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Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin

Nature Chemical Biology volume 8, pages 232–234 (2012)Cite this article

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Abstract

Neuropathic pain is a debilitating condition for which the development of effective treatments has been limited by an incomplete understanding of its chemical basis. We show by using untargeted metabolomics that sphingomyelin-ceramide metabolism is altered in the dorsal horn of rats with neuropathic pain and that the upregulated, endogenous metabolite N,N-dimethylsphingosine induces mechanical hypersensitivity in vivo. These results demonstrate the utility of metabolomics to implicate unexplored biochemical pathways in disease.

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Figure 1: Untargeted metabolomics identifies the dysregulation of sphingomyelin-ceramide metabolism in the ipsilateral dorsal horn during chronic neuropathic pain.
Figure 2: DMS elicits neuropathic pain behavior and cytokine release.

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Acknowledgements

This work was supported by the US National Institutes of Health (NIH) R24 EY017540-04 (G.S.), P30 MH062261 (M.M., G.S.) and P01 DA026146-02 (G.S.) in addition to RR025774 (M.M.); NIH–National Institute of Aging L30 AG0 038036 (G.J.P.); and NIH–National Institute of Neurological Disorders and Stroke F32NS068015 and T32 NSO41219 (L.P.S.). We also acknowledge financial support from the US Department of Energy FG02-07ER64325 and DE-AC0205CH11231).

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Author notes

  1. Jean-Phillipe Courade

    Present address: Current address: UCB Pharma, Chemin du Foriest, Braine-L'Alleud, Belgium.,

Authors and Affiliations

  1. Department of Chemistry, Washington University School of Medicine, St. Louis, Missouri, USA

    Gary J. Patti

  2. Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA

    Gary J. Patti

  3. Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Gary J. Patti

  4. Department of Chemistry, Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, California, USA

    Oscar Yanes, Ralf Tautenhahn & Gary Siuzdak

  5. Department of Molecular Biology, Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, California, USA

    Oscar Yanes, Ralf Tautenhahn & Gary Siuzdak

  6. The Metabolomics Platform of the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, Rovira i Virgili University, Taragona, Spain

    Oscar Yanes

  7. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego, La Jolla, California, USA

    Leah P Shriver & Marianne Manchester

  8. Pain Research Unit, Pfizer Global Research and Development, Kent, UK

    Jean-Phillipe Courade

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  1. Gary J. Patti
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Contributions

G.J.P. and O.Y. contributed equally to this work. G.J.P., L.P.S. and J.C. performed work on rats. G.J.P., O.Y. and L.P.S. performed analytical experiments. G.J.P., O.Y., L.P.S., J.-P.C., R.T., M.M. and G.S. contributed to experimental design, performed data analysis and wrote the manuscript.

Corresponding authors

Correspondence to Marianne Manchester or Gary Siuzdak.

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The authors declare no competing financial interests.

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Patti, G., Yanes, O., Shriver, L. et al. Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat Chem Biol 8, 232–234 (2012). https://doi.org/10.1038/nchembio.767

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