Pain Regulation Gene Discovery Leads to New Treatment Target

Researchers at the University of Oxford in the United Kingdom have discovered a gene that is involved in chronic pain, which has not only enabled them to understand an important mechanism of this issue in humans but has also created a new treatment target.

According to a June 15, 2022 press release, the researchers from the university’s Nuffield Department of Clinical Neurosciences performed a two-part study involving both people and mice. Initially, the researchers compared genetic variation in human samples from more than 1000 participants from Columbia.

More specifically, the scientists looked at whether there were any common genetic variants in people who experience a heightened sensitivity to pain (pain wind-up). From the analysis of the samples, the researchers found that there was a significant difference in variants of the protein Sodium Calcium exchanger type-3, NCX-3, in people who experience greater pain wind-up.

After the researchers had made these assessments, they then performed a series of experiments in mice to understand how NCX3 regulates pain wind-up. In the second part of their study, the researchers found that NCX3, which was expressed in the spinal cord neurons of the mice that process and transmit pain signals to the brain, was needed to transport excess calcium. When there was no NCX3, the neurons in the spinal cord were more active when the mice suffered an injury and the pain wind-up was greater. However, when the levels of NCX3 were increased, the amount of pain in the mouse was lower.

“This is the first time that we have been able to study pain in humans and then to directly demonstrate the mechanism behind it in mice, which provides us with a really broad understanding of the factors involved and how we can begin developing new treatments for it,” said David Bennett, professor of Neurology and Neurobiology, Nuffield Department of Clinical Neuroscience, in the press release. “Chronic pain is a global problem, and can be immensely debilitating. We carried out the study in Colombia because of the mixed ancestry of the population there, including Native Indian, African, and European populations, which gave us a broad range of genetic diversity to look at. This makes these findings so exciting because of their potential international applications. The findings imply that any drugs which can increase activity of NCX3 would be predicted to reduce pain sensitisation in humans.”

Source: University of Oxford