title: 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.
authors.affiliation: Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Johnson
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Patti
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Courade
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
authors.forename: Linh T
authors.initials: LT
authors.lastname: Hoang
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D055432:Metabolomics; D009437:Neuralgia / Q000188:drug therapy*; D009829:Oleic Acids / Q000494:pharmacology*; D000069583:Pregabalin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000700:Analgesics; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; C033595:N-oleoylethanolamine; D000069583:Pregabalin; C061800:N,N-dimethylsphingosine; D013110:Sphingosine