Hormone Treatment May Alleviate Chronic Low Back Pain by Limiting Abnormal Nerve Growth
Published in Bone Research, Volume 14, January 22, 2026
A recent study indicates that a hormone treatment may alleviate chronic low back pain by limiting abnormal nerve growth within damaged spinal tissue. The research, led by Dr. Janet L. Crane from the Center for Musculoskeletal Research, Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, identifies a biological mechanism through which bone cells influence pain signals in degenerating spines.
Context of Low Back Pain
Low back pain (LBP) is a prevalent global health issue, affecting individuals across age groups and contributing significantly to healthcare burdens. Many patients experience persistent discomfort that can interfere with daily activities. In numerous cases, a clear structural cause for LBP remains unidentified, complicating long-term treatment strategies.
Research increasingly suggests that the vertebral endplate—the layer separating spinal discs from vertebrae—plays a crucial role. In aging spines, these endplates can expand, become porous, and develop abnormal sensory innervation, contributing to pain.
Study Objectives and Methodology
The Johns Hopkins team aimed to understand how these physiological changes in degenerating spines contribute to pain and whether they could be altered. Dr. Crane noted that during spinal degeneration, pain-sensing nerves grow into regions where they typically do not exist. The study investigated whether parathyroid hormone (PTH), involved in regulating calcium levels and bone remodeling, could reverse this process. While synthetic forms of PTH are used for osteoporosis treatment and previous studies hinted it might reduce bone-related pain, the specific biological mechanism remained unclear.
Researchers utilized three mouse models designed to replicate common causes of spinal degeneration: natural aging, mechanical instability induced by surgery, and genetic susceptibility to intervertebral disc degeneration. These models allowed for the analysis of degeneration's effects on both bone structure and nerve growth.
Mice received daily PTH injections for periods ranging from two weeks to two months, while control groups were administered inactive solutions. Spinal tissue was subsequently examined using high-resolution imaging, and the animals' sensitivity to pressure, heat, and physical activity was tested.
Key Findings
After one to two months of treatment, PTH-treated mice demonstrated improvements in the structure of their vertebral endplates, which became less porous and more stable. Concurrently, these mice exhibited reduced pain-related behaviors, including improved pressure tolerance, slower withdrawal from heat stimuli, and increased physical activity compared to untreated animals.
Analysis of nerve fibers within the spine revealed that in degenerated tissue, pain-sensing nerves frequently grow into abnormal locations. PTH treatment significantly reduced the number of these aberrant fibers, as indicated by markers such as PGP9.5 and CGRP.
Elucidating the Mechanism
Further experiments clarified the mechanism responsible for these observed effects. The research team discovered that PTH stimulated osteoblasts (the cells responsible for bone formation) to produce a protein named Slit3. Slit3 functions as a guidance signal that repels growing nerve fibers, thereby preventing their invasion into sensitive spinal areas.
Laboratory tests confirmed that Slit3 directly inhibited nerve growth; when nerve cells were exposed to Slit3 in culture, their extensions became shorter. Conversely, when Slit3 was genetically removed from osteoblasts in mice, PTH did not reduce nerve growth or alleviate pain. The team also identified FoxA2, a regulatory protein involved in activating Slit3 production in response to PTH.
Broader Research Context
This study expands upon earlier research by the same group, which had linked lower back pain to uncoupled bone remodeling in aging spines. Previously, the researchers showed that osteoclasts (cells that break down bone) secrete Netrin-1, a factor that attracts sensory nerves into degenerated endplates. The acidic environments created by osteoclasts were found to promote nerve ingrowth and pain. The current study identifies Slit3, produced in response to PTH, as a counterbalance capable of repelling nociceptive fibers.
Implications and Future Directions
While conducted in animal models, these findings may offer an explanation for reports of reduced back pain among some patients receiving PTH-based treatments for osteoporosis in clinical studies, even though pain was not the primary endpoint of those trials.
"Dr. Crane concluded that the study suggests PTH treatment for low back pain during spinal degeneration may reduce abnormal nerve innervation, establishing a basis for future clinical trials to explore PTH's efficacy as a disease-modifying and pain-relief treatment for spinal degeneration."
Researchers emphasize that further human studies are necessary before these findings can be applied in clinical practice. Next steps for the research include investigating how these mechanisms translate to humans, determining which patients with specific endplate changes might be most likely to benefit, and further examining how Slit3 influences bone vasculature and neural signaling in different spinal regions, as well as how genetic background may shape nerve-bone interactions during degeneration.