Oxford Scientists Identify New Genetic Target for Chronic Pain Treatment
By Viola Spada
A groundbreaking study published in Nature by Oxford University researchers has uncovered a new genetic link to chronic pain: a finding that could transform how doctors treat one of the world’s most disabling conditions.
Chronic pain affects millions globally, often persisting long after injuries heal and severely diminishing quality of life. Current treatments, including opioids, can relieve pain but carry major risks such as addiction and tolerance. For decades, scientists have sought to uncover the precise biological mechanisms behind chronic pain, but the puzzle remained unsolved, until now.
In a collaboration between the Nuffield Department of Clinical Neurosciences (NDCN) and the Oxford Department of Biochemistry, Professors David Bennett and Simon Newstead led a team that identified a gene, SLC45A4, strongly linked to pain perception. This discovery not only clarifies how certain nerve cells become overactive but also pinpoints a new potential drug target.
The Oxford team began by analysing genetic and health data from the UK Biobank, comparing gene variants with self-reported pain levels from thousands of participants. They found that individuals with a specific variant of SLC45A4 consistently reported higher pain levels. Dr Steven Middleton, lead author of the paper, explained: “Linking SLC45A4 to chronic pain in humans was really exciting, but the next challenge was unravelling exactly what it does in the body.” Professor Newstead’s group determined the 3D atomic structure of the protein encoded by SLC45A4. They discovered that it acts as a polyamine transporter, a long-sought molecule responsible for moving polyamines across nerve cell membranes.
Polyamines help regulate how neurons respond to stimuli. In chronic pain conditions, nerve cells (called nociceptors) can become oversensitised, sending too many pain signals to the brain. High levels of polyamines are thought to contribute to this overactivity. By identifying the specific transporter that controls polyamine movement, the Oxford team revealed a precise molecular mechanism that could be targeted to “dial down” pain sensitivity.
Professor Bennett emphasised the importance of these findings: “Chronic pain remains a huge societal problem as it becomes more common and current treatments fail. We need to understand the mechanisms behind pain and, importantly, identify new targets for treatment.” If future research confirms that drugs can safely inhibit this transporter in humans, it could lead to a new generation of painkillers that work directly on nerve sensitivity, without the side effects and dependency risks of opioids.
This discovery marks a milestone in neuroscience, showing how modern genetics, biochemistry, and imaging technologies can work together to solve complex medical problems. While clinical applications are still years away, the identification of SLC45A4 as a pain-regulating gene offers real hope for millions living with chronic pain. As Professor Bennett concluded: “We discovered a new pain gene, gained insights into its atomic structure, and connected its function to how neurons respond to injury. Ultimately, our findings reveal a promising new target for treating chronic pain.”
