SLC8A3

Researchers at Oxford University have identified a gene linked to pain, opening possibilities to develop drugs or gene therapies to help treat patients who suffer from chronic pain. In a two-part study, researchers from Oxford's Nuffield Department of Clinical Neurosciences compared genetic variation in samples from more than 1,000 participants. The study’s purpose was to see if there were genetic differences among patients who experienced “pain wind-up.” Pain wind-up is a phenomenon where repeated stimulation, such as with a sharp pin prick, can lead to a heightened sensitivity to pain. Higher pain wind-up contributes to clinical pain disorders. David Bennett, Ph.D., professor of neurology and neurobiology at the Nuffield Department of Clinical Neuroscience, said the study was performed in Colombia, a location chosen for its racial and ethnic diversity. “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,” Bennett said. After completing the first part of the Oxford study, which involved a genetically diverse human population base, scientists noted a significant difference in variants of one specific gene: a protein sodium-calcium exchanger type-3 called NCX3. The second part of the study was a series of experiments on mice. The goal of these studies was to understand how NCX3 regulates pain wind-up and whether it may be a treatment target. Researchers learned NCX3 was expressed in the mouse spinal cord neurons that process and transmit pain signals to the brain. Low levels of NCX3 were associated with pain wind-up, faster exportation of calcium by NXC3 proteins and more activity in response to injury signals. However, higher levels of NCX3 within the spinal cord could reduce pain in the mouse. "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,” Bennett told Medical Xpress. "The findings imply that any drugs which can increase activity of NCX3 would be predicted to reduce pain sensitization in humans." The U.S. Centers for Disease Control and Prevention reports about 20% of adults in the United States suffer from some type of chronic pain, and chronic pain is more prevalent among underserved populations such as women, older adults and people living in poverty. Despite the prevalence of chronic pain, scientists do not always understand what causes it or why it seems to occur more frequently in certain populations. Often, chronic pain is treated with painkillers like opioids. However, because of the potential for addiction and abuse, Mayo Clinic’s website advises that “If you're living with chronic pain, opioids are not likely to be a safe and effective long-term treatment option…. Aim for a treatment plan that makes it possible to enjoy your life without opioids, if possible.” If Oxford researchers can use this information to develop a drug or a gene therapy treatment to treat chronic pain, it would be a lucrative product. According to a report by Transparency Market Research, the global pain management therapeutics market is expected to hit $92,123.4 million by 2027.