Researchers at the John Hopkins University School of Medicine say they have added to the evidence that age-related changes in spinal cartilage tissue could cause excessive growth of painful nerves that cause lower back pain.
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The team hopes that their findings from experiments with genetically modified mice can one day help researchers develop treatments that target abnormal nerve growth in the spine, preventing lower back pain.
Low back pain a common problem
Low back pain is an almost universal problem, affecting approximately 80% of people worldwide at some time in their lives. In some cases, pain is the result of a 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 back pain is nonspecific and has no apparent patho-anatomic cause.”
Age-related cartilage changes could be the source of pain.
Now, Xu Cao of the Department of Orthopedic Surgery of John Hopkins and his colleagues suggest an explanation. The findings of his study suggest that as cartilaginous spinal tissue hardens with age, it develops porous structures similar to Swiss cheese that allow pain-sensitive nerves to grow in the tissue, which triggers lower back pain.
The cartilage does not usually have nerves and blood vessels. However, when the cartilage becomes a porous bone structure with the growth of nerve fibers, it could be the source of back pain. “
The spine can be described as a series of joints, each consisting of bone vertebrae, a spinal disc and soft tissue layers called cartilage end plates that protect the vertebrae from spinal load work.
“The cartilage end plate is the cushion in a seat that makes it more comfortable. But, like a similar tissue in the knee and hip joints, it succumbs over time,” explains Cao.
The team’s experiments were designed to assess whether sensory nerves that grow on the cartilaginous end plates of the spine could cause lower back pain that is commonly reported in the absence of any injury or tension. Cao says researchers have long theorized that age-related changes and deterioration of tissue in the spine provide “fertile ground” for the excessive growth of these sensory nerves, which could explain why the regular actions of Spinal load become more painful as people get older.
What did the study consist of?
As reported in the magazine Nature Communications, the researchers examined the end plates of cartilage vertebrae in mice older than 20 months, the equivalent of approximately 70 to 80 years in humans.
The team discovered that the end plates had hardened, filling with holes, resembling diffuse bones with a structure similar to a Swiss cheese.
Previous studies by the team had reported that an aged spine can cause cartilage end plates to become porous bone structures that would provide holes for nerves to enter. Specialized cells called osteoclasts, which dissolve and absorb bones, create these holes in the areas where the cartilage should be. As it is known that osteoclasts secrete the Netrin-1 signaling molecule during this process of cartilage change, Cao thought that perhaps this molecule actively invites abnormal nerve growth and, in turn, causes back pain.
To test this hypothesis, the researchers microscopically examined spinal tissue samples taken from old mice and labeled all visible osteoclasts and nerve fibers with fluorescent labels.
They discovered that osteoclasts and nerve fibers coexisted in the same parts of the vertebrae, suggesting that osteoclasts could somehow be inducing nerve growth, possibly through netrin-1.
Then, the team genetically designed knock-out mice that lack the gene that encodes osteoclasts, to test what would happen without their hole formation and netrin secretion capabilities.
After surgically destabilizing the joints between the vertebrae of the mice to mimic the instability observed in human low back pain, the team discovered that mice without osteoclasts had significantly less pain-sensitive nerves in their endplates, compared to mice that had osteoclasts
An important advantage for possible therapeutic objectives
Cao says the results show that the porous structure of cartilaginous end plates is an important step forward in understanding how unexplained lower back pain develops and an important step towards the development of new treatments.
“These findings suggest that porosity of the osteoclast-initiated endplates and sensory innervation are potential therapeutic targets for spinal pain,” the team concludes.
Next, the researchers plan to use compounds known to delay the development of abnormal bone structures to assess 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
A study says that Swiss cheese bones can explain low back pain 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 end plates by Netrin-1 osteoclasts mediates spinal hypersensitivity induced by PGE2 in mice. Nature Communications 10, Article number: 5643 (2019) Available at https://www.nature.com/articles/s41467-019-13476-9