Researchers have discovered a bone-mediated signaling pathway that could help explain how spinal degeneration results in chronic pain.
Low back pain (LBP) is one of the most common health problems worldwide. It affects individuals of all ages and places a heavy burden on healthcare systems. For many people, the pain becomes chronic, interfering with sleep, restricting movement, and diminishing overall quality of life. Yet in most cases, doctors cannot identify a clear structural cause, making long-term treatment challenging.
A study published in Bone Research highlights a potential new strategy. The findings suggest hormone therapy may ease chronic back pain by blocking abnormal nerve growth in the spine. Led by Dr. Janet L. Crane at Johns Hopkins’ Center for Musculoskeletal Research found that bone cells may unexpectedly help control pain in spinal degeneration.
“During spinal degeneration, pain-sensing nerves extend into areas where they are not typically found. “Our research shows parathyroid hormone can push these nerves away by activating natural signals,” Dr. Crane explains.
Parathyroid Hormone and Spinal Degeneration
Parathyroid hormone (PTH), produced by the parathyroid glands, plays a key role in regulating calcium levels and supporting healthy bone remodeling. Synthetic forms of PTH are already used to treat osteoporosis. Previous studies suggested these treatments might also ease bone-related pain, though the biological mechanism remained unclear.
To investigate further, researchers used three mouse models representing common causes of spinal degeneration: aging, surgically created mechanical instability, and genetic susceptibility.
They studied how degeneration influenced both bone structure and nerve growth. The mice received daily PTH injections for two weeks to two months, while control animals were given inactive treatments. The team then examined spinal tissue with advanced imaging and tested the animals’ sensitivity to pressure, heat, and movement.
After one to two months of treatment, mice given PTH showed clear improvements in their vertebral endplates—the structures connecting spinal discs to vertebrae. The endplates became thicker and more stable. These structural gains were matched by functional improvements: treated mice tolerated pressure better, were less sensitive to heat, and remained more active compared with untreated animals.
Limiting Abnormal Nerve Growth
The team also analyzed nerve fibers in spinal tissue. During degeneration, pain-sensing nerves often extend into areas they don’t occupy, increasing sensitivity and discomfort. The study found that PTH treatment significantly reduced these abnormal nerve fibers, as shown by markers such as PGP9.5 and CGRP.
Further experiments revealed how this happens. PTH stimulated osteoblasts—the cells that form bone—to produce a protein called Slit3. Slit3 acts as a guidance signal, preventing nerve fibers from growing into fragile regions of the spine.
Lab tests confirmed this effect: nerve cells exposed to Slit3 developed shorter, less invasive projections. But when Slit3 was genetically removed from osteoblasts in mice, PTH no longer curbed nerve growth or relieved pain-related behaviors. The researchers also identified a regulatory protein, FoxA2, which helps activate Slit3 production in response to PTH, clarifying how hormonal signals can influence nerve activity.
Although this research was conducted in animal models, the results could help explain why some osteoporosis patients receiving PTH-based treatments experience reduced back pain. The authors emphasize that human studies are still necessary before these findings can be applied in clinical practice.
“Our study indicates that PTH therapy for low back pain in spinal degeneration may limit abnormal nerve growth, providing a basis for future clinical trials to evaluate PTH as both a disease-modifying and pain-relieving treatment,” concludes Dr. Crane.
Read the original article on: SciTechDaily
Read more: Common Eye Bacteria Connected to Alzheimer’s Disease