Epigenetic, chromatin-associated, and epitranscriptomic regulation in chronic pain: mechanisms and translational prospects.

Locus-, cell-, and stage-specific epigenetic reprogramming, not uniform changes, most consistently underpins mechanisms of chronic pain across models.

• Why it matters: Understanding the precise regulatory changes in gene expression is crucial for developing targeted therapies for chronic pain, yet current approaches lack validation and translational success.
• What they did: The review evaluates three regulatory layers—epigenetic mechanisms, non-coding RNAs, and epitranscriptomic modifications—highlighting evidence from pain models and human studies, and emphasizes the need for cell-resolved, longitudinal multi-omics and causal epigenome editing.
• The result: Advancing chronic pain treatment will require validated biomarkers, human tissue studies, and interventions focused on causality, moving beyond broad tissue associations and animal-only findings.