Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Clin Epigenetics. 2019 Nov 27;11(1):167. doi: 10.1186/s13148-019-0772-4.
Glial cells in the central nervous system play a key role in neuroinflammation and subsequent central sensitization to pain. They are therefore involved in the development of persistent pain. One of the main sites of interaction of the immune system with persistent pain has been identified as neuro-immune crosstalk at the glial-opioid interface. The present study examined a potential association between the DNA methylation of two key players of glial/opioid intersection and persistent postoperative pain.
In a cohort of 140 women who had undergone breast cancer surgery, and were assigned based on a 3-year follow-up to either a persistent or non-persistent pain phenotype, the role of epigenetic regulation of key players in the glial-opioid interface was assessed. The methylation of genes coding for the Toll-like receptor 4 (TLR4) as a major mediator of glial contributions to persistent pain or for the μ-opioid receptor (OPRM1) was analyzed and its association with the pain phenotype was compared with that conferred by global genome-wide DNA methylation assessed via quantification of the methylation in the retrotransposon LINE1.
Training of machine learning algorithms indicated that the global DNA methylation provided a similar diagnostic accuracy for persistent pain as previously established non-genetic predictors. However, the diagnosis can be based on a single DNA based marker. By contrast, the methylation of TLR4 or OPRM1 genes could not contribute further to the allocation of the patients to the pain-related phenotype groups.
While clearly supporting a predictive utility of epigenetic testing, the present analysis cannot provide support for specific epigenetic modulation of persistent postoperative pain via methylation of two key genes of the glial-opioid interface.
中枢神经系统中的神经胶质细胞在神经炎症和随后的疼痛中枢敏化中起关键作用。因此，它们参与了持续性疼痛的发展。免疫系统与持续性疼痛相互作用的主要部位之一已被确定为神经免疫交叉在神经胶质-阿片界面。本研究检查了两个胶质/阿片交叉关键参与者的 DNA 甲基化与持续性术后疼痛之间的潜在关联。
在接受乳腺癌手术的 140 名女性队列中，根据 3 年随访结果，将其分为持续性或非持续性疼痛表型，评估了胶质-阿片界面关键参与者的表观遗传调控作用。分析了编码 Toll 样受体 4（TLR4）的基因的甲基化，TLR4 是胶质细胞对持续性疼痛的主要介导物，或编码μ-阿片受体（OPRM1）的基因的甲基化，并将其与疼痛表型的相关性与通过反转录转座子 LINE1 中甲基化的定量评估的全基因组 DNA 甲基化的相关性进行了比较。
机器学习算法的训练表明，全基因组 DNA 甲基化对持续性疼痛的诊断准确性与先前建立的非遗传预测因子相似。然而，诊断可以基于单个基于 DNA 的标志物。相比之下，TLR4 或 OPRM1 基因的甲基化不能进一步有助于将患者分配到与疼痛相关的表型组。
虽然明确支持表观遗传检测的预测效用，但本分析不能通过胶质-阿片界面的两个关键基因的甲基化提供对持续性术后疼痛进行特定的表观遗传调节的支持。
