The Epigenetic Mechanisms Involved in Chronic Pain in Rodents: A Mini-Review

Current Neuropharmacology, 2022 · DOI: 10.2174/1570159X19666210924104757 · Published: January 1, 2022

Simple Explanation

Chronic pain is a widespread neurological problem affecting around 30% of people globally, leading to significant economic and social costs. While scientists have made strides in understanding chronic pain, effectively managing and treating it remains a challenge. Recent research indicates that epigenetic mechanisms, such as DNA/RNA methylation, histone modification, and circular RNA regulation, contribute to the development of chronic pain. Epigenetics involves heritable gene modifications without altering the DNA sequence itself. These modifications play a crucial role in regulating gene expression and are essential in the development of chronic pain. Understanding the functional involvement of epigenetic modifications in chronic pain is fundamentally important. This review focuses on epigenetic modifications like DNA/RNA methylation, histone acetylation, and circular RNA regulation in the spinal cord and dorsal root ganglion (DRG) of rodents experiencing chronic pain. The aim is to provide a brief overview of these epigenetic mechanisms and their involvement in chronic pain.

Study Duration

Not specified

Participants

Rodents

Evidence Level

Review article

Key Findings

1
DNA methylation, mediated by enzymes like DNMTs and TETs, plays a role in chronic pain development. Specifically, the upregulation of methyltransferase DNMT3a is widely involved in chronic pain induced by a variety of causes, and it promotes the occurrence and development of chronic pain by inhibiting the transcription of analgesic-related genes by increasing the methylation level of these genes.
2
RNA methylation, particularly m6A modification, affects mRNA stability and translation efficiency of pain-related genes. Until now, the overall change of m6A modification is controversial, and the mechanism of all the m6A-related enzymes involved in chronic pain needs further in-depth exploration.
3
Histone acetylation, regulated by HATs and HDACs, influences gene transcription related to chronic pain. The existing studies demonstrate inconsistent changes in total level of acetylated histones and HATs/HDACs expression in chronic pain.

Research Summary

This review summarizes current knowledge about four epigenetic modifications—DNA/RNA methylation, histone acetylation, and circRNAs—in chronic pain. Epigenetic modifications may shed lights on the chronic pain management. circRNAs, highly expressed in the nervous system and characterized by tissue specificity, non-degradability, and high conservation, may play a critical role in chronic pain. Until now, the studies on circRNAs have focused on the mixed tissue analysis in the spinal cord and DRG. More translational research on humans is needed to advance our knowledge, explore the real clinical potential, and eventually make technology and therapeutics more accessible to the labs and clinics. Epigenetic regulation is tissue and site-specific. Future research needs to address unanswered questions, such as whether epigenetic changes in the nervous system can be detected in easily accessible body fluids.

Practical Implications

Therapeutic Targets

Modulation of DNMT3a and DNMT3b may offer a promising therapeutic strategy for chronic pain management.

Drug Development

Intervention in the acetylation modification process may identify new drug targets for pain treatment.

Biomarker Identification

Identifying epigenetic modifications in accessible sites like blood or saliva could facilitate non-invasive human studies.

Study Limitations

1
Most research has been conducted on animals, and translation to clinical settings is lacking.
2
Scientific knowledge about epigenetics is far from comprehensive, and many issues remain to be investigated.
3
Studies on circRNAs have focused on mixed tissue analysis, neglecting the contribution of different cell types.

Your Feedback

Was this summary helpful?

Back to Neurology