ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
HDAC4 is required for inflammation-associated thermal hypersensitivity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities.Biomolecules · 2025Review
- Histone deacetylases: the critical enzymes for microglial activation involved in neuropathic pain.Frontiers in pharmacology · 2025Review
- Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury-induced neuropathy in rats.Pain reports · 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
- Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study.Clinical epigenetics · 2023Article
- Role of Epigenetic Mechanisms in Chronic Pain.Cells · 2022Review
- Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice.Nature communications · 2022Article
- Catalpol ameliorates CFA-induced inflammatory pain by targeting spinal cord and peripheral inflammation.Frontiers in pharmacology · 2022Article
- Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.Pharmacology & therapeutics · 2021Review
- Non-coding RNAs in neuropathic pain.Neuronal signaling · 2020Review
- MiR-206-3p alleviates chronic constriction injury-induced neuropathic pain through targeting HDAC4.Experimental animals · 2019Article
- Article
- Drugging the pain epigenome.Nature reviews. Neurology · 2017Review
- Drosophila caspase activity is required independently of apoptosis to produce active TNF/Eiger during nociceptive sensitization.Cell death & disease · 2017Article
- Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain.Scientific reports · 2017Article
- SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain.Molecular painArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Transcriptional alterations are characteristic of persistent pain states, but the key regulators remain elusive. HDAC4 is a transcriptional corepressor that has been linked to synaptic plasticity and neuronal excitability, mechanisms that may be involved in peripheral and central sensitization. Using a conditional knockout (cKO) strategy in mice, we sought to determine whether the loss of HDAC4 would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely unnecessary for transcriptional regulation of naïve sensory neurons but was essential for appropriate transcriptional responses after injury, with Calca and Trpv1 expression consistently down-regulated in HDAC4 cKO compared to levels in the littermate controls (0.2-0.44-fold change, n = 4 in 2 separate experiments). This down-regulation corresponded to reduced sensitivity to 100 nM capsaicin in vitro (IC50 = 230 ± 20 nM, 76 ± 4.4% wild-type capsaicin responders vs. 56.9 ± 4.7% HDAC4 cKO responders) and to reduced thermal hypersensitivity in the complete Freund's adjuvant (CFA) model of inflammatory pain (1.3-1.4-fold improvement over wild-type controls; n = 5-12, in 2 separate experiments). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors.
Indexed as
Identifiers
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.