UK Biobank participants’ genetic data and questionnaire answers reveal some of the biological underpinnings of pain – raising hope of new therapies for the billions of people who experience persistent pain.
Summary
Genetic information from more than 1.5 million people, including UK Biobank participants, has revealed a gene that predisposes people to chronic pain. It could be a pivotal discovery for researchers developing new painkillers since current chronic-pain treatments are ineffective or even dangerous.
A gene that predisposes people to chronic pain was found by researchers digging through genetic information from more than 1.5 million people, including UK Biobank participants. The discovery could be “a pivotal moment” for developing treatments for persistent pain – a condition for which no effective therapies exist.
When pain becomes chronic
Chronic pain affects one in five people, particularly older people and women.
Pain becomes chronic when it lasts longer than about three months. It affects one in five people, particularly older people and women. Despite how common it is, there’s surprisingly little known about what causes chronic pain, on a biological level. In some cases, it’s a disease such as arthritis; in other cases, there’s no obvious underlying condition.
What is clear is that chronic pain works differently to the acute pain we feel, for example, when we cut a finger or twist an ankle. “One of the main things we think that changes if you experience chronic pain is that your nervous system becomes ‘hyped up’,” explains neuroscientist Franziska Denk from King’s College London, UK, who works independently of the study team. “[Your brain] gets a little bit anxious and stressed out, and keeps seeing pain where maybe there wouldn’t need to be so much pain.”
We definitely need new treatments. And if we’re ever going to do that, we need to understand the mechanisms of [chronic pain] and find new molecular targets.
Professor David Bennett, University of Oxford, UK
Painkillers tend to be ineffective or even dangerous for chronic pain. Opioids, for example, are powerful against acute pain but can lead to serious addiction when taken long term.
“We definitely need new treatments,” says study co-leader David Bennett from the University of Oxford, UK. “And if we’re ever going to do that, we need to understand the mechanisms of [chronic pain] and find new molecular targets.”
A door to our bodies’ cells
Bennett’s team dug into UK Biobank participants’ genetic data and their responses to a pain questionnaire. This revealed how some versions of one particular gene predisposed people to more severe levels of chronic pain. The team found the same genetic link in participants of the Finnish Genetics project and the US-based Million Veteran Program.
Bennett worked with study co-leader Simon Newstead’s team to figure out that the gene contained instructions for a ‘transporter protein’ that was particularly common in some nerve cells. Transporter proteins act like doors between the inside and the outside of our bodies’ cells. Their function influences how pain is perceived and processed.
Other genes for other transporter proteins have been linked to chronic pain before. It’s likely that many different genes play a role in chronic pain, and that inherited factors are part of the reason why the condition affects women more than men.
To do human genetics at scale, you need hundreds of thousands of people engaging in research. We wouldn’t have made this discovery without [UK Biobank participants].
Professor David Bennett, University of Oxford, UK
“The key new thing about this study is exactly understanding what this gene does,” says Denk. “Based on that, now we can really start looking at why this is playing a role in the pain pathway and how we can harness this for drug development.”
Scientists working on new painkillers will likely be very interested in exploring this transporter’s function, Denk adds. “I think it could be quite a pivotal moment.”
Bennett highlights how grateful he is to the UK Biobank participants who donated their time attending assessments and filling out the online pain questionnaires. “To do human genetics at scale, you need hundreds of thousands of people engaging in research,” he says. “We wouldn’t have made this discovery without them.”
Related publication
- Nature, August 2025
