Key molecule to detect and treat chronic pain discovered

By Biocat

A study published in the journal Nature Chemical Biology opens the doors to detecting and treating chronic pain. A group of scientists from the Scripps Research Institute (San Diego, USA), which includes Dr. Òscar Yanes, have discovered that dimethylsphingosine (DMS) is one of the keys to persistent pain. DMS is a small molecule that accumulates in the spinal cord of rats suffering from neuropathic pain and is triggered by nerve damage. DMS also causes pain when injected into rats that previously had none.

Òscar Yanes holds a PhD in Biochemistry from the Autonomous University of Barcelona (UAB). After four years of post-doctoral work as a research associate at the Scripps Research Institute, he returned to Catalonia last year to work at the URV because they have a metabolomics platform that has allowed him to continue developing this project as a researcher at Rovira i Virgili University (URV) and the Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (Ciberdem). Yanes is the first co-author of the article and the researcher who initiated the study, took samples, carried out the comparative analyses and discovered DMS. At the URV, Yanes leads his own group (www.yaneslab.com).

During the study, scientists measured metabolites in blood, spinal cord and nerves, “and we found that in the spinal cord, just where it connects with the nerve that transmits information to the brain, there were great differences between the rats that had pain and those that didn’t,” explained Dr. Òscar Yanes. From this point, they discovered that the metabolites triggered by nerve damage accumulated in the spinal cord, specifically in a small part that receives the signals the sciatic nerve transmits to the brain.

These compounds are associated with a metabolic pathway, and this pathway contains enzymes, which are the proteins that transform these small molecules. “We have shown that there is a metabolic pathway into which we can intervene, as we have shown a chain reaction that in the future can be useful in finding inhibitors.” Yanes points out that, if it were possible to block the enzymes that end up generating DMS, we could reduce pain. Although we must show that the model can be extrapolated to all types of chronic pain, we previously knew almost nothing about this disease on a molecular level “and this is a good first step.”

According to Dr. Yanes, this work can move towards researching pain associated with diabetes, which is what he is studying at the URV metabolomics platform and at the Ciberdem: “First we must see if the results can be extrapolated to humans. We also need to know if DMS accumulates in humans suffering from chronic pain, or find a model mouse with diabetes on which to carry out research similar to what we have been doing so far.”

The idea is to look for these compounds in the blood of patients with chronic pain: “We can find markers, try to quantify the pain and provide tools for clinics so that patients don’t have to quantify their pain with a test.” And another focus of the study is to discover where the pain comes from: “Knowing the metabolic pathway and the compounds that accumulate there, in the short term we must look for them in blood or cerebrospinal fluid, which is a simpler strategy for developing drugs.”

This breakthrough has been possible thanks to mass spectrometry techniques used in metabolomics, a new field of science that is increasingly used to find biochemical markers and indicators of disease.