| First Author | Fotio Y | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 1705 |
| PubMed ID | 38402219 | Mgi Jnum | J:346576 |
| Mgi Id | MGI:7609311 | Doi | 10.1038/s41467-024-46139-5 |
| Citation | Fotio Y, et al. (2024) NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice. Nat Commun 15(1):1705 |
| abstractText | 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-alpha (PPAR-alpha). 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-alpha recruitment. Mice lacking NAAA in CD11b(+) cells - monocytes, macrophages, and neutrophils - were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-alpha 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. |
