Summary of project PR001731

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001731. The data can be accessed directly via it's Project DOI: 10.21228/M8ZD8R This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001731
Project DOI:doi: 10.21228/M8ZD8R
Project Title:Defective Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia Contributes to Mechanical Pain
Project Summary:Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the molecular mechanisms are unclear. Here we report that defective BCAA catabolism in dorsal root ganglia (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and Piezo2 expression, a mechanotransduction channel. In high-fat diet fed obese mice, we observed a downregulation of PP2Cm, a key regulator in BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons (cKO) exhibited mechanical allodynia under normal or spare nerve injury (SNI)-induced neuropathic injury conditions. Further, in patients with peripheral neuropathic pain, we found that the Visual Analogue Scale (VAS) scores were positively correlated with BCAA contents in plasma, highlighting a link between peripheral neuropathic pain and dysregulated BCAA catabolism. Mechanistically, defective BCAA catabolism promotes the production of lactate through glycolysis in DRG neurons, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or silencing of Piezo2 expression attenuated the pain phenotype of cKO to mechanical stimuli. Therefore, our study demonstrates a casual role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.
Institute:West China Hospital of Sichuan University
Laboratory:Laboratory of Mitochondria and Metabolism
Last Name:Li
First Name:Tao
Address:No. 37 Guoxue Road, Wuhou District, Chendu 610041, Sichuan, China

Summary of all studies in project PR001731

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002774 Metabolomics studies on L4-5 Dorsal Root Ganglia of Ctrl and cKO mice Mus musculus West China Hospital of Sichuan University MS 2023-09-14 1 12 Uploaded data (3.6M)*