Epigenetic Mechanisms of Neural Plasticity in Chronic Neuropathic Pain

Abstract

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 α2δ-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.

Virtual Special Issue: Epigenetics 2022

“…In this joint virtual special issue, you will see contributions spanning the neuro­epigentic landscape from some of the top authors in the field. Of particular note are several exceptional Perspective and Review papers covering epigenetic mechanisms of memory, activity-dependent brain plasticity, neuro­degeneration, and chronic pain . Beyond this, you will find new research that points to the therapeutic potential of epigenetic regulation in a number of disease contexts.…”

“…Of particular note are several exceptional Perspective and Review papers covering epigenetic mechanisms of memory, 10 activity-dependent brain plasticity, 11 neurodegeneration, 12 and chronic pain. 13 Beyond this, you will find new research that points to the therapeutic potential of epigenetic regulation in a number of disease contexts. Epigenetic modulation of the brain will be a key driver of therapeutic strategies in the future of human health.…”

HDACi: The Columbus’ Egg in Improving Cancer Treatment and Reducing Neurotoxicity?

“…Epigenetic regulation in neurons and glia cells is strictly regulated by several epigenetic modifiers and transcription factors [ 20 ]. Moreover, durable changes, both in mature and “immature” neurons, occur through post-translational alterations in histones [ 20 ].…”

“…Epigenetic regulation in neurons and glia cells is strictly regulated by several epigenetic modifiers and transcription factors [ 20 ]. Moreover, durable changes, both in mature and “immature” neurons, occur through post-translational alterations in histones [ 20 ]. In recent years, advancement in basic research on HDACs’ expression, localization ( Figure 2 ) and activity in neurons has been achieved by studies on neurodegenerative diseases.…”

What Is the Role of 2-Pore Domain Potassium Channels (K2P) in Pain?

“…1 Several voltage-gated sodium channels (Na v ), 2 voltage-gated calcium (Ca 2+ ) channels, 3 transient receptor potential (TRP) channels, 4 and other cation channels increase nociceptor responsiveness, whereas a variety of potassium (K + ) channels prevent spontaneous nociceptor activity and reduce their firing probability. 5-9 The imbalance between these 2 opposing influences, which may occur as a consequence of channel gene sequence variants, 10 effect of inflammatory mediators, 11 or transcriptional dysregulation, 12,13 promotes neuropathic pain, hyperalgesia, and allodynia. 14 Given their importance in pain modulation, voltage-gated K + channels (K v ) and 2-pore domain K + channels (K2P) are potential targets for designing novel analgesic compounds.…”