Changes in gene activity may contribute to neck and back pain by damaging the discs that act as the spine’s natural shock absorbers, according to new research.
A study using zebrafish found that altered gene activity can cause minerals to accumulate within the spine. This process resembles bone forming where it should not, eventually making spinal tissue unusually hard.
Researchers say the results reveal several biological processes that could become targets for future back pain treatments. The work also indicates that zebrafish may provide a useful model for testing potential therapies.
Why Spinal Discs Break Down
Most people experience back pain at some point. A major cause is the progressive deterioration of the discs that cushion the bones of the spine, a condition called intervertebral disc degeneration (IVDD).
Although IVDD is widespread and places a considerable burden on patients and health care systems, no medications can currently halt or reverse its progression. Surgery is still the only available long-term treatment.
Inherited factors are known to influence a person’s risk of developing IVDD. Previous research has repeatedly connected early disc problems to a gene associated with collagen IX, a protein that helps bind together the structural fibers inside spinal discs.
To investigate how defects in this gene might cause disc disease, researchers from the Universities of Edinburgh and Bristol studied zebrafish bred without a functioning copy of it.
Zebrafish Developed Human-Like Spinal Damage
As the zebrafish grew older, they developed spinal abnormalities that closely resembled disc disease in people. Their vertebrae fused, while mineral deposits caused the tissue between the bones to become abnormally hard.
The researchers discovered that this mineralization did not begin immediately. First, a supportive scaffold layer within the developing spine started to deteriorate. Mineral deposits appeared only after this early structural damage had occurred.
The team then examined patterns of gene activity in the fish to determine which genes had become more or less active.
Their analysis revealed problems with fat processing and with mTOR, a pathway that regulates growth. They also found changes involving phosphate control and vitamin A signaling. Each of these processes has been associated with abnormal mineral accumulation.
Existing Osteoporosis Drug Reduced Mineral Buildup
The researchers also identified several approaches that reduced the spinal damage.
A bisphosphonate, a type of bone-protecting medication already used to treat osteoporosis, prevented minerals from accumulating. Spinal fusion was also reduced when the fish received less food or were treated with drugs that suppressed fat metabolism.
According to the researchers, the results highlight phosphate regulation and fat metabolism as especially promising areas for the development of future medicines.
The study was funded by Arthritis UK and BBSRC and published in the journal Communications Biology.
New Possibilities Beyond Surgery
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 of 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 aging-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.”