Researchers Find Molecular Clue to Understanding Neuropathic Pain

Scientists from The Scripps Research Institute found dimethylsphingosine, a small-molecule byproduct of cellular membranes in the nervous system, is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected, according to an institute news release.

While the known cause of neuropathic pain is nerve damage, the exact reason the pain persists is unknown. Using a new approach called metabolomics, which looks at differences in the levels of small-molecule metabolites that serve as the foundation of basic cellular processes, researchers determined the levels of metabolites in tissue from previously injured tibial leg nerves in rats.

Researchers found that all the major abnormalities in metabolite levels were present in the dorsal horn region of the spinal cord, not the injured leg nerve fiber or in blood plasma as expected. The dorsal horn region receives signals from the tibial nerve and sends them to the brain. The molecule DMS, a byproduct of cellular reactions involving sphingomyelin, a molecule in the insulating sheaths of nerve fibers, stood out to researchers. They also determined DMS causes pain by stimulating the release of pro-inflammatory molecules from astrocytes, neuron-supporting cells.

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