ArticleNature medicine2011
Epigenetic suppression of GAD65 expression mediates persistent pain.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01928849 (Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain), which is not on this map. Cited by 146 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.
Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain
Who cites it
146 citing papers in PubMed, 288 citations in OpenAlex.
- A Dnmt3a-Mediated Epigenetic Mechanism for Chronic-Pain-Induced Behaviors of Negative Emotion in Mice.Cells · 2026Article
- Epigenetics in anesthesiology: an overview and clinical relevance.Anesthesia and pain medicine · 2026Review
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- Neurophysiological Basis of Short-Chain Fatty Acid Action in Pain Modulation: Therapeutic Implications.International journal of molecular sciences · 2025Review
- Article
- Mechanisms for Orofacial Pain: Roles of Immunomodulation, Metabolic Reprogramming, Oxidative Stress and Epigenetic Regulation.Biomedicines · 2025Review
- Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury-induced neuropathy in rats.Pain reports · 2024Article
- Critical Windows: Exploring the Association Between Perinatal Trauma, Epigenetics, and Chronic Pain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- The effect of intra spinal administration of cerium oxide nanoparticles on central pain mechanism: An experimental study.Journal of bioenergetics and biomembranes · 2024Article
- Directions for analgesic development.Journal of anesthesia and translational medicine · 2024Review
- Epigenetic Regulation and Molecular Mechanisms of Burn Injury-Induced Nociception in the Spinal Cord of Mice.International journal of molecular sciences · 2024Article
- HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.Inflammopharmacology · 2024Review
- Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.International journal of molecular sciences · 2024Review
- CBP Expression Contributes to Neuropathic Pain via CREB and MeCP2 Regulation in the Spared Nerve Injury Rat Model.Medicina (Kaunas, Lithuania) · 2024Article
- Histone deacetylase as emerging pharmacological therapeutic target for neuropathic pain: From epigenetic to selective drugs.CNS neuroscience & therapeutics · 2024Review
- Epigenetic HDAC5 Inhibitor Reverses Craniofacial Neuropathic Pain in Mice.The journal of pain · 2024Article
- Potential Therapeutic Effects of Short-Chain Fatty Acids on Chronic Pain.Current neuropharmacology · 2024Review
- Terahertz Wave Alleviates Comorbidity Anxiety in Pain by Reducing the Binding Capacity of Nanostructured Glutamate Molecules to GluA2.Research (Washington, D.C.) · 2024Article
- The Epigenetics of Neuropathic Pain: A Systematic Update.International journal of molecular sciences · 2023Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chronic pain is a common neurological disease involving lasting, multifaceted maladaptations ranging from gene modulation to synaptic dysfunction and emotional disorders. Sustained pathological stimuli in many diseases alter the output activities of certain genes through epigenetic modifications, but it is unclear how epigenetic mechanisms operate in the development of chronic pain. We show here that in the rat brainstem nucleus raphe magnus, which is important for central mechanisms of chronic pain, persistent inflammatory and neuropathic pain epigenetically suppresses Gad2 (encoding glutamic acid decarboxylase 65 (GAD65)) transcription through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in impaired γ-aminobutyric acid (GABA) synaptic inhibition. Gad2 knockout mice showed sensitized pain behavior and impaired GABA synaptic function in their brainstem neurons. In wild-type but not Gad2 knockout mice, HDAC inhibitors strongly increased GAD65 activity, restored GABA synaptic function and relieved sensitized pain behavior. These findings suggest GAD65 and HDACs as potential therapeutic targets in an epigenetic approach to the treatment of chronic pain.
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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.