Low back pain (LBP) is one of the most prevalent health problems worldwide, affecting people of all ages and placing a significant burden on healthcare systems. For many people, pain is long-term and interferes with work, sleep, and daily life. However, in most cases, doctors cannot identify a clear structural cause, making effective long-term treatment difficult.
New research published in Volume 14 of the journal bone research Our findings suggest that hormone-based treatments may help relieve chronic low back pain by reducing abnormal nerve growth within injured spinal cord tissue. The study was led by Dr. Janet L. Crane of the Center for Musculoskeletal Research in the Department of Orthopedics at Johns Hopkins University School of Medicine. The findings provide new insight into how bone cells influence pain signaling in degenerating spines.
“During spinal degeneration, pain-sensing nerves grow into areas where they would normally not be present. Our findings show that parathyroid hormone can reverse this process by activating natural signals that push these nerves away,” said Dr. Crane.
Understanding parathyroid hormone and its effects
Parathyroid hormone (PTH) is naturally produced by the parathyroid glands and plays an important role in regulating calcium levels and bone remodeling. A synthetic version of PTH is already used to treat osteoporosis. Previous studies suggested that these treatments may also reduce bone-related pain, but the underlying biological mechanisms were not well understood.
To investigate this further, the research team used three mouse models that recapitulate common causes of spinal degeneration: natural aging, surgically induced mechanical instability, and genetic susceptibility. These models have allowed scientists to study how degeneration affects both bone structure and nerve growth. Mice were injected with PTH daily for a period ranging from 2 weeks to 2 months, and control animals received an inert solution. The researchers then used high-resolution imaging to examine the spinal tissue and measure its response to pressure, heat, and movement.
Improving spinal structure and reducing pain sensitivity
After one to two months of treatment, mice treated with PTH showed clear improvements in the vertebral endplates, the thin layers that separate the intervertebral discs and vertebrae. These structures became denser and more stable. At the same time, treated mice were less sensitive to pain, tolerated pressure better, responded more slowly to heat, and showed increased activity compared to untreated mice.
How PTH inhibits the growth of nerves that cause pain
The researchers also examined nerve fibers within the spine. In damaged tissue, pain-sensing nerves often extend into areas where they don’t belong, increasing discomfort. This study found that PTH treatment significantly reduced these abnormal nerve fibers based on markers such as PGP9.5 and CGRP.
Further analysis revealed the underlying mechanism. PTH stimulated osteoblasts, cells involved in bone formation, to produce a protein called Slit3. This protein acts as a guiding signal to repel growing nerve fibers, preventing them from entering sensitive areas of the spine.
Slit3 protein and molecular pathway
Laboratory experiments confirmed that Slit3 directly limits neural growth. When neurons are exposed to Slit3, their elongation becomes shorter and less invasive. In contrast, when the researchers removed Slit3 from mouse osteoblasts, PTH no longer reduced nerve growth or improved pain responses. The research team also identified a regulatory protein called FoxA2 that helps trigger the production of Slit3 in response to PTH, providing deeper insight into how hormonal signals influence neural behavior.
What this means for the future of low back pain treatment
Although these findings come from animal studies, they may help explain why some patients receiving PTH-based treatments for osteoporosis report reduced back pain. The researchers note that further studies in humans are needed before this approach can be used clinically.
“Our study suggests that PTH treatment of LBP during spinal degeneration may attenuate aberrant innervation and may lay the foundation for future clinical trials exploring the efficacy of PTH as a disease-modifying and analgesic treatment for spinal degeneration,” concluded Dr. Crane.
About the researcher
Dr. Janet L. Crane is an associate professor of pediatrics and director of the Pediatric Bone Health Program at Johns Hopkins University School of Medicine. She also holds a position at the Center for Musculoskeletal Research in the Department of Orthopedics. She earned her bachelor’s degree in nutrition from the University of Missouri and her medical degree from the University of Maryland, Baltimore. Her research focuses on metabolic bone disease and skeletal fragility, and she has published extensively on bone remodeling, metabolic bone disease, and mechanisms of skeletal pain.
This research was supported by the U.S. Department of Health and Human Services NIH National Institute on Aging under Award Number P01AG066603 (Xu Cao), Subproject 6878 (Janet Crane).
