Strath Larissa J, Meng Lingsong, Zhang Yutao, Rani Asha, Huo Zhiguang, Foster Thomas C, Fillingim Roger B, Cruz-Almeida Yenisel
Pain Research and Intervention Center of Excellence (PRICE) at the University of Florida, Gainesville, FL, USA.
Department of Health Outcomes and Biomedical Informatics, the University of Florida, Gainesville, FL, USA.
J Alzheimers Dis Rep. 2024 Nov 24;8(1):1549-1557. doi: 10.1177/25424823241289376. eCollection 2024.
Chronic pain and Alzheimer's disease (AD) are prevalent in older age and their etiologies remain to be understoodand evidence supports potential associations between the two. Both high impact pain and AD have been previously associated with differences in the epigenome. Interactions with the epigenome may serve as a possible underlying mechanism linking high impact pain and AD.
To complete epigenetic canonical pathways analyses related to AD in individuals with and without high-impact knee pain.
This manuscript aimed to explore differences in DNA methylation patterns in genes and pathways associated with AD. Blood samples of cognitively intact, community-dwelling adults with high impact knee painmversus pain-free controls were compared on their DNA methylation levels of AD-related genes. Pathway enrichment analysis was performed on significantly different DNA Methylation probes by pain group.
There were significant DNA methylation differences between the high impact versus the pain-free control groups in genes and pathways associated with AD (p < 0.05). We found a total of 17,563 differentially methylated CpG probes, including 13,411 hypermethylated CpG probes and 4152 hypomethylated CpG probes. Further, pathway analysis revealed these differences were significantly associated with AD-related pathways associated with AD progression.
This study sample showed AD-related DNA methylation differences and associated potential canonical pathways in those with and without high impact knee pain. These results highlight the need to study overlapping epigenetic modifications underlying high impact pain and AD pathologies. Further studies, including gene expression, are needed to further explore the relationship between epigenetics, chronic pain, and AD.
慢性疼痛和阿尔茨海默病（AD）在老年人中普遍存在，其病因尚待明确，且有证据支持两者之间存在潜在关联。此前，高强度疼痛和AD均与表观基因组差异有关。与表观基因组的相互作用可能是连接高强度疼痛和AD的潜在机制。
对有和没有高强度膝关节疼痛的个体完成与AD相关的表观遗传经典通路分析。
本研究旨在探索与AD相关的基因和通路中DNA甲基化模式的差异。比较认知功能正常、居住在社区的有高强度膝关节疼痛的成年人与无疼痛对照组的血液样本中AD相关基因的DNA甲基化水平。按疼痛组对显著不同的DNA甲基化探针进行通路富集分析。
在与AD相关的基因和通路中，高强度疼痛组与无疼痛对照组之间存在显著的DNA甲基化差异（p < 0.05）。我们共发现17,563个差异甲基化的CpG探针，其中包括13,411个高甲基化的CpG探针和4,152个低甲基化的CpG探针。此外，通路分析显示这些差异与AD进展相关的AD相关通路显著相关。
本研究样本显示，有和没有高强度膝关节疼痛的个体存在与AD相关的DNA甲基化差异及相关潜在经典通路。这些结果凸显了研究高强度疼痛和AD病理背后重叠的表观遗传修饰的必要性。需要进一步开展包括基因表达研究在内的研究，以进一步探索表观遗传学、慢性疼痛和AD之间的关系。
