Understanding Chronic Pain

(Ivanhoe Newswire) -- Millions of people worldwide suffer from a type of chronic pain called neuropathic pain, which is triggered by nerve damage. Exactly how this pain persists is still unknown, and treatment has been largely ineffective. But a new research is helping doctors understand the pain and fix it!

It’s critical and it affects thousands every year, but Gary J. Patti, assistant professor of genetics, chemistry, and medicine at Washington University in St. Louis and research associate at Scripps Research, and a team of scientists, are using a new approach, known as metabolomics, to help in the discovery of identifying new clues to understanding chronic pain.

Metabolomics, by contrast, concerns differences in the levels of small-molecule metabolites, such as sugars, vitamins, and amino acids, that serve as the building blocks of basic cellular processes. It is increasingly used to find biochemical markers or signatures of diseases. "The idea was to apply metabolomic analysis to understand the biochemical basis of the neuropathic pain condition and reveal potential therapeutic targets," Gary Siuzdak, a senior investigator in the study, and professor of chemistry and molecular biology and director of the Scripps Research Center for Metabolomics, was quoted saying. "We call this approach 'therapeutic metabolomics'."

The scientists began with a standard model of neuropathic pain in lab rats. Patti, Siuzdak, and their colleagues sampled segments of a previously injured tibial leg nerve triggering neuropathic pain, as well as the rats' blood plasma and tissue from the rats' spinal cords. The scientists then determined the levels of metabolites in these tissues, and compared them to levels from control animals.

To their surprise, the researchers found that nearly all the major abnormalities in metabolite levels were present not in the injured leg nerve fiber, nor in blood plasma, but in tissue from the "dorsal horn" region of the spinal cord which normally receives signals from the tibial nerve and relays them to the brain. After discovering this fact, the researchers set up a test to see which of the abnormally altered metabolites in dorsal horn tissue could evoke signs of pain signaling in cultures of rat spinal cord tissue. One metabolite stood out. Dimethylsphingosine (DMS) is a small-molecule byproduct of cellular membranes in the nervous system.

The scientists also found that DMS is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected. These findings suggest that inhibiting this molecule may be a fruitful target for drug development.

"We think that this is a big step forward in understanding and treating neuropathic pain, and also a solid demonstration of the power of metabolomics," Patti said.

SOURCE: Scripps Research Institute, January, 2012