Breakthrough discovery reveals new gene linked to chronic pain

A major scientific breakthrough has uncovered a new genetic link to chronic pain, offering hope for millions who suffer daily. For the first time, researchers have identified a new gene, SLC45A4, that plays a key role in how the body processes and feels pain. The discovery, published in Nature, opens the door to developing new, targeted treatments that could reduce the need for addictive opioids.

Professor Simon Newstead, David Phillips Chair of Molecular Biophysics in the Department of Biochemistry, University of Oxford said: 

"Significant discoveries occur when we grasp how the complex tissues and organs in our bodies function and communicate. Membrane transporters play a fundamental role in this communication. Our findings now reveal a new link between membrane transport and chronic pain, paving the way for a deeper understanding of how metabolism and pain are connected in the human body."

Chronic pain is one of the leading causes of disability worldwide, yet its underlying biological causes have remained a mystery — until now. In this study, funded by Wellcome and supported by the NIHR Oxford Health Biomedical Research Centre (OH BRC), researchers from the Department of Biochemistry, the Kavli Institute for Nanoscience Discovery, and the Nuffield Department of Clinical Neurosciences, University of Oxford, collaborated across diverse medical disciplines. Together, they combined genetic data with detailed imaging and functional studies to identify a new gene, SLC45A4, that controls pain sensitivity. The gene produces a transporter that moves natural chemicals called polyamines across nerve cells. These chemicals, when overly abundant, disrupt how nerve cells function — sending more pain signals to the brain than normal.

Cryo-Em structure of the SLC45A4 polyamine transporter (Illustration by Sigurbjörn Markússon at the Department of Biochemistry and the Kavli Institute of Nanoscience Discovery)

By studying mice lacking this gene, the Oxford neuroscience team, led by Professor David Bennett, found they were less sensitive to painful stimuli like heat or pressure. This suggests that targeting the gene or its transporter could be an effective way to reduce chronic pain.

The discovery marks the first time this specific transporter has been seen in 3D in humans, and researchers now plan to study how factors like diet or genetic variation affect its function. Eventually, this could lead to drugs that precisely block or adjust how SLC45A4 works — reducing pain at the source, without affecting the rest of the brain like opioids do.

Professor David Bennett, Head of the Division of Clinical Neurology and Professor of Neurology and Neurobiology at the University of Oxford, and OH BRC Pain Co-Theme Lead, said:

"We discovered a new pain gene, gained insights into the atomic structure of this molecule, and connected its function to the excitability of neurons that respond to tissue injury. Ultimately, our findings reveal a promising new target for the treatment of chronic pain."

This finding represents a promising step toward safer, smarter pain relief — and a potential turning point in how chronic pain is understood and treated. With further research, if a successful drug can be developed, it could reduce long-term, chronic pain without relying on strong opioids, leading to safer and more effective treatments for patients worldwide.

Lead author on the paper, senior post-doctoral researcher, Dr Steven Middleton explained: 

"Linking SLC45A4 to chronic pain in humans was really exciting, but the next challenge was unravelling exactly what SLC45A4 does in the body. Remarkably, we identified that SLC45A4 is the long-awaited neuronal polyamine transporter, which is particularly important in regulating how some nerves respond to painful stimuli. Our work exemplifies the power of discovery science and multi-disciplinary collaboration."

The full paper 'SLC45A4 is a pain gene encoding a neuronal polyamine transporter' is published in Nature.

Read the article ‘The hunt is on for non-addictive pain treatments – our research could help' on the Wellcome website.

You can also hear Professor David Bennett speaking about the research on BBC Radio 4 Today Programme (2:22)