Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence
Adam J. Dourson, Adam Willits, Namrata G.R. Raut, Leena Kader, Erin E. Young, Michael P. Jankowski, Vidya Chidambaran
Abstract
Background: Chronic postsurgical pain (CPSP) in children remains an important problem with no effective preventive or therapeutic strategies. Recently, genomic underpinnings explaining additional interindividual risk beyond psychological factors have been proposed. Aims: We present a comprehensive review of current preclinical and clinical evidence for genetic and epigenetic mechanisms relevant to pediatric CPSP. Methods: Narrative review. Results: ) and miRNAs (miR-96/7a) have shown translational implications. Animal studies also suggest that crosstalk between neurons and immune cells may be involved in nociceptive priming observed in neonates. In children, differential DNA methylation in regulatory genomic regions enriching GABAergic, dopaminergic, and immune pathways, as well as polygenic risk scores for enhanced prediction of CPSP, have been described. Genome-wide studies in pediatric CPSP are scarce, but pathways identified by adult gene association studies point to potential common mechanisms. Conclusions: Bench-to-bedside genomics research in pediatric CPSP is currently limited. Reverse translational approaches, use of other -omics, and inclusion of pediatric/CPSP endophenotypes in large-scale biobanks may be potential solutions. Time of developmental vulnerability and longitudinal genomic changes after surgery warrant further investigation. Emergence of promising precision pain management strategies based on gene editing and epigenetic programing emphasize need for further research in pediatric CPSP-related genomics.