Hormone therapy may curb nerve growth linked to chronic low back pain

Low back pain is one of the most common health problems worldwide and can limit work, sleep and daily activities. In many patients, clinicians cannot pinpoint a single structural driver, complicating long-term management. One suspected mechanism in spinal degeneration is aberrant innervation: pain-sensing nerves extend into tissue regions where they typically do not occur, potentially increasing sensitivity and discomfort.

The study, led by Dr. Janet L. Crane (Johns Hopkins University School of Medicine), tested whether PTH can influence degeneration-related nerve changes. The team examined three mouse models that mimic common causes of spinal degeneration:

• natural aging
• mechanical instability after surgery
• genetic susceptibility

Mice received daily PTH injections for two weeks to two months, while control animals received inactive solutions. The researchers used high-resolution imaging to assess spinal tissue and tested sensitivity to pressure and heat, alongside measures of physical activity.

After one to two months, PTH-treated mice showed improvements in vertebral endplates, described as less porous and more stable. Functional outcomes also shifted: treated animals tolerated pressure better, withdrew more slowly from heat and were more active than untreated mice.

The team then focused on nerve fibers inside the spine. In degenerated tissue, pain-sensing nerves can grow into abnormal locations. PTH treatment reduced the number of these fibers, quantified using markers including PGP9.5 and CGRP.

Dr. Crane summarizes the proposed mechanism: “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,” says Dr. Crane.

PTH is produced by the parathyroid glands and regulates calcium and bone remodelling; synthetic forms are already prescribed for osteoporosis. In this study, PTH stimulated osteoblasts (bone-forming cells) to produce Slit3, a guidance protein that repels growing nerve fibers.

Laboratory experiments supported this pathway: Slit3 directly inhibited nerve growth in cell culture, leading to shorter, less invasive nerve extensions. Importantly, when Slit3 was genetically removed from osteoblasts in mice, PTH no longer reduced nerve growth or relieved pain-related measures. The researchers also identified FoxA2 as a regulatory protein involved in activating Slit3 production in response to PTH.

MEDICA-tradefair.com; Source: The Johns Hopkins University School of Medicine