Johnson Caroline H, Patti Gary J, Courade Jean-Philippe, Shriver Leah P, Hoang Linh T, Manchester Marianne, Siuzdak Gary
Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
J Neuroimmune Pharmacol. 2015 Sep;10(3):396-401. doi: 10.1007/s11481-015-9624-y. Epub 2015 Aug 2.
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.
在过去20年中,神经性疼痛的治疗选择有所改善,但仍只能提供部分缓解,且伴有众多副作用。最近,代谢组学研究表明,在神经性疼痛模型中,内源性代谢物N,N-二甲基鞘氨醇(DMS)在脊髓中的浓度会升高。此外,研究还表明,将DMS引入中枢神经系统(CNS)会导致机械性异常性疼痛。在此,我们研究了两种化合物:用于治疗神经性疼痛的药物普瑞巴林(乐瑞卡®),以及一种已知会影响多种脂质途径的内源性类大麻素样化合物N-油酰乙醇胺(NOE)。我们发现,对患有神经性疼痛的大鼠进行普瑞巴林治疗后,脊髓中DMS的浓度没有显著变化。我们进一步探索了调节脂质代谢是否可能通过测试NOE作为一种潜在的新型疗法来影响神经性疼痛。