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Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain

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Abstract

Therapeutic options for neuropathic pain have improved over the last 20 years yet still only provide partial relief with numerous side effects. Recently, metabolomics revealed that the concentration of the endogenous metabolite N,N-dimethylsphingosine (DMS) is increased in the spinal cord in a model of neuropathic pain. Additionally, it was shown that introduction of DMS to the central nervous system (CNS) resulted in mechanical allodynia. Here, we have examined two compounds; pregabalin (Lyrica®), a drug used to treat neuropathic pain, and N-oleoylethanolamine (NOE), an endogenous endocannabinoid-like compound that is known to affect multiple lipid pathways. We found that the concentration of DMS in the spinal cord was not significantly altered upon pregabalin treatment of rats suffering from neuropathic pain. We further explored whether modulating lipid metabolism may impact neuropathic pain by testing NOE as a potential novel therapeutic.

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Funding

This work was supported by US National Institutes of Health grants R01 CA170737 (G.S.), P30 MH062261 (G.S.), RC1 HL101034 (G.S.), P01 DA026146 (G.S.).

Conflict of Interest

The authors declare no conflicts of interest.

Ethical Approval

Research animals were maintained according to institutional animal care and use committee (IACUC) guidelines. This article does not contain any studies with human participants performed by any of the authors.

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Authors and Affiliations

  1. Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Caroline H. Johnson, Linh T. Hoang & Gary Siuzdak

  2. Departments of Chemistry, Genetics and Medicine, Washington University, St. Louis, MO, 63130, USA

    Gary J. Patti

  3. UCB Biopharma, UCB New Medicines, Chemin du Foriest, 1420, Braine-l’Alleud, Belgium

    Jean-Philippe Courade

  4. Departments of Chemistry and Biology, University of Akron, Akron, OH, 44325, USA

    Leah P. Shriver

  5. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA

    Marianne Manchester

  6. Departments of Chemistry, Molecular, and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Gary Siuzdak

Authors
  1. Caroline H. Johnson
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  2. Gary J. Patti
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  3. Jean-Philippe Courade
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  4. Leah P. Shriver
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  5. Linh T. Hoang
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  6. Marianne Manchester
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  7. Gary Siuzdak
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Corresponding author

Correspondence to Gary Siuzdak.

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Johnson, C.H., Patti, G.J., Courade, JP. et al. Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain. J Neuroimmune Pharmacol 10, 396–401 (2015). https://doi.org/10.1007/s11481-015-9624-y

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  • DOI: https://doi.org/10.1007/s11481-015-9624-y

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