Researchers have identified a bone-driven signaling pathway that may explain how spinal degeneration leads to chronic pain.
Low back pain (LBP) ranks among the most widespread health conditions across the globe. It affects people at every stage of life and creates a significant strain on healthcare systems. For many individuals, the pain becomes long-lasting, disrupting sleep, limiting mobility, and reducing quality of life. In most cases, however, physicians are unable to pinpoint a specific structural problem, which makes effective long-term treatment difficult.
Research published in the journal Bone Research points to a possible new approach. The study suggests that a hormone-based therapy could ease chronic back pain by preventing abnormal growth of pain-related nerves within damaged areas of the spine. Led by Dr. Janet L. Crane of the Center for Musculoskeletal Research in the Department of Orthopedic Surgery at Johns Hopkins University School of Medicine in the United States, the work sheds light on how bone cells may play an unexpected role in regulating pain during spinal degeneration.
“During spinal degeneration, pain-sensing nerves grow into regions where they normally do not exist. Our findings show that parathyroid hormone can reverse this process by activating natural signals that push these nerves away,” says Dr. Crane.
Parathyroid Hormone and Spinal Degeneration
Parathyroid hormone (PTH) is naturally produced by the parathyroid glands and is essential for controlling calcium balance and maintaining healthy bone turnover. Manufactured versions of PTH are already prescribed to treat osteoporosis. Earlier research hinted that these therapies might also reduce pain linked to bone damage, but the underlying biological explanation had not been fully understood.
To explore this question, the research team turned to three different mouse models that reflect common drivers of spinal degeneration: aging, surgically induced mechanical instability, and inherited vulnerability.
Using these models, the scientists examined how degenerative changes affect bone architecture and nerve growth at the same time. Mice were given daily injections of PTH for periods lasting from two weeks up to two months, while a comparison group received inactive treatments. The team then analyzed spinal tissue with high-resolution imaging and assessed the animals’ responses to pressure, heat, and movement.
Within one to two months, mice treated with PTH showed noticeable improvements in their vertebral endplates, which form the interface between spinal discs and vertebrae. The endplates became denser and more structurally sound. These physical changes were accompanied by functional benefits, as treated animals handled pressure more comfortably, reacted more slowly to heat, and displayed higher levels of activity than those that did not receive the hormone.
Reducing Abnormal Nerve Growth
The researchers also examined nerve fibers within the spinal tissue. In degenerative conditions, pain-sensing nerves frequently spread into areas where they are not normally found, which can heighten sensitivity and worsen discomfort. The study showed that treatment with PTH led to a marked reduction in these abnormal nerve fibers, based on measurements using indicators such as PGP9.5 and CGRP.
Additional experiments clarified the biological mechanism behind this effect. PTH activated osteoblasts—cells responsible for building bone—prompting them to release a protein known as Slit3. This protein serves as a directional signal that discourages nerve fibers from growing into vulnerable regions of the spine.
Laboratory studies supported this mechanism. When nerve cells were grown in the presence of Slit3, their outgrowth was limited, producing shorter and less invasive extensions. However, when Slit3 was genetically eliminated from osteoblasts in mice, PTH treatment no longer reduced nerve growth or eased pain-related responses. The researchers also identified a regulatory protein called FoxA2 that plays a role in turning on Slit3 production when PTH is present, helping explain how hormonal signals influence nerve activity.
While the research was carried out in animal models, the findings may offer insight into why some people treated with PTH-based therapies for osteoporosis report less back pain. The authors stress that studies in humans are still needed before these results can be translated into clinical care.
“Our study suggests that PTH treatment of LBP during spinal degeneration may reduce aberrant innervation, laying the foundation for future clinical trials exploring the efficacy of PTH as a disease-modifying and pain-relief treatment for spinal degeneration,” concludes Dr. Crane.
Reference: “PTH induced osteoblast Slit3 to decrease aberrant sensory innervation in degenerated vertebral endplates to relieve low back pain in mice” by Weixin Zhang, Arryn D. Otte, Zhuolun Wang, Sisir Kumar Barik, Mei Wan, Xu Cao and Janet L. Crane, 22 January 2026, Bone Research.
DOI: 10.1038/s41413-025-00488-z
This research was supported by the U.S. Department of Health & Human Services NIH National Institute on Aging under Award Number P01AG066603 (to Xu Cao), Sub-Project 6878 (to Janet Crane).
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3 Comments
redirecting nerve cells is the only way I could even fathom how to do this but there has to be a way to redirect the pain while stabilizing where said nerve cells can set in the body. redirecting the pain would need pressurizing and decompressing the pain cortex until it is fatigue. this would be a bit painful for said patient but not as much as some procedures. my guess would be use banana peel properties as the condensed potasium could make it bearable. using an enhanced laser on the spine could work. pressurize a sugar with nitrogen and ionizing titanium could make a laser if you used helium as a quantum base for the laser pressurre
Where is the “pain cortex” located? Is pain capable of thinking?
What do you mean by an “enhanced laser?” In what way are you proposing to ‘enhance’ a laser?
What do you mean by “banana peel properties?” I thought that most of the potassium existed in the inner fruit, not the skin that protects it. Do you have a citation that you can provide that demonstrates that the skin of a banana is a superior source of potassium compared to the fruit?
What kind of sugar are you proposing to use? Sucrose, glucose, or fructose? What do you mean by pressurizing it? Are you proposing pressurizing an aqueous solution of sugar with nitrogen? What is that supposed to do?
What do you mean by the term “quantum base?” I’m unfamiliar with it. A quick online search only returns that name of a company.
What state of matter, or phase, are you proposing that titanium be used to have ionizing properties?
Why do you think that you are above using accepted capitalizations?
Unfortunate enough to have long-term experience with LBP (e.g., a fall at work in 1995 with early retirement in 2001; twenty-five years of weekly chiropractic treatments) I’ve found at least two highly relevant factors not included in the article. First, my (Dr. Arthur F. Coca’s, by 1935) kind of multiple mainstream medically ignored sub-acute (nearly subclinical) non-IgE-mediated food (primarily, in my case) allergy reactions can cause muscle weaknesses which can allow the spine to lose alignment with minimal exertion. Also, in the course of fighting allergy related low grade inflammation, calcium may be relocated from the bones, nerves and or teeth to try to maintain the blood at an optimal pH (about 7.35) with standard blood serum testing for calcium being unreliable (“ionic” testing is said to be reliable), possibly resulting in osteoporosis and premature degeneration. PTH hormone treatments might be a valuable adjunct therapy but, to this senior lay male survivor’s experience, allergic sensitivities, inflammation levels and calcium sufficiency should be adequately determined and addressed, first.