Chronic morphine decreases G9a expression and H3K9me2 at global level and in specific loci in mouse NAc. |
23197736 |
Sun et al., 2012 | [ | 38 | ] |
promoter is measured in response to opioid use, and such epigenetic restructuring can be induced even by short-term use of therapeutic opioids. |
32493461 |
Sandoval-Sierra et al., 2020 | [ | 52 | ] |
Morphine |
Central nucleus of amygdala |
Chromatin immunoprecipitation |
Gene and protein expression |
Remifentanil, oxycodone, codeine | Female mice with persistent and acute pain |
Whole bloodPersistent pain and repeated morphine upregulate the transcriptional regulator MeCP2. MeCP2 enhances |
Pyrosequencing at specific CpG sites and LINE1 (global genome-wide DNA methylation assay) |
DNA methylation |
140 women with persistent pain after breast cancer surgeryBDNF expression and represses G9a action and its repressive mark H3K9me2 in CeA. |
24990928 |
Zhang et al., 2014 [39] |
The global DNA methylation is shown to be a pain predictive biomarker, providing useful information to allocate the patients to either a “persistent pain” or “non-persistent pain” phenotype. |
31775878 |
Kringel et al., 2019 | [ | 53] |
Morphine |
Central nucleus of amygdala |
Chromatin immunoprecipitation |
Gene expression |
Rat model of morphine self-administration |
The repression of GluA1 function by MeCp2 is proposed as a mechanism for morphine-seeking behavior in pain experience. |
25716866 |
Hou et al., 2015 Zhang et al., 2016 [41] |
Morphine |
Dorsal root ganglia |
Quantitative RT-PCR and Western Blot |
Gene and protein expression |
Adult male CD-1 mice |
Neuropathic pain increases C/EBPβ expression. C/EPBβ activates the G9a gene, that epigenetically silences Kv1.2 and MOR genes. Blocking the induced increase in C/EBPβ in the DRG, morphine analgesia after CCI is improved. |
28698219 |
Li et al., 2017 [42] |
Morphine |
Basolateral amygdala |
Quantitative RT-PCR and Western Blot |
Gene and protein expression |
Male Sprague–Dawley |
Increase in H3K14ac together with upregulation of the BDNF and FosB; and CREB activation. |
24829091 |
Wang et al., 2015 [43] |
Morphine |
Rat brain regions |
Pyrosequencing |
DNA methylation (5mC) and global DNA 5-hydroxymethylation (5hmC) |
Opioids |
Whole blood |
Bisulfite modification and Array-based genome-wide DNA methylation assay |
DNA methylation at specific CpG sites |
140 opioid dependence cases and 80 opioid-exposed controls |
Three genome-wide significant differentially methylated CpGs map to genes involved in chromatin remodeling, DNA binding, cell survival, and cell projection (PARG, RERE, and CFAP77 |
[ |
40 | ] |
genes). |
Morphine |
Dorsal root ganglia and spinal cord tissues |
Quantitative RT-PCR, Western Immunoblotting and ChIP-PCR |
Gene and protein expression, histone modifications analysis |
Male Sprague-Dawley rats SNL (spinal nerve ligation) model |
G9a contributes to transcriptional repression of MORs in primary sensory neurons in neuropathic pain. G9a inhibitors: potential treatment of chronic neuropathic pain |
26917724 |
Male Wistar rats |
Acute and chronic exposure is associated with significantly decreased/increased 5mC at specific genes ( | BDNF, IL1B, IL6, NR3C1, COMT | ). Global 5hmC levels increase in the cerebral cortex, hippocampus, and hypothalamus, but decrease in the midbrain. |
29111854 |
Barrow et al., 2017 [44] |
Morphine, phentayl |
Hippocampus |
RNAseq |
Gene and protein expression |
Mice chronically treated with μ-opioid agonists |
The increased expression of MiR-339-3p inhibits intracellular MOR biosynthesis and acts as a negative feedback modulator of MOR signals. |
23085997 |
Wu et al., 2013 [31] |
Morphine |
Dorsal root ganglia |
Quantitative RT-PCR and Western Blot |
Gene and protein expression |
Male CD-1 mice treated with morphine to establish systemic chronic tolerance to morphine anti-nociception |
MiR-219 contributes to the development of chronic tolerance to morphine analgesia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression. |
27599867 |
Hu et al., 2016 [45] |
Morphine |
Dorsal root ganglia |
Quantitative RT-PCR and Western Blot |
Gene and protein expression |
Male CD-1 mice injected with morphine to elicit morphine tolerance |
The increased BDNF expression is regulated by the miR-375 and JAK2/STAT3 pathway. Inhibition of this pathway decreases BDNF production, and thus, attenuated morphine tolerance. |
28603428 |
Li et al., 2017 [46] |
Oxycodone |
Ventral tegmental area of the developing brain |
Quantitative RT-PCR and chromatin immunoprecipitation |
Gene expression and histone modifications analysis |
Male offspring of C57Bl/6NTac mice |
Adolescent oxycodone exposure increases the repressive mark H3K27me3, at key dopamine-related genes. |
33325096 |
Carpenter et al., 2020 [24] |
Oxycodone |
Striatum (NAc and CPu) |
RNAseq |
Gene expression |
Mice following extended 14-day oxycodone self-administration |
Alterations in the expression of heterodimer receptor, integrins, semaphorins, semaphorin receptors, plexins, selective axon guidance genes. |
29946272 |
Yuferov et al., 2018 [47] |
Oxycodone |
Dorsal striatum and ventral striatum |
RNAseq |
Gene expression |
Adult male C57BL/6J mice underwent a 14-day oxycodone self-administration |
Inflammation/immune genes have altered expression during chronic self-administration of oxycodone |
28653080 |
Zhang et al., 2017 [48] |
Oxycodone |
Hippocampus |
DNA ELISA Kit for total 5mC; quantitative RT-PCR |
Global 5mC levels and gene expression |
Male Sprague-Dawley rats |
The global DNA hypomethylation induced by oxycodone can be reversed through oxytocin and could significantly attenuate the oxycodone rewarding effects. |
31526808 |
Fan et al., 2019 [49] |
Oxycodone |
Ventral tegmental area |
DNA ELISA Kit for total 5mC and OneStep qMethyl™ kit for gene-specific 5mC, quantitative RT-PCR, Western blotting |
Global and specific 5mC levels and gene expression |
Sprague-Dawley rats |
Down-regulation of DNMT1 and up-regulation of TET1-3 lead to a decrease in global 5mC levels and differential demethylation at exon 1 of SYN and exon 2 of PSD95. |
31735530 |
Fan et al., 2019 [50] |