ArticleThe Journal of biological chemistry2012
Methylglyoxal activates nociceptors through transient receptor potential channel A1 (TRPA1): a possible mechanism of metabolic neuropathies.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
What it found
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The trial behind it
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Who cites it
94 citing papers in PubMed, 186 citations in OpenAlex.
- Proof of Pharmacology, Safety, and Pharmacokinetics of the Novel TRPA1 Antagonist BI 1839100: A Randomized, Placebo-Controlled, Parallel Group, First-In-Human Study in Healthy Male Participants.Clinical and translational science · 2025Trial
- A Human TRPA1-Specific Pain Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Trial
- 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
- Elucidating the Urothelial-Dependent and -Independent Mechanisms Involved in the Mouse Bladder Contractility Alterations by Acute Methylglyoxal Exposure.Biomedicines · 2026Article
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- Deep learning identifies TP-41 for methylglyoxal scavenging in Alzheimer's treatment.Theranostics · 2026Article
- Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain.International journal of molecular sciences · 2025Review
- Article
- Diroximel Fumarate Acts Through Nrf2 to Attenuate Methylglyoxal-Induced Nociception in Mice and Decrease ISR Activation in DRG Neurons.Diabetes · 2025Article
- Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel.ChemMedChem · 2025Article
- Methylglyoxal impairs human dermal fibroblast survival and migration by alteringToxicology reports · 2024Article
- Genetic Variants Influence the Development of Diabetic Neuropathy.International journal of molecular sciences · 2024Review
- Thermal gradient ring for analysis of temperature-dependent behaviors involving TRP channels in mice.The journal of physiological sciences : JPS · 2024Review
- 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
- Transient Receptor Potential Ankyrin 1 (TRPA1) Channel Mediates Acrolein Cytotoxicity in Human Lung Cancer Cells.International journal of molecular sciences · 2023Article
- TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy.Brain : a journal of neurology · 2023Article
- Inflammation-the role of TRPA1 channel.Frontiers in physiology · 2023Review
- TRPA1-dependent and -independent activation by commonly used preservatives.Frontiers in pharmacology · 2023Article
34 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 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic pain can develop as an agonizing sequela of diabetes mellitus and chronic uremia. A chemical link between both conditions of altered metabolism is the highly reactive compound methylglyoxal (MG), which accumulates in all cells, in particular neurons, and leaks into plasma as an index of the severity of the disorder. The electrophilic structure of this cytotoxic ketoaldehyde suggests TRPA1, a receptor channel deeply involved in inflammatory and neuropathic pain, as a molecular target. We demonstrate that extracellularly applied MG accesses specific intracellular binding sites of TRPA1, activating inward currents and calcium influx in transfected cells and sensory neurons, slowing conduction velocity in unmyelinated peripheral nerve fibers, and stimulating release of proinflammatory neuropeptides from and action potential firing in cutaneous nociceptors. Using a model peptide of the N terminus of human TRPA1, we demonstrate the formation of disulfide bonds based on MG-induced modification of cysteines as a novel mechanism. In conclusion, MG is proposed to be a candidate metabolite that causes neuropathic pain in metabolic disorders and thus is a promising target for medicinal chemistry.
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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.