Genomics plays an important role in the predisposition to higher pain sensitivity, reactivity to stress, and immune responses underlying nociceptive plasticity of biological pathways, leading to the pathologic maintenance of post-surgical pain. In addition, gene -environmental interactions in the form of epigenetic modifications (which can lead to gene expression changes) in stress-pain relevant pathways (GABA/dopaminergic, opioid, and HPA axis pathways) are associated with CPSP. Dr.Chidambaran will present genetics-based strategies for preemptive prediction of CPSP using systems biology-based polygenic risk scores and DNA methylation changes. She will discuss gene-epigenetic interaction mechanisms (methylation quantitative trait loci) underlying CPSP in children undergoing major musculoskeletal surgery. She will also present novel data about longitudinal immune cell subsets, cytokine markers and DNAm changes post-surgery. These will be discussed in light of chromatin accessibility to provide a more comprehensive picture of immunogenetic mechanisms involved in CPSP.