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Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain.

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.
AuthorsCaroline H Johnson, Gary J Patti, Jean-Philippe Courade, Leah P Shriver, Linh T Hoang, Marianne Manchester, Gary Siuzdak
JournalJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (J Neuroimmune Pharmacol) Vol. 10 Issue 3 Pg. 396-401 (Sep 2015) ISSN: 1557-1904 [Electronic] United States
PMID26232265 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Analgesics
  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Ethanolamines
  • Oleic Acids
  • N-oleoylethanolamine
  • Pregabalin
  • N,N-dimethylsphingosine
  • Sphingosine
Topics
  • Analgesics (pharmacology)
  • Animals
  • Cannabinoid Receptor Agonists (pharmacology)
  • Disease Models, Animal
  • Endocannabinoids (pharmacology)
  • Ethanolamines (pharmacology)
  • Male
  • Metabolomics
  • Neuralgia (drug therapy)
  • Oleic Acids (pharmacology)
  • Pregabalin (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Sphingosine (analogs & derivatives, metabolism)
  • Spinal Cord (drug effects, metabolism)

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