ArticleMolecular pain
Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- A Dnmt3a-Mediated Epigenetic Mechanism for Chronic-Pain-Induced Behaviors of Negative Emotion in Mice.Cells · 2026Article
- Epigenetic and biomolecular mechanisms in chronic temporomandibular disorder-related pain: an integrative review.Molecular biology reports · 2026Review
- Epigenetic, chromatin-associated, and epitranscriptomic regulation in chronic pain: mechanisms and translational prospects.Frontiers in genetics · 2026Review
- Dnmt3a1 regulates hippocampus-dependent memory via the downstream target Nrp1.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites.Cellular and molecular life sciences : CMLS · 2024Article
- Genomic targets and selective inhibition of DNA methyltransferase isoforms.Clinical epigenetics · 2022Article
- Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain.Clinical epigenetics · 2022Article
- Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice.Nature communications · 2022Article
- DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.International journal of molecular sciences · 2022Review
- VEGFD Protects Retinal Ganglion Cells and, consequently, Capillaries against Excitotoxic Injury.Molecular therapy. Methods & clinical development · 2020Article
- Functional Consequences of Calcium-Dependent Synapse-to-Nucleus Communication: Focus on Transcription-Dependent Metabolic Plasticity.Cold Spring Harbor perspectives in biology · 2020Review
- Neuronal ensemble-specific DNA methylation strengthens engram stability.Nature communications · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic pain is a pathological manifestation of neuronal plasticity supported by altered gene transcription in spinal cord neurons that results in long-lasting hypersensitivity. Recently, the concept that epigenetic regulators might be important in pathological pain has emerged, but a clear understanding of the molecular players involved in the process is still lacking. In this study, we linked Dnmt3a2, a synaptic activity-regulated de novo DNA methyltransferase, to chronic inflammatory pain. We observed that Dnmt3a2 levels are increased in the spinal cord of adult mice following plantar injection of Complete Freund's Adjuvant, an in vivo model of chronic inflammatory pain. In vivo knockdown of Dnmt3a2 expression in dorsal horn neurons blunted the induction of genes triggered by Complete Freund's Adjuvant injection. Among the genes whose transcription was found to be influenced by Dnmt3a2 expression in the spinal cord is Ptgs2, encoding for Cox-2, a prime mediator of pain processing. Lowering the levels of Dnmt3a2 prevented the establishment of long-lasting inflammatory hypersensitivity. These results identify Dnmt3a2 as an important epigenetic regulator needed for the establishment of central sensitization. Targeting expression or function of Dnmt3a2 may be suitable for the treatment of chronic pain.
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