Neck and back pain could be caused by changes in gene activity that trigger the breakdown of the spine's natural shock absorbers, new research suggests.
Findings from a study in zebrafish suggest that changes in gene activity can lead to a build-up of minerals in the spine – similar to unwanted bone forming in the wrong place – causing it to harden.
Experts say the findings point to potential future drug targets to treat back pain and suggest zebrafish could be a valuable tool for testing them.
Back pain affects most people at some point in their lives. One of the main underlying causes is the gradual breakdown of spinal discs – which cushion the bones of the spine – known as intervertebral disc degeneration (IVDD).
Despite how common and costly IVDD is, there are currently no drugs that can stop or reverse the condition. Surgery remains the only long-term option.
Genetics are known to play a role in the development of IVDD. A gene connected to a protein called collagen IX – which helps hold the disc's structural fibres together – has been repeatedly linked to early-onset disc problems.
Scientists from the Universities of Edinburgh and Bristol studied zebrafish that were bred to lack a working copy of the gene to better understand how genetic faults could lead to disc disease.
As the fish aged, their spines developed problems strikingly similar to human disc disease. The bones of the spine fused together and the tissue between vertebrae became abnormally hardened with mineral deposits.
The team found that this hardening was preceded by a breakdown in a supportive scaffold layer in the developing spine, well before any mineral began to build up.
Researchers looked at which genes were switched on or off in the fish. They uncovered disruptions to how the body handles fat and to a growth-control pathway called mTOR, alongside changes in phosphate handling and vitamin A signalling – all processes linked to mineral buildup.
Excitingly, they were also able to demonstrate ways to reduce the damage. A bone-protecting drug already used for osteoporosis – known as a bisphosphonate – blocked the mineral buildup. Simply restricting the fish's food intake, or using drugs that dampen fat metabolism, also reduced spinal fusions.
The findings point to phosphate handling and fat metabolism as promising targets for future drugs, experts say.
The study, supported by Arthritis UK and BBSRC, is published in the journal Communications Biology: https://www.nature.com/articles/s42003-026-10702-1 .
Study lead, Dr Erika Kague, from the University of Edinburgh's Institute of Genetics and Cancer, said: "For decades, surgery has been the only real answer for disc disease. By understanding the biology that drives the spine to harden, our zebrafish studies point to several ways of slowing it down, including a drug already used safely in patients. There's more work to do, but for a condition that's affected people for generations without a treatment in sight, this is super exciting."
Dr Caroline Aylott, Head of Research Delivery at Arthritis UK, said: "For the 9.5 million people across the UK living with back pain this research brings fresh hope that potential new therapeutic approaches are on the horizon.
"We are proud to fund research that is unlocking the science behind the processes leading to spinal disc degeneration. Back pain is one of the UK's most common conditions that has blighted millions over generations. Dr Erika Kague and her team at the University of Edinburgh have uncovered important genetic evidence that could pave the way for new treatments, bringing us one step closer to a future where fewer people have to live with the daily pain and challenges that back pain can bring."
Dr Jef Grainger, Executive Director – Bioscience Advancing Knowledge at BBSRC, said: "This research shows how publicly funded discovery bioscience can generate the knowledge needed to address major health challenges. By revealing new knowledge of how healthy biological processes break down in ageing-related spinal disc degeneration, the study opens up promising avenues for future treatment development. It's a great example of how BBSRC-supported research helps turn scientific discovery into knowledge and innovations that have the potential to improve people's lives."
