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Prescription Opioid Misuse
Prescription opioids are used for some chronic pain conditions. However, generally, long-term therapy has unwanted side effects which may trigger addiction, overdose, and eventually cause deaths. Opioid addiction and chronic pain conditions have both been associated with evidence of genetic and epigenetic alterations. Despite intense research interest, many questions about the contribution of epigenetic changes to this typology of addiction vulnerability and development remain unanswered.
2. Prescription Opioids Pain Relievers
3. Epigenetics and Prescription Opioids
(PAG, PFC, temporal lobe, and ventral striatum)
|Microarray gene expression profiling and pattern matching||Gene expression||Adult male mice||The development of tolerance is influenced by a region in OPRM1 gene. The genes epigenetically modified by chronic morphine administration are mainly related to neuroadaptation.||19386926||Tapocik et al., 2009 |
|Morphine||NAc||Chromatin immunoprecipitation followed by massive parallel sequencing||H3K9me2 distribution in NAc in the absence and presence of chronic morphine||9 to 11-week-old C57BL/6J male mice or G9afl/fl mice||Chronic morphine decreases G9a expression and H3K9me2 at global level and in specific loci in mouse NAc.||23197736||Sun et al., 2012 |
|Morphine||Central nucleus of amygdala||Chromatin immunoprecipitation||Gene and protein expression||Female mice with persistent and acute pain||Persistent pain and repeated morphine upregulate the transcriptional regulator MeCP2. MeCP2 enhances BDNF expression and represses G9a action and its repressive mark H3K9me2 in CeA.||24990928||Zhang et al., 2014 |
|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 |
|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||Zhang et al., 2016 |
|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 |
|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 |
|Morphine||Rat brain regions||Pyrosequencing||DNA methylation (5mC) and global DNA 5-hydroxymethylation (5hmC)||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 |
|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 |
|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 |
|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 |
|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 |
|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 |
|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 |
|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 |
|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 |
|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 genes).||31801960||Montalvo-Ortiz et al., 2019 |
|Opioid medication self-administration (hydrocodone, oxycodone, and codeine: 5–30 mg)||Saliva collected at 3 time points||Genome-wide DNA methylation assay and candidate approach||DNA methylation at OPRM1 gene promoter||33 opioid-naïve participants who underwent standard dental surgery||Hypermethylation of the OPRM1 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 |
|Remifentanil, oxycodone, codeine||Whole blood||Pyrosequencing at specific CpG sites and LINE1 (global genome-wide DNA methylation assay)||DNA methylation||140 women with persistent pain after breast cancer surgery||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 |
The entry is from 10.3390/genes12081226
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