ArticleNature medicine2012
Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 245 papers.
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Who cites it
245 citing papers in PubMed, 489 citations in OpenAlex.
- Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes.Molecular metabolism · 2018Trial
- Metabolic targeting by a small extracellular vesicle-based cellulose-GelMA hydrogel restores neurovascular regeneration in diabetic nerve injury.Bioactive materials · 2027Article
- Regulation of PDH via cysteine oxidation on DLAT.Nature communications · 2026Article
- Article
- Reactive aldehyde species-mediated neuropathic pain in spinal cord injury: Mechanisms and therapeutic opportunities.Neural regeneration research · 2026Article
- Glyoxalase 1 loss reduces fatty liver but impairs glucose handling in male mice.Physiological reports · 2026Article
- Complex Contributions of Methylglyoxal to Pain, Axon Degeneration, and Diabetic Peripheral Neuropathy.Journal of neurochemistry · 2026Review
- Microbiota and Methylglyoxal-Derived AGEs: Implications in Ageing and Age-Related Disease.Life (Basel, Switzerland) · 2026Review
- Plantar fascia thickness in type 1 diabetes mellitus patients: Clinical associations and metabolic correlates.Journal of diabetes investigation · 2026Article
- Methylglyoxal alters C-fibre activity-dependent slowing and induces heat hyperalgesia in a sex-dependent manner, in rats.Pain reports · 2026Article
- The Excelsatoxin A-Receptor TMEM233 Modulates Nav1.8.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeting TRPA1 with Novel Synthetic Compounds Based on Different Scaffolds to Reduce Acute and Chronic Pain.International journal of molecular sciences · 2026Article
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- The intrinsic reason why the term "central sensitization" should be refined, by introducing the terms "spinal sensitization", "pain-related brain network sensitization", and "psychosocial-related sensitization".Frontiers in pain research (Lausanne, Switzerland) · 2026Article
- Eukaryotic initiation factor 3d Regulates Context-Dependent Pain Hypersensitivity Through the Integrated Stress Response.bioRxiv : the preprint server for biology · 2025Article
- Endoplasmic Reticulum Stress Mediates Axon Initial Segment Shortening: Implications for Diabetic Brain Complications.Journal of molecular neuroscience : MN · 2025Article
- Glyoxalase 1 is a proadipogenic gene.The Journal of biological chemistry · 2025Article
- Article
- A Chemical Mechanistic Path Leads the Way to Cellular Argpyrimidine.Journal of the American Chemical Society · 2025Article
- [Diabetes mellitus-a risk factor for pain].Schmerz (Berlin, Germany) · 2025Review
185 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Commented on by
- Erratum issuedLasischka, Felix [corrected to Lasitschka, Felix]
Authors and funding
34 authors at 14 institutions in 6 countries.
Funding
Abstract
This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na(v)1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy.
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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.