The DNA damage response in neurons can lead to a proinflammatory response in microglia and other glial cells13,84. In OUD, there were a relatively large number of genes that were upregulated specifically in microglia, enriched for genes involved in neuroinflammation. Microglial activation may propagate to other neural cell types, evident by an increase in interferon responses. Indeed, we found significantly upregulated interferon response in both neuronal and glial cells of individuals with OUD. Interferon responses may modulate opioid actions in the brain and could be involved in the emergence of symptoms of opioid withdrawal110.
