Hormone Therapy Shows Promise in Alleviating Chronic Back Pain
Low back pain (LBP) is a widespread health problem, impacting individuals of all ages and placing a significant strain on healthcare systems. Many patients experience persistent discomfort that interferes with daily life, yet often, doctors are unable to pinpoint a specific structural cause, complicating long-term treatment strategies.
A new study, published in Volume 14 of the journal Bone Research on , suggests that hormone therapy may offer relief from chronic back pain by modulating nerve signals 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, provides new insights into the relationship between bone cells and pain signaling in degenerating spines.
“During spinal degeneration, pain-sensing nerves grow into regions where they normally do not exist,” explains Dr. Crane. “Our findings show that parathyroid hormone can reverse this process by activating natural signals that push these nerves away.”
Parathyroid Hormone and Spinal Degeneration
Parathyroid hormone (PTH), produced by the parathyroid glands, plays a crucial role in regulating calcium levels and bone remodeling. Synthetic forms of PTH are currently used in the treatment of osteoporosis. Previous research has hinted at a potential for these treatments to reduce bone-related pain, but the underlying biological mechanisms remained unclear.
To investigate further, Dr. Crane and her team conducted experiments using three mouse models designed to replicate common causes of spinal degeneration: natural aging, mechanical instability induced by surgery, and genetic predisposition. These models allowed the researchers to analyze the effects of degeneration on both bone structure and nerve growth. The mice received daily PTH injections for periods ranging from two weeks to two months, with a control group receiving inactive solutions. Subsequently, the researchers examined the animals’ spinal tissue using high-resolution imaging and assessed their sensitivity to pressure, heat, and physical activity.
After one to two months of treatment, mice treated with PTH demonstrated improvements in the structure of their vertebral endplates – the thin layers separating spinal discs from vertebrae. These endplates exhibited reduced porosity and increased stability. Treated mice displayed a greater tolerance to pressure, a slower withdrawal response to heat, and increased overall activity levels compared to the untreated control group.
Nerve Fiber Reduction and the Role of Slit3
The research team also analyzed nerve fibers within the spine. In degenerated tissue, pain-sensing nerves often extend into abnormal locations, contributing to increased sensitivity and discomfort. The study revealed that PTH treatment significantly reduced the number of these fibers, as indicated by markers such as PGP9.5 and CGRP.
Further investigation uncovered the mechanism behind this process. PTH stimulated osteoblasts – cells responsible for bone formation – to produce a protein called Slit3. Slit3 functions as a guidance signal, repelling growing nerve fibers and preventing their invasion into sensitive areas.
Laboratory experiments confirmed that Slit3 directly inhibits nerve growth. When nerve cells were exposed to Slit3 in a laboratory setting, their extensions became shorter and less invasive. Conversely, when the researchers genetically removed Slit3 from osteoblasts in mice, PTH no longer effectively reduced nerve growth or alleviated pain.
FoxA2 and PTH Signaling
The team also identified a regulatory protein, FoxA2, which plays a role in activating Slit3 production in response to PTH. This finding provides further insight into how hormonal signals translate into changes in nerve behavior.
Implications for Human Treatment
While this study was conducted on animal models, the results may offer an explanation for why some patients receiving PTH-based treatments for osteoporosis report a reduction in back pain. The researchers emphasize the need for further human studies before these findings can be translated into clinical practice.
“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,” Dr. Crane concludes.
