Researchers have found that parathyroid hormone (PTH), already used to treat osteoporosis, may ease chronic back pain by preventing pain-triggering nerves from growing into damaged spinal areas. This discovery could lead to entirely new treatments that address the root cause of back pain rather than just masking symptoms. The findings come from a study led by scientists at Johns Hopkins University School of Medicine and published in the journal Bone Research in 2026.

What Causes Chronic Back Pain When Doctors Can't Find a Clear Problem?

Low back pain (LBP) is one of the most widespread health issues globally, affecting people across all age groups and creating significant strain on healthcare systems. For many people, the pain becomes long-lasting, disrupting work, sleep, and everyday life. The challenge is that in most cases, doctors cannot pinpoint a clear structural cause, which makes effective long-term treatment difficult .

During spinal degeneration, something unexpected happens: pain-sensing nerves grow into regions where they normally do not exist. This abnormal nerve growth is a key driver of chronic pain, but until now, scientists did not fully understand how to stop it. The new research reveals that PTH may be the answer.

How Does Parathyroid Hormone Reduce Pain-Causing Nerve Growth?

Parathyroid hormone is naturally produced by the parathyroid glands and plays a key role in regulating calcium levels and bone remodeling. Synthetic versions of PTH are already used to treat osteoporosis, a condition where bones become weak and brittle. Earlier research hinted that these treatments might also reduce bone-related pain, but the underlying biological mechanism was not well understood .

To explore this further, researchers used three mouse models that replicate common causes of spinal degeneration: natural aging, surgically induced mechanical instability, and genetic susceptibility. The mice received daily injections of PTH for periods ranging from two weeks to two months, while control animals were given inactive solutions. Researchers then examined spinal tissue using high-resolution imaging and measured responses to pressure, heat, and movement .

After one to two months of treatment, mice treated with PTH showed clear improvements in their vertebral endplates, the thin layers that separate spinal discs from vertebrae. These structures became denser and more stable. At the same time, treated mice showed reduced sensitivity to pain, tolerated pressure better, responded more slowly to heat, and displayed increased activity compared to untreated animals .

The researchers also examined nerve fibers within the spine. In damaged tissue, pain-sensing nerves often extend into areas where they do not typically belong, increasing discomfort. The study found that PTH treatment significantly reduced these abnormal nerve fibers, based on markers such as PGP9.5 and CGRP .

The Molecular Mechanism: How PTH Pushes Pain Nerves Away

Further analysis revealed the underlying mechanism. PTH stimulated osteoblasts, the cells responsible for building bone, to produce a protein called Slit3. This protein acts as a guidance signal that repels growing nerve fibers, preventing them from entering sensitive regions of the spine .

Laboratory experiments confirmed that Slit3 directly limits nerve growth. When nerve cells were exposed to Slit3, their extensions became shorter and less invasive. In contrast, when researchers removed Slit3 from osteoblasts in mice, PTH no longer reduced nerve growth or improved pain responses. The team also identified a regulatory protein called FoxA2 that helps trigger Slit3 production in response to PTH, offering deeper insight into how hormonal signals influence nerve behavior .

"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," explained Dr. Janet L. Crane.

Dr. Janet L. Crane, Associate Professor of Pediatrics and Director of the Pediatric Bone Health Program at Johns Hopkins University School of Medicine

Steps to Understanding This Potential Treatment Approach

• The Problem: Chronic back pain often occurs without a clear structural cause, making it difficult to treat effectively with current approaches that focus on symptoms rather than root causes.
• The Discovery: Parathyroid hormone activates bone cells to produce Slit3 protein, which acts as a natural barrier that prevents pain-sensing nerves from growing into damaged spinal tissue.
• The Evidence: Animal studies showed that PTH treatment improved spinal structure, reduced pain sensitivity, and decreased abnormal nerve growth over one to two months of daily injections.
• The Mechanism: The process involves a chain of molecular signals: PTH stimulates osteoblasts, which produce Slit3, which then repels growing nerve fibers and prevents them from entering sensitive spinal regions.

What Does This Mean for People With Back Pain?

Although these findings come from animal studies, they may help explain why some patients receiving PTH-based treatments for osteoporosis report reduced back pain. This discovery opens the door to a completely different approach to treating chronic back pain, one that targets the biological root cause rather than just managing symptoms .

The researchers note that further studies in humans are needed before this approach can be used clinically. However, the findings are promising enough that they have laid the groundwork for future clinical trials.

"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," concluded Dr. Crane.

Dr. Janet L. Crane, Associate Professor of Pediatrics at Johns Hopkins University School of Medicine

This research was supported by the U.S. Department of Health and Human Services National Institutes of Health (NIH) National Institute on Aging. The study represents a significant shift in how scientists think about chronic back pain, moving from simply managing discomfort to understanding and preventing the biological changes that cause it in the first place.