESULTS Pressure pain thresholds were lower in Crohn patients as compared to healthy participants, and they were also lower in females than in males. They correlated inversely with the methylation rate at the CpG - 628 site of the TRPA1 promoter. This effect was more pronounced in female compared to male Crohn patients. Similar results were found for mechanical pain thresholds. Furthermore, age-dependent effects were detected. Whereas the CpG - 628 methylation rate declined with age in healthy participants, the methylation rate in Crohn patients increased. Pressure pain thresholds increased with age in both cohorts. CONCLUSIONS The TRPA1 promoter methylation appears to be dysregulated in patients suffering from Crohn's disease, and this effect is most obvious when taking gender and age into account. As TRPA1 is regarded to be involved in pain caused by neurogenic inflammation, its aberrant expression may contribute to typical symptoms of Crohn's disease.

中文翻译：

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克罗恩病中瞬时受体电位锚蛋白 1 启动子甲基化和外周疼痛敏感性。

背景克罗恩病是与腹痛和腹泻相关的胃肠道的慢性炎性疾病。克罗恩病引起的疼痛可能涉及神经源性炎症，这似乎涉及离子通道瞬时受体电位锚蛋白 1 (TRPA1)。由于 TRPA1 的启动子甲基化被证明会影响疼痛敏感性，我们询问了 TRPA1 的表达是否在克罗恩病患者中失调。TRPA1 启动子区域中 CpG 二核苷酸的甲基化率由来自克罗恩患者和健康参与者全血样本的 DNA 确定。定量感官测试用于检查疼痛敏感性。结果 与健康参与者相比，克罗恩患者的压力痛阈值较低，而且女性的比例也低于男性。它们与 TRPA1 启动子的 CpG-628 位点的甲基化率呈负相关。与男性克罗恩患者相比，这种效果在女性中更为明显。机械痛阈也有类似的结果。此外，检测到年龄依赖性影响。虽然健康参与者的 CpG - 628 甲基化率随着年龄的增长而下降，但克罗恩患者的甲基化率却增加了。在两个队列中，压力痛阈值都随着年龄的增长而增加。结论 克罗恩病患者的 TRPA1 启动子甲基化似乎失调，这种影响在考虑性别和年龄时最为明显。由于 TRPA1 被认为与神经源性炎症引起的疼痛有关，