Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.

ABSTRACT

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management.