Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation

Authors

Ibdanelo Cortez
Caitlyn M Gaffney
Riddhi Vichare
Caitlin V Crelli
Lu Liu
Eric Lee
Jules Edralin
James M Nichols
Hoang Vu Pham
Syed Mehdi
Jelena M Janjic
Andrew J Shepherd

Publication Date

1-1-2024

Journal

International Journal of Nanomedicine

Abstract

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 days post-injury than 7 days post-injury. The COX-2 inhibiting nanoemulsion drove widespread anti-inflammatory changes in cytokine expression in polytrauma-affected peripheral nerves. Our data shed new light on the modulation of inflammation by injured nerve input and demonstrate macrophage-targeted nanoimmunomodulation can produce rapid and sustained pain relief following complex injuries.

Keywords

Animals, Macrophages, Male, Female, Celecoxib, Cyclooxygenase 2 Inhibitors, Mice, Cyclooxygenase 2, Multiple Trauma, Emulsions, Mice, Inbred C57BL, Pain, Disease Models, Animal, Cytokines, Immunomodulation, nerve injury, muscle contusion, inflammation, celecoxib, nanoemulsion, COX-2

Comments

PMID: 39050880