ArticleMolecular and cellular biology2007
Evidence of endogenous mu opioid receptor regulation by epigenetic control of the promoters.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04031716 (Genetic, Epigenetic, Psychosocial, and Biological Determinants of Post-surgical Pain After Pectus or Spine Surgery), which is not on this map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic, Epigenetic, Psychosocial, and Biological Determinants of Post-surgical Pain After Pectus or Spine Surgery
Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
- Hypermethylation of OPRM1: Deregulation of the Endogenous Opioid Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.International journal of molecular sciences · 2026Article
- Genetic and Epigenetic Approaches to Opioid Use Disorder.Expert reviews in molecular medicine · 2025Review
- Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.Pediatric research · 2025Article
- Opioids and Cancer: Current Understanding and Clinical Considerations.Current oncology (Toronto, Ont.) · 2024Review
- No significant change of NBrain and behavior · 2024Article
- Lactobacillus rhamnosus GG and butyrate supplementation in rats with bone cancer reduces mechanical allodynia and increases expression of μ-opioid receptor in the spinal cord.Frontiers in molecular neuroscience · 2023Article
- Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.International journal of molecular sciences · 2022Review
- Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer.Journal of pain research · 2022Review
- Epigenetic and Genetic Factors Associated With Opioid Use Disorder: Are These Relevant to African American Populations.Frontiers in pharmacology · 2021Review
- Article
- Who's your daddy? Behavioral and epigenetic consequences of paternal drug exposure.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2019Review
- The Mechanisms Involved in Morphine Addiction: An Overview.International journal of molecular sciences · 2019Review
- Comparison of Different Histone Deacetylase Inhibitors in Attenuating Inflammatory Pain in Rats.Pain research & management · 2019Article
- Overexpression of µ-Opioid Receptors in Peripheral Afferents, but Not in Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances Opioid Analgesia in Mouse.Anesthesiology · 2018Article
- Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.Frontiers in pharmacology · 2018Article
- mPer1 promotes morphine-induced locomotor sensitization and conditioned place preference via histone deacetylase activity.Psychopharmacology · 2017Article
- Epigenetic Activation ofMolecular pharmacology · 2017Article
- Post-Transcriptional Regulation of the Human Mu-Opioid Receptor (MOR) by Morphine-Induced RNA Binding Proteins hnRNP K and PCBP1.Journal of cellular physiology · 2017Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The pharmacological effect of morphine as a painkiller is mediated mainly via the mu opioid receptor (MOR) and is dependent on the number of MORs in the cell surface membrane. While several studies have reported that the MOR gene is regulated by various cis- and trans-acting factors, many questions remain unanswered regarding in vivo regulation. The present study shows that epigenetic silencing and activation of the MOR gene are achieved through coordinated regulation at both the histone and DNA levels. In P19 mouse embryonal carcinoma cells, expression of the MOR was greatly increased after neuronal differentiation. MOR expression could also be induced by a demethylating agent (5'-aza-2'-deoxycytidine) or histone deacetylase inhibitors in the P19 cells, suggesting involvement of DNA methylation and histone deacetylation for MOR gene silencing. Analysis of CpG DNA methylation revealed that the proximal promoter region was unmethylated in differentiated cells compared to its hypermethylation in undifferentiated cells. In contrast, the methylation of other regions was not changed in either cell type. Similar methylation patterns were observed in the mouse brain. In vitro methylation of the MOR promoters suppressed promoter activity in the reporter assay. Upon differentiation, the in vivo interaction of MeCP2 was reduced in the MOR promoter region, coincident with histone modifications that are relevant to active transcription. When MeCP2 was disrupted using MeCP2 small interfering RNA, the endogenous MOR gene was increased. These data suggest that DNA methylation is closely linked to the MeCP2-mediated chromatin structure of the MOR gene. Here, we propose that an epigenetic mechanism consisting of DNA methylation and chromatin modification underlies the cell stage-specific mechanism of MOR gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.