BALTIMORE — Lower back pain is an almost universal part of the human condition. At some point or another, we’ve all experienced an unpleasant painful sensation radiating from our lower back. Sometimes lower back pain is caused by strain or injury, but in a large percentage of cases, especially among older people, there is no apparent reason for the reported back pain. Now, researchers from Johns Hopkins Medicine have a new explanation: the cartilaginous tissue in our spines may be growing harder over time, developing into structures that resemble diffuse bone with a Swiss cheese-like structure. The openings in these structures then allow excessive pain-sensing nerves to enter the tissue, causing lower back pain.
The research team came to their conclusions by analyzing and experimenting with genetically engineered and old mice. They are hopeful that their discoveries can one day be used to develop treatments that stop abnormal nerve growth in the spine and subsequent lower back pain.
The spine is a series of joints, each made up of a bony vertebrae, a spinal disc, and a layer of soft tissue referred to as cartilage endplates. These endplates cushion the vertebral bones and protect them from the weight of the body.
“The cartilage endplate is the cushion on a seat that makes it more comfortable. But, like similar tissue in knee and hip joints, it succumbs to wear and tear over time,” says Xu Cao, Ph.D., Lee Riley Professor of Orthopaedic Surgery and researcher in the Johns Hopkins Institute for Cell Engineering, in a release.
According to Cao, researchers have long theorized that over time, the tissues in the spinal column change and deteriorate. This makes that area “fertile ground” for abnormal nerve growth, which would explain why the normal load-bearing work of the spine often becomes more painful as one ages.
In an effort to investigate this hypothesis, the research team examined the bony end plates of vertebrae collected from mice aged 20 months or more. In mouse years, that would mean they were around 70-80 years old by human aging standards.
The research team discovered that the soft, cartilaginous tissue in the mice’s spines had become hardened, resembling a bone filled with holes, just like Swiss cheese.
“Cartilage does not typically have nerve and blood vessels. However, when cartilage becomes a porous bony structure with growth of nerve fibers, it could be the source of back pain,” Cao says.
Prior research performed by the study’s authors had found similar results; that an aging or unstable spine can cause cartilage endplates to morph into hole-ridden bony structures that would certainly provide adequate space for nerves to enter. Moreover, a specialized cell type, called osteoclasts are known to cause these bone structures filled with holes where cartilage should be. With this knowledge, researchers hypothesized that the signaling molecule netrin-1, which is secreted by osteoclasts while morphing the cartilage, may actively invite abnormal nerve growth.
To test this theory, they examined spine tissue samples from old mice under a microscope, and labeled all observable osteoclasts and nerve fibers with tags. Sure enough, osteoclasts and nerve fibers were always present in the same areas, suggesting their hypothesis may very well be accurate.
Then, researchers wanted to see what would happen if they took osteoclasts completely out of the equation. This was accomplished by genetically engineering mice that were incapable of forming osteoclast cells and then manually destabilizing their vertebrae joints, essentially recreating the lower body instability seen in people dealing with lower back pain.
As expected, the mice with no osteoclast cells developed far fewer pain-sensing nerves in their vertebrae endplates in comparison to other mice.
The research team say their findings represent a major step forward in understanding and treating lower back pain. Moving forward, Cao and his team plan on conducting further experiments using substances that slow the development of abnormal bone structures.
The study is published in Nature Communications.