Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation

DOI

10.2147/IJN.S460418

Document Type

Journal Article

Publication Date

1-1-2024

Publication Title

International journal of nanomedicine

Volume

19

First Page

7253

Last Page

7271

Keywords

celecoxib, COX-2, inflammation, muscle contusion, nanoemulsion, nerve injury

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.

Open Access

Gold

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