Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.
Department of Medicine, Surgery, and Health Sciences, University of Trieste, 34127 Trieste, Italy.
Genes (Basel). 2023 Feb 4;14(2):411. doi: 10.3390/genes14020411.
Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric age. Despite its great impact, its molecular mechanisms have still not been completely unraveled. Focusing on the impact of epigenetics in the pain complex trait, we assessed the association between chronic pain and the methylation pattern of TRPA1, a key gene related to pain sensitivity.
We conducted a systematic review retrieving articles from three different databases. After deduplication, 431 items were subjected to manual screening, and then 61 articles were selected and screened again. Of these, only six were maintained for meta-analysis and analyzed using specific R packages.
Six articles were divided into two groups (group 1: comparison of mean methylation levels between healthy subjects and patients with chronic pain; group 2: correlation between mean methylation levels and pain sensation). A non-significant mean difference was obtained from the analysis of group 1 with a value of 3.97 (95% C.I. -7.79; 15.73). Analysis of group 2 showed a high level of variability between studies (correlation = 0.35, 95% C.I. -0.12; 0.82) due to their heterogeneity (I = 97%, < 0.01).
Despite the high variability observed in the different studies analyzed, our results suggest that hypermethylation and increased pain sensitivity could be connected, possibly due to the variation of TRPA1 expression.
慢性疼痛无论在心理生理、治疗还是经济负担方面，都是一个全球性的重大健康问题，其不仅限于成年人，也涉及儿童。尽管其影响巨大，但疼痛的分子机制仍未完全阐明。本研究关注表观遗传学对疼痛复杂特征的影响，评估了慢性疼痛与 TRPA1 甲基化模式之间的关联，TRPA1 是与疼痛敏感性相关的关键基因。
我们从三个不同的数据库中进行系统检索以提取文章。去重后，有 431 项被手动筛选，然后又有 61 篇文章被再次筛选。其中，只有 6 篇被保留进行荟萃分析，并使用特定的 R 包进行分析。
6 篇文章被分为两组（组 1：健康受试者与慢性疼痛患者平均甲基化水平的比较；组 2：平均甲基化水平与疼痛感觉之间的相关性）。组 1 的分析得出平均甲基化水平的差异无统计学意义，其值为 3.97（95%置信区间 -7.79；15.73）。组 2 的分析显示由于研究之间存在高度异质性（I = 97%， < 0.01），其相关性的变异性很大（相关性 = 0.35，95%置信区间 -0.12；0.82）。
尽管分析的不同研究中观察到高度的变异性，但我们的结果表明，TRPA1 表达的变化可能导致超甲基化和疼痛敏感性增加之间存在关联。
