Gaining insight into pain (original) (raw)

Metabolomics

Nature Reviews Drug Discovery volume 11, pages 188–189 (2012)Cite this article

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In a well-established rat model of neuropathic pain — tibial nerve transection (TNT) — allodynia (pain in response to light touch) persists for at least 9 weeks after the initial transection of the tibial branch of the sciatic nerve, despite the wound appearing healed. Patti and colleagues took an untargeted mass spectrometry-based metabolomics approach to analyse metabolites from plasma, the tibial nerve, dorsal root ganglia and the rat dorsal horn of TNT rats and control (sham-operated) animals 21 days after surgery. A total of 733 metabolic features showed over a twofold change between the two groups, and 94% of these were derived from the dorsal horn.

Focusing on this site, where the damaged nerve meets the spinal cord, the authors discovered that sphingomyelin–ceramide metabolism was markedly affected. In particular, levels of ceramide (d18:1) and several phosphatidylcholines were increased, whereas those of several diacylglycerols were decreased, consistent with an increased degradation of sphingomyelin to ceramide. N,_N_-dimethylsphingosine (DMS) was one of several sphingomyelin–ceramide metabolites that were significantly upregulated.

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ORIGINAL RESEARCH PAPER

  1. Patti, G. J. et al. Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nature Chem. Biol. 22 Jan 2012 (doi:10.1038/nchembio.767)

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Legg, K. Gaining insight into pain.Nat Rev Drug Discov 11, 188–189 (2012). https://doi.org/10.1038/nrd3685

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