Abstract
Accumulating evidence suggests that epigenetic alterations lie behind the induction and maintenance of neuropathic pain. Neuropathic pain is usually a chronic condition caused by a lesion, or pathological change, within the nervous system. Neuropathic pain appears frequently after nerve and spinal cord injuries or diseases, producing a debilitation of the patient and a decrease of the quality of life. At the cellular level, neuropathic pain is the result of neuronal plasticity shaped by an increase in the sensitivity and excitability of sensory neurons of the central and peripheral nervous system. One of the mechanisms thought to contribute to hyperexcitability and therefore to the ontogeny of neuropathic pain is the altered expression, trafficking, and functioning of receptors and ion channels expressed by primary sensory neurons. Besides, neuronal and glial cells, such as microglia and astrocytes, together with blood borne macrophages, play a critical role in the induction and maintenance of neuropathic pain by releasing powerful neuromodulators such as pro-inflammatory cytokines and chemokines, which enhance neuronal excitability. Altered gene expression of neuronal receptors, ion channels, and pro-inflammatory cytokines and chemokines, have been associated to epigenetic adaptations of the injured tissue. Within this review, we discuss the involvement of these epigenetic changes, including histone modifications, DNA methylation, non-coding RNAs, and alteration of chromatin modifiers, that have been shown to trigger modification of nociception after neural lesions. In particular, the function on these processes of EZH2, JMJD3, MeCP2, several histone deacetylases (HDACs) and histone acetyl transferases (HATs), G9a, DNMT, REST and diverse non-coding RNAs, are described. Despite the effort on developing new therapies, current treatments have only produced limited relief of this pain in a portion of patients. Thus, the present review aims to contribute to find novel targets for chronic neuropathic pain treatment.
Highlights
Neuropathic pain appears as a consequence of a lesion or disease affecting the central nervous system (CNS) or peripheral nervous system (PNS) (Freynhagen and Bennett, 2009)
Several studies demonstrated that the increased expression of CCL2, CCL3, MiP-2, CXCR2, and CXCR1/CXRR5 were suppressed by the histone acetyl transferases (HATs) inhibitor anacardic acid, suggesting that these chemokines are upregulated through histone acetylation of H3K9
A study demonstrated that the specific knockout of euchromatic histone-lysine N-methyltransferase (G9a) in sensory neurons of the dorsal root ganglia (DRG) blocked gene silencing of potassium channels (Table 4) and the promotion of neuropathic pain after peripheral nerve lesion (Laumet et al, 2015)
Summary
Neuropathic pain appears as a consequence of a lesion or disease affecting the CNS or PNS (Freynhagen and Bennett, 2009). We describe the major epigenetic enzyme alterations observed after traumatic neural injuries that affect the expression of pro-inflammatory neuromodulators, and intrinsic neuronal excitability, promoting neuropathic pain. Epigenetic enzymes contribute to create chemical mediator promoter accessibility to the transcription machinery, enhancing gene expression Inhibition of these enzymes has been described to produce a decrease of inflammation as well as neuropathic pain. Genome or micro-array data of several investigations report that microRNAs are differentially regulated in neuropathic pain models in DRG neurons, sciatic nerve, spinal cord and nucleus accumbens
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
