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

Yannick Fotio, Alex Mabou Tagne, Erica Squire, Hye-lim Lee, Connor M. Phillips, Kayla Chang, Faizy Ahmed, Andrew S. Greenberg, S. Armando Villalta, Vanessa M. Scarfone, Gilberto Spadoni, Marco Mor and Daniele Piomelli ()
Additional contact information
Yannick Fotio: University of California Irvine
Alex Mabou Tagne: University of California Irvine
Erica Squire: University of California Irvine
Hye-lim Lee: University of California Irvine
Connor M. Phillips: University of California Irvine
Kayla Chang: University of California Irvine
Faizy Ahmed: University of California Irvine
Andrew S. Greenberg: Tufts University
S. Armando Villalta: University of California Irvine
Vanessa M. Scarfone: University of California Irvine
Gilberto Spadoni: Università di Urbino “Carlo Bo,”
Marco Mor: Università di Parma
Daniele Piomelli: University of California Irvine

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46139-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46139-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46139-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().