ArticleEMBO reports2023
Defective branched-chain amino acid catabolism in dorsal root ganglia contributes to mechanical pain.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- A dual role of PIEZO2 in neuropathic pain: driving peripheral sensitization and enabling mechanical loading-induced analgesia.Cell communication and signaling : CCS · 2026Article
- Piezo2 Mediates a Vicious Cycle of "Mechanical Homeostasis Imbalance-Inflammation" in Sensory Nerves and the Cartilage Endplate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- Neuronal metabolism role in ketogenic diet improvements in bortezomib-induced painful peripheral neuropathy mouse model.Pain reports · 2026Article
- Impaired BCAA Catabolism Contributes To Acute Lung Injury By Triggering Oxidative Stress and Inflammatory Response Via the MAPK Pathway.Inflammation · 2026Article
- Histone Lactylation Contributes to Neuropathic Pain by Facilitating mThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Histone H3 Lysine 18 Lactylation Promotes Cardiac Hypertrophy Through Activating GATA Binding Protein 4 Signaling.MedComm · 2025Article
- Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome.American journal of physiology. Cell physiology · 2025Article
- Pain mechanisms in osteoarthritis: recent discoveries and opportunities ahead.Connective tissue research · 2025Review
- Histone and non-histone lactylation: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Phosphatase activity-based PPM1K: a key player in the regulation of mitochondrial function and its multifaceted impact in diseases.Molecular and cellular biochemistry · 2025Review
- Lactate alleviates trigeminal neuralgia symptoms in mice by suppressing neuroinflammation.The Journal of international medical research · 2025Article
- Lactylation-Driven HECTD2 Limits the Response of Hepatocellular Carcinoma to Lenvatinib.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
- Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.EMBO reports · 2024Article
- Protein phosphatase 2Cm-regulated branched-chain amino acid catabolic defect in dorsal root ganglion neurons drives pain sensitization.Acta neuropathologica communications · 2024Article
- Defective branched-chain amino acid catabolism in dorsal root ganglia contributes to mechanical pain.EMBO reports · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the underlying molecular mechanisms are unclear. Here, we report that defective BCAA catabolism in dorsal root ganglion (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and expression of the mechanotransduction channel Piezo2. In high-fat diet-fed obese mice, we observed the downregulation of PP2Cm, a key regulator of the BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons exhibit mechanical allodynia under normal or SNI-induced neuropathic injury conditions. Furthermore, the VAS scores in the plasma of patients with peripheral neuropathic pain are positively correlated with BCAA contents. Mechanistically, defective BCAA catabolism in DRG neurons promotes lactate production through glycolysis, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or Piezo2 silencing attenuates the pain phenotype of knockout mice in response to mechanical stimuli. Therefore, our study demonstrates a causal role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.
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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.