NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.

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 NAA

SUBMITTER: Fotio Y 

PROVIDER: S-EPMC10894261 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature