Genetically Regulated Gene Expression in the Brain Associated With Chronic Pain: Relationships With Clinical Traits and Potential for Drug Repurposing

The impact of chronic pain on brain gene expression

“…Genes differentially expressed with increasing polygenic risk of MCP included genes with previous evidence of involvement in pain and cardiac phenotypes, including Fam13b (associated with mouse cardiac phenotypes, 82), TRAF5 (vascular inflammation and atherosclerosis, 83), and FAM184B (heart disease and hip pain 64 ). These associations are in line with established links between chronic pain and heart conditions 65 , including in our own previous work showing pain gene associations with cardiac dysrhythmias in a large EHR 14 . Other MCP-PRS associated genes have previous evidence of association with pain phenotypes, including DOCK3 66 , LAMB1 67 , DUSP4 68 , and C1QTNF7 69 .…”

“…One step toward addressing this knowledge gap is through analysis at the gene expression and transcriptomic level, intermediate steps between genotype (GWAS findings) and phenotype (chronic pain). We and others have applied transcriptomic imputation approaches to translate GWAS findings into gene-tissue associations 14,15 , identifying brain regions with a putative role in chronic pain including hippocampus, cerebellum, amygdala and frontal cortex among others. However, we do not yet know which brain regions and cell types are primarily involved with chronic pain development.…”