Fighting Neuropathic Pain | January 23, 2012 Issue - Vol. 90 Issue 4 | Chemical & Engineering News
Volume 90 Issue 4 | p. 8 | News of The Week
Issue Date: January 23, 2012

Fighting Neuropathic Pain

Metabolomics: Researchers discover a metabolite associated with chronic pain from tissue injury
Department: Science & Technology
News Channels: Biological SCENE
Keywords: neuropathic pain, metabolomics, LC/MS
Assistant professor of genetics Gary J. Patti of Washington University School of Medicine, St. Louis, first author of the Nature Chemical Biology paper on a newly discovered chemical cause of neuropathic pain, describes the group’s study, which was conducted at The Scripps Research Institute. Patti was a research associate at Scripps during the study.
Credit: Filmed and edited by Aaron Rowe for C&EN

The overproduction of a previously unknown endogenous metabolite called N,N-dimethylsphingosine (DMS) in injured tissues may be a key cause of a condition called neuropathic pain, according to a Nature Chemical Biology report (DOI: 10.1038/nchembio.767). The findings, which identify DMS production as a potential novel target to which inhibitors might be directed, could lead to more effective drugs to treat the condition.

Neuropathic pain is a chronic disorder associated with tissue injury. The condition is characterized by periodic or constant “pin-and-needle” sensations; stabbing, burning, or electric-shock-like pains; or feelings of tingling or numbness. Current medications have adverse side effects such as addiction and fatigue and only rarely alleviate pain completely.

Biochemist Gary J. Patti of Washington University in St. Louis; therapeutics expert Marianne Manchester of the University of California, San Diego; metabolomics specialist Gary Siuzdak of Scripps Research Institute; and coworkers detected the DMS surge via systematic metabolite analysis, known as metabolomics. They used liquid chromatography/mass spectrometry to survey metabolites in tissues from rats experiencing pain from a cut nerve. They found that DMS is produced at abnormally high levels in the rats’ spinal cords and causes pain when injected. The results suggest that inhibition of endogenous DMS production, with a methyltransferase or ceramidase inhibitor, for example, may be an attractive therapy, the researchers write.

“In this groundbreaking study, the authors have used metabolomics not only to provide new insights into the pathogenesis of chronic pain, but also to uncover a potential new therapeutic target for a condition that is extremely difficult to treat,” comments cellular stress response specialist Albert Fornace Jr. of Georgetown University.

“This is an exciting discovery,” says metabolite profiling expert Alan Saghatelian of Harvard University. If future studies confirm that DMS is involved in a new and unique pain pathway, “it will be a very important finding,” he says.

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Duncan Jefferson (January 23, 2012 10:58 AM)
Would you consider that the neuropathic pain found as a complication of Diabetes could be associated with a similar pathway, or is DMS just associated with tissue damage?
Duncan Jefferson
lLorenz K. Hinterauer (January 24, 2012 1:58 AM)
DMS-blood maybe urintest at a reasonable price is crucial from the clinical point of view.
Iurii Gubskyi (January 29, 2012 10:54 AM)
The investigation of Dr. Garry J.Patti and his colleagues is really an excellent break-through in understanding of the cellular and biochemical mechanisms of neuropatic pain development which is the most severe suffering in the vast number of people, primarily oncology patients.
Iurii Gubskyi. Professor of Biochemical Pharmacology. Kyiv, Ukraine.
Robert Zipkin (February 4, 2012 4:20 PM)
Contrary to this article's statment that "the overproduction of a previously unknown endogenous metabolite called N,N-dimethylsphingosine (DMS)....", DMS has been known for decades to be endogenous. see for example: Igarashi et al. J Biol CHem 1990 265:5385 and Igarashi et al BBRC 1989 164:1411

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