An Existing Drug Could Provide the Answer to Treating Lower Back Pain
An existing drug that targets senescent, or sleeping cells could provide the answer to treating lower back pain, according to a new study.
The research advances our understanding of the role of senescent osteoclasts — cells that break down and remove damaged bone tissue — in the development of lower back pain, which affects 8 in 10 people at some point in their lives. Editors say the study provides compelling evidence that an existing drug, Navitoclax, can eliminate senescent osteoclasts in mice and, in doing so, markedly reduce spinal pain.
“It’s previously been shown that senescence promotes age-related musculoskeletal diseases such as osteoporosis, and removing senescent cells from degenerated vertebral discs restores the intervertebral disc structure,” explains lead author Dayu Pan. “We previously found that osteoclasts cause the endplates between each vertebra and disc to become porous, allowing infiltration of new nerves that cause lower back pain. In this study, we set out to test whether this is caused by a specific group of senescent osteoclasts and whether eliminating these osteoclasts could reduce the pain.”
The research team first set out to identify whether senescent osteoclasts were present in the porous endplates of vertebrae in mice with two types of spine hypersensitivity — one caused by aging and the other caused by lumbar spine instability. They tested for the simultaneous presence of two markers within the bone — ‘TRAP’ which is a hallmark of osteoclasts, and p16, used to identify senescent cells. In both types of spinal degeneration, they saw a strong association between the presence of senescent osteoclasts and the degree of degeneration and spine hypersensitivity.
Next, they explored whether a drug called Navitoclax, which targets senescent cells, could eliminate senescent osteoclasts and reduce spinal hypersensitivity. As hoped, the treatment caused a significant reduction in senescent osteoclasts compared to untreated mice, as well as reduced pain and increased activity in mice with both types of spine degeneration.
Spinal scans and microscopic examination of bone tissue confirmed there was reduced degeneration and porosity within the endplates, as well as reduced separation between them, in the treated mice. This suggests the anti-senescence drug can prevent the degeneration and remodeling associated with aging or spine instability.
Finally, because porous endplates allow new nerves to grow into the endplate bone, causing sensitivity, the authors looked at whether senescent osteoclasts play a role in this process. They tested for two markers of nerve fibers in the endplates of mice, as well as markers of new blood vessels, and found that mice treated with the anti-senescence drug had fewer nerves and blood vessels within the endplate than untreated mice. This suggests there is an ongoing dysfunctional production of new bone tissue within the spinal endplate in the aging or injured spine, and that treatment to remove the senescent osteoclasts could halt this process.
Taken together, these findings suggest a potential role for anti-senescent drugs such as Navitoclax in treating spine pain, but this would need to be further evaluated in clinical trials before the treatment could be used in patients with lower back pain.
Dayu Pan, Kheiria Gamal Benkato, Xuequan Han, Jinjian Zheng, Vijay Kumar, Mei Wan, Junying Zheng, Xu Cao. Senescence of endplate osteoclasts induces sensory innervation and spinal pain. eLife, 2023 DOI: 10.7554/eLife.92889.1
eLife. “Drug that kills off sleeping bone cells could treat lower back pain.” ScienceDaily. ScienceDaily, 14 November 2023. <www.sciencedaily.com/releases/2023/11/231114143708.htm>.
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