NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.
Nat Commun
; 15(1): 1705, 2024 Feb 24.
Article
en En
| MEDLINE
| ID: mdl-38402219
ABSTRACT
Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells - monocytes, macrophages, and neutrophils - were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
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Amidohidrolasas
Límite:
Animals
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article