Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin

Abstract

Untargeted metabolomics reveals a dysregulation of sphingolipid production during neuropathic pain exemplified by N,N-dimethylsphingosine, whose upregulation is involved in the generation of pain. 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.