Researchers at the John Hopkins University School of Medicine say they have added to the evidence that age-related changes to spinal cartilage tissue could invite painful nerve overgrowth that causes lower back pain.
Image Credit: Sebastian Kaulitzki/Shutterstock.com
The team is hopeful that their findings from experiments with genetically engineered mice, may one day help researchers develop treatments that target abnormal nerve growth in the spine, preventing lower back pain.
Lower back pain a common problem
Lower back pain is an almost universal problem, affecting an estimated 80% of people worldwide at some point in their lives. In some cases, the pain is the result of strain or injury, but for the vast majority of people, and particularly older people, there is no apparent explanation for the pain.
The researchers say that “in total, 90% of lower back pain is nonspecific and has no apparent pathoanatomical cause.”
Age-related changes in cartilage could be the source of pain
Now, Xu Cao from the John Hopkins Department of Orthopaedic Surgery and colleagues suggest an explanation. Their study findings suggest that as the cartilaginous spinal tissue hardens with age, it develops swiss cheese-like, porous structures that allow pain-sensing nerves to grow into the tissue, triggering lower back pain.
Cartilage does not typically have nerve and blood vessels. However, when cartilage becomes a porous bony structure with the growth of nerve fibers, it could be the source of back pain,”
The spinal column can be described as a series of joints, each made up of bony vertebrae, a spinal disc and soft-tissue layers called cartilage endplates that protect the vertebrae from the weight-bearing work of the spine.
"The cartilage endplate is the cushion on a seat that makes it more comfortable. But, like similar tissue in the knee and hip joints, it succumbs to wear and tear over time," explains Cao.
The team’s experiments were designed to test whether sensory nerves growing into the cartilaginous endplates of the spine could cause the lower back pain that commonly gets reported in the absence of any injury or strain. Cao says researchers have long theorized that age-related changes and deterioration of the tissue in the spinal column provide “fertile ground” for overgrowth of these sensory nerves, which might explain why regular load-bearing actions of the spine become more painful as people age.
What did the study involve?
As reported in the journal Nature Communications, the researchers examined the cartilage endplates of vertebrae in mice older than 20 months – the equivalent of about 70 to 80 years in humans.
The team found that the endplates had hardened, becoming filled with holes, resembling diffuse bone with a Swiss cheese-like structure.
Previous studies by the team had reported that an aging spine can cause cartilage endplates to turn into porous bony structures that would provide holes for nerves to enter. Specialized cells called osteoclasts, which dissolve and absorb bone, create these holes in areas where the cartilage should be. Since osteoclasts are known to secrete the signaling molecule Netrin-1 during this cartilage-changing process, Cao thought that perhaps this molecule actively invites abnormal nerve growth and, in turn, leads to back pain.
To test this hypothesis, the researchers microscopically examined spine tissue samples taken from old mice and labeled all visible osteoclasts and nerve fibers with fluorescent tags.
They found that osteoclasts and nerve fibers co-existed in the same parts of the vertebrae, suggesting that the osteoclasts could somehow be inducing the nerve growth, possibly via netrin-1.
Next, the team genetically engineered knock-out mice lacking the gene that codes for osteoclasts, to test what would happen without their hole-forming and netrin1-secreting abilities.
After surgically destabilizing the joints between the mice’s vertebrae to mimic the instability seen in human lower back pain, the team found that mice without osteoclasts had significantly fewer pain-sensing nerves in their endplates, compared with mice that did have osteoclasts.
An important lead for potential therapeutic targets
Cao says the findings show that the porous structure of cartilaginous endplates is an important lead in understanding how unexplained lower back pain develops and a major step towards developing new treatments.
“These findings suggest that osteoclast-initiated porosity of endplates and sensory innervation are potential therapeutic targets for spinal pain,” concludes the team.
Next, the researchers plan to use compounds known to slow the development of abnormal bone structures to test whether they relieve lower back pain.
Swiss cheese bones could be the cause of unexplained low back pain. Medical Express 2010. Available at: https://medicalxpress.com/news/2020-01-swiss-cheese-bones-unexplained-pain.html
Swiss Cheese Bones’ May Explain Lower Back Pain, Study Says. Study Finds 2020. John Anderer. Available at: https://www.studyfinds.org/swiss-cheese-bones-may-explain-lower-back-pain-study-says/
Cao X, et al. Sensory innervation in porous endplates by Netrin-1 from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice. Nature Communications 10, Article number: 5643 (2019) Available at https://www.nature.com/articles/s41467-019-13476-9