Epigenetic Mechanisms of Neural Plasticity in Chronic Neuropathic Pain

Neuropathic pain is a challenging clinical problem and remains difficult to treat. Altered gene expression in peripheral sensory nerves and neurons due to nerve injury is well documented and contributes critically to the synaptic plasticity in the spinal cord and the initiation and maintenance of chronic pain. However, our understanding of the epigenetic mechanisms regulating the transcription of pro-nociceptive (e.g., NMDA receptors and alpha 2 delta-1) and antinociceptive (e.g., potassium channels and opioid and cannabinoid receptors) genes are still limited. In this review, we summarize recent studies determining the roles of histone modifications (including methylation, acetylation, and ubiquitination), DNA methylation, and noncoding RNAs in neuropathic pain development. We review the epigenetic writer, reader, and eraser proteins that participate in the transcriptional control of the expression of key ion channels and neurotransmitter receptors in the dorsal root ganglion after traumatic nerve injury, which is commonly used as a preclinical model of neuropathic pain. A better understanding of epigenetic reprogramming involved in the transition from acute to chronic pain could lead to the development of new treatments for neuropathic pain.

Automated summary

This review summarizes recent studies on the epigenetic mechanisms involved in neuropathic pain development, focusing on the role of histone modifications, DNA methylation, and noncoding RNAs. It also discusses the proteins involved in the transcriptional control of key ion channels and neurotransmitter receptors in dorsal root ganglion.