Epigenetics in anesthesiology: an overview and clinical relevance

Epigenetics, the study of heritable changes in gene expression that occur without altering the underlying DNA sequence, has emerged as an important conceptual framework for anesthesiology. The epigenome is organized into three mechanistic tiers: cytosine methylation in DNA, chemical modification of histone proteins, and gene regulation by non-coding RNA molecules. Unlike a relatively stable genome, epigenetic patterns vary between cell types, change throughout the lifespan, and are modifiable by environmental exposures, including surgical stress and anesthetic drugs. These properties make epigenetic mechanisms particularly relevant to several problems encountered in anesthetic practice. For example, interindividual variability in responses to analgesics and anesthetics, pathophysiology of chronic pain and opioid tolerance, immune dysregulation in critical illness, and long-term cognitive consequences of perioperative exposure in vulnerable populations. This review aimed to explore the fundamental concepts of epigenetics for anesthesiologists; established roles in disease conditions relevant to anesthesiology, including pain, neurodegeneration, and inflammation; and the key considerations for designing and interpreting epigenetic research in the perioperative context. Understanding the epigenome offers both a new lens through which to view the clinical phenomena encountered daily in anesthetic practice, and a potential avenue toward more individualized, mechanism-informed patient care.