In experiments with genetically engineered and old mice, researchers from the Institute for cell engineering at Johns Hopkins say that the vast majority of back pain in people can be due to excessive growth of pain nerves in the spinal cartilaginous tissue.
It is estimated that 80% of people worldwide will experience back pain during their life, sometimes due to stress or injury. But the vast majority of lower back pain, the researchers say, occurs in the absence of injury, especially in the elderly.
New experiments were designed to study whether painful growth of sensory nerves in the cartilaginous end plates of the spine be the root of these unexplained cases.
Cartilage usually do not have nerves and blood vessels. However, when cartilage becomes porous bone structure with the growth of nerve fibers, it can be a source of back pain.
The results, published December 10, 2019 in the journal Nature Communications, may eventually help develop new treatments that target abnormal growth of nerves in the spine.
The spine can be described as a series of joints, each of which consists of the bone of the vertebrae, vertebral disc and a layer of soft tissue called cartilage end plates that soften vertebral bones to protect them from the weight of the body.
“End plate cartilage is a cushion on the seat, which makes it more convenient. But like similar fabric at the knee and hip joints, it is susceptible to wear and tear over time,” says Xu Cao, Ph. D., Professor of orthopaedic surgery and research fellow, Institute of cell engineering Johns Hopkins Medical school at Johns Hopkins University.
Tsao says he and his team have long suspected that age-related changes in the tissues that make up the spine, provide fertile ground for abnormal growth of nerves, which makes the normal work of the bearing of the spine painful.
To explore this idea, Cao and his team analyzed samples of bone end plates of the vertebrae from mice aged more than 20 months, the equivalent age of a human is 70-80 years. The researchers found that the soft cartilage in the spine of mice hardened and resembled diffuse bone structure, like Swiss cheese.
In previous studies, the team, Cao said that aging or unstable spine causes the end plates of cartilage change in porous bone structures, which provide space for the nerves to penetrate the dense bone structure. Specialized type of cells called osteoclasts, creates a porous bone structure where there should be cartilage. Cao thought, perhaps signaling molecule netrin-1 secreted by osteoclasts during the process, causing abnormal growth of nerves and the resulting pain in the back.
“Cartilage usually do not have nerves and blood vessels. However, when cartilage becomes porous bone structure with the growth of nerve fibers, it can be a source of back pain”, says Professor Cao.
To test this idea further, Cao and his colleagues first analyzed the tissue samples of older mice under the microscope, marking derobrachus osteoclasts and nerve fibers labeled with fluorescent labels. They found that osteoclasts and nerve fibers were present in the same areas of the vertebrae, suggesting that osteoclasts could somehow signal the growth of a nerve, perhaps with the help netrin-1.
The team then devised an experiment to prevent the osteoclasts from the production of abnormal growth of bones Swiss cheese and allocation netrin-1 to see whether it is possible to stop the growth of nerves in the cartilage — and pain involved.
They genetically engineered mice so they lacked the gene that encodes the formation of osteoclasts, and performed surgery on the mice to destabilize the joints between their vertebrae, mimicking a similar instability observed in people with low back pain. The researchers found that mice that lacked the cells of osteoclasts, had less pain medication nerves in their end plates of the vertebrae than mice with the gene.
The researchers claim that the results of the experiments confirmed the porous structure of the cartilage endplates is an important guide in understanding the development of unexplained pain in the lower back. The team next plans to conduct laboratory experiments using compounds that slow the abnormal bone growth, to test their potential for the treatment of back pain.