Year: 2024
Type: article
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.
DOI: 10.2147/ijn.s460418
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,836
Awards: G293715275, G4119534169, LONG-ACTING NONOPIOID ANALGESIC (LANA) NANOMEDICINE FOR RAPID, SINGLE-DOSE, SUSTAINED PAIN CONTROL AND REHABILITATION SUPPORT AFTER NEUROMUSCULOSKELETAL INJURY. NEW AWARD., Long-Acting Nonopioid Analgesic (LANA) Nanomedicine for Rapid, Single-Dose, Sustained Pain Control and Rehabilitation Support After Neuromusculoskeletal Injury, G5850682332, G7761418987, Cancer Center Support Grant
OpenAlex ID: W4400790822