Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation.

Autor:	Cortez I; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Gaffney CM; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Vichare R; School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA., Crelli CV; School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA., Liu L; School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA., Lee E; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Edralin J; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Nichols JM; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Pham HV; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Mehdi S; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Janjic JM; School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA., Shepherd AJ; Laboratories of Neuroimmunology, Department of Symptom Research, the University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Jazyk:	angličtina
Zdroj:	International journal of nanomedicine [Int J Nanomedicine] 2024 Jul 18; Vol. 19, pp. 7253-7271. Date of Electronic Publication: 2024 Jul 18 (Print Publication: 2024).
DOI:	10.2147/IJN.S460418
Abstrakt:	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. Competing Interests: The authors report no conflicts of interest in this work. (© 2024 Cortez et al.)
Databáze:	MEDLINE
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