ArticlePain2019
Activation of the integrated stress response in nociceptors drives methylglyoxal-induced pain.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 68 citations in OpenAlex.
- Complex Contributions of Methylglyoxal to Pain, Axon Degeneration, and Diabetic Peripheral Neuropathy.Journal of neurochemistry · 2026Review
- Review
- Methylglyoxal alters C-fibre activity-dependent slowing and induces heat hyperalgesia in a sex-dependent manner, in rats.Pain reports · 2026Article
- Endoplasmic Reticulum Stress Mediates Axon Initial Segment Shortening: Implications for Diabetic Brain Complications.Journal of molecular neuroscience : MN · 2025Article
- GCN2 regulates paclitaxel-induced neuropathic pain.British journal of pharmacology · 2025Article
- Article
- Article
- Long-lasting and fast methylglyoxal-scavenging peptide CycK(Myr)RPain reports · 2025Article
- The mRNA Translation Inhibitor Vioprolide A Prevents Inflammatory Pain-Like Behaviour With Limited Action on Already Established Pain-Like Behaviour in Mice.European journal of pain (London, England) · 2025Article
- Diroximel Fumarate Acts Through Nrf2 to Attenuate Methylglyoxal-Induced Nociception in Mice and Decrease ISR Activation in DRG Neurons.Diabetes · 2025Article
- eEF2K regulates pain through translational control of BDNF.Molecular cell · 2025Article
- Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells.Nature communications · 2025Article
- Inhibition of Nonsense-Mediated Decay in Dorsal Root Ganglion Neurons.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.Frontiers in neurology · 2025Review
- Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.Current medicinal chemistry · 2025Review
- Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes.bioRxiv : the preprint server for biology · 2024Article
- Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System.Life (Basel, Switzerland) · 2024Review
- Highly specific σProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons.bioRxiv : the preprint server for biology · 2023Article
- Highly specific σbioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Methylglyoxal (MGO) is a reactive glycolytic metabolite associated with painful diabetic neuropathy at plasma concentrations between 500 nM and 5 μM. The mechanisms through which MGO causes neuropathic pain at these pathological concentrations are not known. Because MGO has been linked to diabetic neuropathic pain, which is prevalent and poorly treated, insight into this unsolved biomedical problem could lead to much needed therapeutics. Our experiments provide compelling evidence that ∼1-μM concentrations of MGO activate the integrated stress response (ISR) in IB4-positive nociceptors in the dorsal root ganglion (DRG) of mice in vivo and in vitro. Blocking the integrated stress response with a specific inhibitor (ISRIB) strongly attenuates and reverses MGO-evoked pain. Moreover, ISRIB reduces neuropathic pain induced by diabetes in both mice and rats. Our work elucidates the mechanism of action of MGO in the production of pain at pathophysiologically relevant concentrations and suggests a new pharmacological avenue for the treatment of diabetic and other types of MGO-driven neuropathic pain.
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What Socratic 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 Socratic graph.