A study published in the journal *Bone Research* reports that parathyroid hormone (PTH) reduced pain-related behaviors in mouse models of spinal degeneration, apparently by strengthening vertebral endplates and triggering bone-cell signals that repel pain-sensing nerve fibers. The work was led by Dr. Janet L. Crane of Johns Hopkins University School of Medicine.
Low back pain (LBP) is among the most widespread health problems globally, and in many cases clinicians cannot identify a clear structural cause—making long-term treatment difficult.
A study published in Volume 14 of Bone Research describes an experimental approach in mice that targets biological changes seen during spinal degeneration, rather than aiming only to blunt symptoms. The research team tested parathyroid hormone (PTH)—a hormone involved in calcium regulation and bone remodeling, with synthetic forms already used to treat osteoporosis—in three mouse models meant to mirror common drivers of spinal degeneration: aging, surgically induced mechanical instability, and genetic susceptibility.
Across treatment windows ranging from two weeks to two months, mice received daily injections of PTH while control animals received an inactive solution. In the models assessed after one to two months of treatment, the study reports that PTH was associated with denser, more stable vertebral endplates—thin layers that separate spinal discs from vertebrae—and with reduced sensitivity in tests linked to pain behaviors, including responses to pressure and heat. The researchers also reported increased activity in treated animals.
Tissue analysis focused on abnormal growth of sensory nerve fibers into damaged spinal regions. The study says PTH treatment reduced these aberrant nerve fibers based on the markers PGP9.5 and CGRP.
To explain how a bone-directed hormone might alter pain signaling, the researchers identified a pathway in which PTH stimulates osteoblasts (bone-forming cells) to produce Slit3, a guidance protein that can repel nerve growth. Laboratory experiments described in the report found that Slit3 directly limited nerve outgrowth. The study further reports that when Slit3 was removed from osteoblasts in mice, PTH no longer reduced nerve growth or improved pain-related measures, and it identified the regulatory protein FoxA2 as part of the mechanism that activates Slit3 production in response to PTH.
"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," Crane said.
The researchers cautioned that the findings come from animal studies and said further work in humans would be required before any clinical use for back pain. "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," Crane said.
The ScienceDaily summary of the study said the research was supported by the U.S. National Institute on Aging under an NIH award and subproject listed in the release.
