The role of DNA methylation in the detrimental effects of early life adversity on the use of opioid analgesics

Exposure to toxic stress during childhood has detrimental effects on health, including pain and addiction to opioid analgesics. This PhD project will test the hypothesis that exposure to early life stress (ELS) affects DNA methylation resulting in altered gene expression leading to vulnerability to the detrimental effects of opioid analgesics. The aim of the project will be to identify mechanisms and biological markers that account for vulnerabilities to opioid addiction in those exposed to ELS. This will be achieved by exploring the effects, of toxic stress during development on human induced pluripotent stem cell derived neurones and mice. These two models will be used to establish changes in 1) human neurophysiology and 2) mouse behavioural responses to opioids as well as associated differential DNA methylation. Mechanisms linking stress to detrimental effects of opioids will be established using gene editing in both models.