Collier Lily, Seah Carina, Hicks Emily M, Holtzheimer Paul E, Krystal John H, Girgenti Matthew J, Huckins Laura M, Johnston Keira J A
Department of Biological Sciences, Columbia University, New York City, NY.
Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, CT.
medRxiv. 2024 May 21:2024.05.20.24307630. doi: 10.1101/2024.05.20.24307630.
Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression.
We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors. We compared findings across traits and with independent transcriptomics resources, and performed gene-set enrichment.
We identified two chronic pain DEGs: B4GALT and VEGFB in bulk dACC. We found over 2000 (primarily BLA microglia) chronic pain cell type DEGs. Findings were enriched for mouse microglia pain genes, and for hypoxia and immune response. Cross-trait DEG overlap was minimal.
Chronic pain-associated gene expression is heterogeneous across cell type, largely distinct from that in pain-related traits, and shows BLA microglia are a key cell type.
慢性疼痛影响五分之一的美国成年人，造成重大的公共卫生负担。通过研究大脑基因表达可以进一步了解慢性疼痛机制。
我们检测了慢性疼痛、偏头痛、终生使用芬太尼和羟考酮以及四个脑区（背侧前扣带回、背外侧前额叶皮质、内侧杏仁核、杏仁核基底外侧核）的慢性疼痛遗传风险中的差异表达基因（DEG），并推算来自304名死后捐赠者的细胞类型表达数据。我们比较了不同性状的研究结果，并与独立的转录组学资源进行比较，还进行了基因集富集分析。
我们在背侧前扣带回中鉴定出两个慢性疼痛DEG：B4GALT和VEGFB。我们发现了2000多个（主要是杏仁核基底外侧核小胶质细胞）慢性疼痛细胞类型DEG。研究结果在小鼠小胶质细胞疼痛基因以及缺氧和免疫反应方面得到富集。不同性状的DEG重叠极少。
慢性疼痛相关的基因表达在细胞类型上具有异质性，在很大程度上与疼痛相关性状中的表达不同，并且表明杏仁核基底外侧核小胶质细胞是关键的细胞类型。
