T65. GENES IN POSTMORTEM BRAIN TISSUE DIFFERENTIALLY EXPRESSED IN CHRONIC PAIN

Chronic pain affects over 1 in 5 adults in the US, and is often accompanied by psychiatric conditions such as anxiety, depression, and PTSD. Despite its prevalence and many comorbidities, the mechanisms and effects of chronic pain, especially in the brain, are unclear. Using a postmortem brain gene expression dataset (N=304) of four regions (dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), basolateral amygdala, medial amygdala), we calculated surrogate variables preserving for chronic pain in order to account for measured and unmeasured sources of heterogeneity in the data. The dataset's measured variables were checked for correlation with our surrogate variables, and the uncorrelated variables were checked for collinearity with each other. These variables were used with chronic pain in a linear regression model with gene expression (measured in log2cpm), which quantifies the association between chronic pain and gene expression, adjusted for our identified non collinear covariates and surrogate variables. We corrected for multiple testing within tissues using false-discovery rate correction. We identified three genes as significantly associated and downregulated with chronic pain in the dACC: VEGF B (vascular endothelial growth factor B) (estimate value from regression = -0.0945, SE 0.0174, FDR-adjusted P-value = 0.002), B4GALT2 (beta-1-4-galactosyltransferase 2) (estimate value = -0.0935, SE = 0.0190, P = 0.01), and LRRC59 (leucine rich repeat containing 59) (estimate value = -0.0571, SE = 0.0123, P = 0.03). These differentially expressed genes (DEGs), particularly VEGF B, suggest that chronic pain has significant impacts on gene expression in the brain – VEGF B has been previously implicated in bone cancer pain, endometriosis and endometrial cancer, rheumatoid arthritis, and other chronic pain-related conditions. The two other significant gene results have not previously been implicated in chronic pain. Future work will include differential gene expression analysis for specific cell types in the dACC, and DEGs associated with opioids commonly prescribed to treat chronic pain.