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

Abstract

: Chronic pain, as a common distressing neurological disorder, about 30% of the global population suffers from it. In addition to being highly prevalent, chronic pain causes heavy economic and social burden. Although substantial progress has been achieved to dissect the underlying mechanism of chronic pain in the past few decades, the incidence and treatment of this neurological illness is yet not properly managed in clinical practice. While nerve injury-, chemotherapy- or inflammation-induced functional regulation of gene expression in the dorsal root ganglion and spinal cord are extensively reported to be involved in the pathogenic process of chronic pain, the specific mechanism of these altered transcriptional profile still remains unclear. Recent studies have shown that epigenetic mechanisms, including DNA/RNA methylation, histone modification and circular RNAs regulation, are involved in the occurrence and development of chronic pain. In this review, we provide a description of research on the role of epigenetic mechanism in chronic pain, summarize the latest clinical and preclinical advance in this field, and propose the potential directions for further research to elucidate the molecular mechanism underlying the pathogenesis of chronic pain.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study

“…They play a role in modulating brain development, neuronal differentiation, and synaptic plasticity and act as important regulatory factors in the occurrence and development of neurological diseases such as Parkinson's disease and Alzheimer's disease [45][46][47]. Some studies hold that circRNAs may be involved in regulating chronic pain, including the development of pain and central sensitization [25,48]. Chen et al [49] proved that spinal cord circKcnk9 mediated IBS-associated chronic visceral hyperalgesia.…”

“…They are highly conservative, extensively distributed, and tissue-specific and act as the key competing endogenous RNA (ceRNA) of epigenetic regulatory factors [22,23]. Recent studies have found that circRNAs play an important role in chronic pains, including lumbago and neuropathic pain in degenerative diseases [24][25][26][27]. As the "molecular sponge" of miRNAs, circRNAs can competitively bind with miRNAs to regulate the mRNA transcription of target genes; these three groups of RNAs interact and build a ceRNA network [28].…”

Genetic influence on treatment outcomes in patients with pain‐related temporomandibular disorders

“…In animal models of neuropathic pain, a linkage was found between long non-coding RNA and microRNA and chronic pain scores. 36 It is possible that the epigenetic approach could be crucial in elucidating the role of genetics in chronic pain conditions.…”

Systematic Review and Meta-Analysis of High-Frequency rTMS over the Dorsolateral Prefrontal Cortex .on Chronic Pain and Chronic-Pain-Accompanied Depression

“…There are some studies showing that chronic pain sensory pathways share the same brain structures involved in emotional management. , The PFC, insular cortex, hippocampus, amygdala, anterior cingulate, and thalamus are the structural basis for the coexistence of chronic pain and depressive symptoms. At the same time, there are many common biochemical mechanisms between chronic pain and depression. − For example, epigenetic mechanisms (including DNA/RNA methylation, histone modifications, and noncoding RNA-mediated regulation) and transcription factors (such as cyclic AMP response element binding proteins and the nuclear factor-kappa-B family) play an important role in the development of chronic pain and depression. ,, Monoamines (such as serotonin, norepinephrine, and dopamine), metabotropic glutamate receptors, ionotropic glutamate receptors (such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N -methyl- d -aspartate receptors), neurotrophic factors (especially brain-derived neurotrophic factor), and neuroinflammatory factors (such as IL-6, IL-1α, IL-1β, and TNF-α) are also involved in the occurrence of chronic pain and depression. ,− Previous research has found that the potential mechanism of rTMS in treating chronic pain and accompanying depression is related to the regulation of these chemical molecular mechanisms; for example, 10 Hz rTMS on the DLPFC could relieve chronic pain and depressive symptoms by modulating the serotonin systems, dopamine, and glutamate. , …”