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Review Open Access

Epigenetics of pain highways (Review)

  • Authors:
    • Kawalpreet K. Aneja
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    Affiliations: Department of Health Sciences, University of the People, Pasadena, CA 91101, USA
    Copyright: © Aneja et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 7
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    Published online on: November 25, 2025
       https://doi.org/10.3892/ije.2025.30
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Abstract

According to the International Association for the Study of Pain, ‘Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’. Chronic pain may be the result of tissue injury, nerve damage, surgical procedures, chemotherapy and chronic diseases, such as diabetes. In addition to physical causes, emotional and environmental stressors, exacerbated by factors such as climate change, are increasingly recognized as contributors to chronic pain and its associated sensitization patterns. One of the most underexplored areas in pain research is the epigenetic regulation of ion channels that modulate nociceptive pathways. Emerging evidence highlights epigenetic mechanisms, such as histone modifications, DNA methylation, microRNA (miRNA/miR) regulation and the activity of the RE1‑silencing transcription factor (REST) complex, as key modulators of ion channel conductance in nociceptors. For example, REST downregulates Nav1.8 sodium channels and Kv and K2P potassium channels and the µ‑opioid or MOP receptor (Oprm1 gene) in dorsal root ganglion (DRG) neurons, contributing to neuropathic pain. Similarly, miRNAs, such as miR‑183 directly target TRPV1 and multiple sodium channel isoforms (Nav1.3, Nav1.7 and Nav1.8) in DRG neurons and reduce osteoarthritic pain. Central nervous system‑specific miRNAs, such as miR‑124 and miR‑219 modulate the calmodulin‑dependent protein kinase and methyl‑CpG binding protein 2 pathways, reducing nociceptive signaling and offering promising avenues for future pain therapies. The present review summarizes the current knowledge of these epigenetic modulators of ion channels and discusses how these findings may complement traditional pharmacological approaches to develop more effective strategies for chronic pain management. 
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Aneja KK: Epigenetics of pain highways (Review). Int J Epigen 5: 7, 2025.
APA
Aneja, K.K. (2025). Epigenetics of pain highways (Review). International Journal of Epigenetics, 5, 7. https://doi.org/10.3892/ije.2025.30
MLA
Aneja, K. K."Epigenetics of pain highways (Review)". International Journal of Epigenetics 5.1 (2025): 7.
Chicago
Aneja, K. K."Epigenetics of pain highways (Review)". International Journal of Epigenetics 5, no. 1 (2025): 7. https://doi.org/10.3892/ije.2025.30
Copy and paste a formatted citation
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Spandidos Publications style
Aneja KK: Epigenetics of pain highways (Review). Int J Epigen 5: 7, 2025.
APA
Aneja, K.K. (2025). Epigenetics of pain highways (Review). International Journal of Epigenetics, 5, 7. https://doi.org/10.3892/ije.2025.30
MLA
Aneja, K. K."Epigenetics of pain highways (Review)". International Journal of Epigenetics 5.1 (2025): 7.
Chicago
Aneja, K. K."Epigenetics of pain highways (Review)". International Journal of Epigenetics 5, no. 1 (2025): 7. https://doi.org/10.3892/ije.2025.30
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