Faculty, Staff and Student Publications
Publication Date
1-1-2024
Journal
Muscle Nerve
Abstract
Introduction/aims: Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion.
Methods: We developed a closed-impact mouse model of muscle contusion and a macrophage-targeted near-infrared fluorescent nanoemulsion. Closed-impact contusions were delivered to the lower left limb. Pain sensitivity, gait dysfunction, and inflammation were assessed in the days and weeks post-contusion. Macrophage accumulation was imaged in vivo by injecting i.v. near-infrared nanoemulsion.
Results: Despite hindpaw hypersensitivity persisting for several weeks, disruptions to gait and grip strength typically resolved within 10 days of injury. Using non-invasive imaging and immunohistochemistry, we show that macrophage density peaks in and around the affected muscle 3 day post-injury and quickly subsides. However, macrophage density in the ipsilateral sciatic nerve and dorsal root ganglia (DRG) increases more gradually and persists for at least 14 days.
Discussion: In this study, we demonstrate pain sensitivity is influenced by the degree of lower muscle contusion, without significant changes to gait and grip strength. This may be due to modulation of pain signaling by macrophage proliferation in the sciatic nerve, upstream from the site of injury. Our work suggests chronic pain developing from muscle contusion is driven by macrophage-derived neuroinflammation in the peripheral nervous system.
Keywords
Mice, Animals, Pain, Macrophages, Contusions, Muscles, Inflammation
DOI
10.1002/mus.28001
PMID
37929655
PMCID
PMC11851331
PubMedCentral® Posted Date
2-25-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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