Paoloni-Giacobino Ariane, Luthi François, Stenz Ludwig, Le Carré Joane, Vuistiner Philippe, Léger Bertrand
Medicine Faculty, Department of Genetic Medicine and Development, Geneva University, Geneva, Switzerland.
Institute for Research in Rehabilitation, Clinique romande de réadaptation, Sion, Switzerland.
J Pain Res. 2020 Jun 2;13:1289-1296. doi: 10.2147/JPR.S251782. eCollection 2020.
The INTERMED instrument, which was developed to measure patient's biopsychosocial (BPS) complexity, represents a powerful diagnostic and therapeutic tool. Epigenetic changes are the interface between signals from the environment and genetic modifications, affecting gene expression, in particular, by DNA methylation of CpG dinucleotides in promotor regions of the corresponding genes. The brain-derived neurotrophic factor (BDNF) gene plays a crucial role in the central sensitization (CS) of pain. In this study, we hypothesized that chronic pain modifies the methylation levels of the BDNF gene in a manner that is interconnected with the BPS status.
Fifty-eight chronic musculoskeletal pain patients (CMSP) were enrolled in the study. DNA was extracted from blood samples, the methylation levels of 13 CpG sites in the BDNF promoter were measured by pyrosequencing, and association studies with various patient parameters and the INTERMED scores were performed.
Interestingly, a negative correlation (-0.40) was found between the total INTERMED scores and the average CpG methylation values of the BDNF gene, but no correlation was observed with the severity of pain, degree of anxiety, depression, or kinesiophobia and catastrophism. Moreover, the association was independent of age, sex and level of comorbidities.
This result shows that CMSP, in association with its biopsychosocial context, epigenetically decreases the degree of methylation of the BDNF promoter and should therefore increase the level of BDNF transcription. It also suggests a role of the INTERMED tool to detect a relationship between the BPS complexity and the epigenetic control of a target gene. The possible upregulation of BDNF expression might be, at least in part, the signal for chronic pain-induced central sensitization (CS). This could partly explain why patients with a higher level of complexity feel more pain than those with lower complexity.
用于测量患者生物心理社会（BPS）复杂性的INTERMED工具是一种强大的诊断和治疗工具。表观遗传变化是环境信号与基因修饰之间的界面，尤其通过相应基因启动子区域中CpG二核苷酸的DNA甲基化来影响基因表达。脑源性神经营养因子（BDNF）基因在疼痛的中枢敏化（CS）中起关键作用。在本研究中，我们假设慢性疼痛以与BPS状态相互关联的方式改变BDNF基因的甲基化水平。
58名慢性肌肉骨骼疼痛患者（CMSP）纳入本研究。从血样中提取DNA，通过焦磷酸测序测量BDNF启动子中13个CpG位点的甲基化水平，并进行与各种患者参数和INTERMED评分的关联研究。
有趣的是，发现INTERMED总分与BDNF基因的平均CpG甲基化值之间存在负相关（-0.40），但未观察到与疼痛严重程度、焦虑程度、抑郁程度或运动恐惧和灾难化之间存在相关性。此外，这种关联独立于年龄、性别和合并症水平。
该结果表明，CMSP与其生物心理社会背景相关联，在表观遗传上降低了BDNF启动子的甲基化程度，因此应增加BDNF转录水平。这也表明INTERMED工具在检测BPS复杂性与靶基因表观遗传控制之间关系方面的作用。BDNF表达的可能上调可能至少部分是慢性疼痛诱导的中枢敏化（CS）的信号。这可以部分解释为什么复杂性较高的患者比复杂性较低的患者感觉更疼痛。
