ArticlePain2017
Nerve injury-induced epigenetic silencing of opioid receptors controlled by DNMT3a in primary afferent neurons.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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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.
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Who cites it
68 citing papers in PubMed, 95 citations in OpenAlex.
- Genome-wide methylation profiling identifies signatures of pain, fatigue and health scores in women with systemic lupus erythematosus.Rheumatology (Oxford, England) · 2026Article
- A Dnmt3a-Mediated Epigenetic Mechanism for Chronic-Pain-Induced Behaviors of Negative Emotion in Mice.Cells · 2026Article
- TET1 downregulation in the dorsal root ganglion and spinal cord is required for short-term sleep disturbance to delay surgical pain recovery.British journal of anaesthesia · 2026Article
- Pain medication and nerve injuries in upper or lower limb-a Swedish national registry study.Pain reports · 2026Article
- Epigenetic, chromatin-associated, and epitranscriptomic regulation in chronic pain: mechanisms and translational prospects.Frontiers in genetics · 2026Review
- κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation.Journal of clinical medicine · 2025Review
- Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.Pediatric research · 2025Article
- [Clinical pharmacology of opioid analgesics].Schmerz (Berlin, Germany) · 2025Review
- Promoter demethylation of cerebellin 2 by ten-eleven translocation 3 contributes to peripheral sensitization in trigeminal neuropathic pain of mice.The journal of headache and pain · 2025Article
- DNMT3a Downregulation Ttriggered Upregulation of GABAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Electroacupuncture alleviates pain-like behaviors through modulating DNMT3a/MOR signaling pathway in CCI rats.PloS one · 2025Article
- Pain - related methylation driver genes affect the prognosis of pancreatic cancer patients by altering immune function and perineural infiltration.Frontiers in genetics · 2025Article
- Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons.Scientific reports · 2024Article
- Opioid and Cannabinoid Systems in Pain: Emerging Molecular Mechanisms and Use in Clinical Practice, Health, and Fitness.International journal of molecular sciences · 2024Review
- Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024Review
- The Epigenetics of Neuropathic Pain: A Systematic Update.International journal of molecular sciences · 2023Review
- POU2F1/DNMT3a Pathway Participates in Neuropathic Pain by Hypermethylation-Mediated LRFN4 Downregulation Following Oxaliplatin Treatment.Neurochemical research · 2023Article
- Narrative Review of the Complex Interaction between Pain and Trauma in Children: A Focus on Biological Memory, Preclinical Data, and Epigenetic Processes.Children (Basel, Switzerland) · 2023Review
- Intraperitoneal 5-Azacytidine Alleviates Nerve Injury-Induced Pain in Rats by Modulating DNA Methylation.Molecular neurobiology · 2023Article
- The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Opioids are the gold standard for pharmacological treatment of neuropathic pain, but their analgesic effects are unsatisfactory in part due to nerve injury-induced downregulation of opioid receptors in dorsal root ganglia (DRG) neurons. How nerve injury drives such downregulation remains elusive. DNA methyltransferase (DNMT)-triggered DNA methylation represses gene expression. We show here that blocking the nerve injury-induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu-opioid receptor (MOR) and kappa-opioid receptor (KOR) proteins in the injured DRG. Blocking this increase also prevented the nerve injury-induced increase in DNA methylation in the promoter and 5'-untranslated region of the Oprm1 gene in the injured DRG, restored morphine or loperamide (a peripheral acting MOR preferring agonist) analgesic effects, and attenuated the development of their analgesic tolerance under neuropathic pain conditions. Mimicking this increase reduced the expression of Oprm1 and Oprk1 mRNAs and their coding MOR and KOR in DRG and augmented MOR-gated neurotransmitter release from the primary afferents. Mechanistically, DNMT3a regulation of Oprm1 gene expression required the methyl-CpG-binding protein 1, MBD1, as MBD1 knockout resulted in the decreased binding of DNMT3a to the Oprm1 gene promoter and blocked the DNMT3a-triggered repression of Oprm1 gene expression in DRG neurons. These data suggest that DNMT3a is required for nerve injury-induced and MBD1-mediated epigenetic silencing of the MOR and KOR in the injured DRG. DNMT3a inhibition may serve as a promising adjuvant therapy for opioid use in neuropathic pain management.
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What OpenQuestion holds
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.