Neutrophil-Derived COX-2 has a Key Role during Inflammatory Hyperalgesia

Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized...

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Bibliographic Details
Published in:Inflammation 2022-12, Vol.45 (6), p.2280-2293
Main Authors: Carvalho, Nathalia Santos, Lemes, Julia Borges Paes, Pagliusi Jr, Marco, Machado, Ana Carolina dos Santos, Malange, Kauê Franco, Pral, Laís Passariello, Fachi, José Luís, Nishijima, Catarine Massucato, dos Santos, Gilson Gonçalves, Tambeli, Claudia Herrera, Sartori, Cesar Renato, Vinolo, Marco Aurélio Ramirez, Parada, Carlos Amilcar
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cyclooxygenase-1
Cyclooxygenase-2
Hyperalgesia
IL-1β
Immunology
Inflammation
Internal Medicine
Leukocyte migration
Leukocytes (neutrophilic)
Neutrophils
Original Article
Pain perception
Pathology
Pharmacology/Toxicology
Rheumatology
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Summary:Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in inflammatory conditions. Although it is well known that neutrophil cells are the first to arrive at the inflamed site and the major source of COX-2 is still unknown, the specific role of neutrophil-derived COX-2 in the pain process is. Thus, in the present study, we demonstrate for the first time that neutrophil-derived COX-2 plays a key role in peripheral inflammatory hyperalgesia. Conditional knockout mice for COX-2 in neutrophils (COX-2  fl/fl: Mrp8cre± ) exhibited higher pain sensitivity after carrageenan (CG) injection and long-lasting IL-1β-induced hyperalgesia compared with the control group (COX-2  fl/fl ). Also, CG-induced inflammation in COX-2  fl/fl: Mrp8cre± mice showed COX-1 overexpression, and increased neutrophil migration and pro-inflammatory cytokines ( e.g ., IL-1β and CXCL1). These findings revealed that neutrophil COX-2 has an important role in the regulation of inflammatory hyperalgesia.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-022-01690-5