Extensive Periosteal Injury During Fracture Induces Long-Term Pain in Mice.

Area of Science:

• Orthopedics
• Neuroscience
• Pain Research

Background:

• Bone fractures are a major public health concern requiring surgical intervention for healing.
• The periosteum, a highly innervated bone layer, is vulnerable to injury during trauma.
• The impact of periosteal injury on fracture pain is not well understood.

Purpose of the Study:

• To investigate the effect of extensive periosteal injury on fracture pain and bone healing.
• To establish a mouse model for studying long-term orthopedic fracture pain.

Main Methods:

• Induction of periosteal injury via mechanical resection during unilateral transverse fracture in mice.
• Assessment of pain using von Frey and dynamic weight bearing tests.
• Analysis of nerve innervation and gene expression in dorsal root ganglia (DRG) via immunofluorescence.
• Evaluation of bone healing using Faxitron X-ray imaging.

Main Results:

• Extensive periosteal injury resulted in severe, long-term pain lasting up to 12 weeks.
• Increased neurofilament heavy polypeptide (NF200+) nerve innervation and calcitonin gene-related peptide (CGRP+) neurons were observed in the DRG.
• Myeloid immune cell presence in the DRG was elevated.
• Fractures with periosteal injury showed reduced callus size, indicating impaired bone healing.

Conclusions:

• Extensive periosteal injury significantly exacerbates fracture pain and delays bone healing.
• This study identifies periosteal injury as a critical factor in long-term fracture pain.
• The developed mouse model can be used to study chronic orthopedic pain mechanisms.