Comprehensive gene expression profiling in the prefrontal cortex links immune activation and neutrophil infiltration to antinociception.
J Neurosci
; 32(1): 35-45, 2012 Jan 04.
Article
em En
| MEDLINE
| ID: mdl-22219268
ABSTRACT
Functional neuroimaging studies have implicated the prefrontal cortex (PFCTX) in descending modulation of pain and the placebo effect. This study was performed to elucidate comprehensive PFCTX gene expression in an animal model of persistent trigeminal pain. Adult male C57BL/6J mice received facial carrageenan injection and showed sustained increase in nociceptive responses. Microarray analyses of differentially expressed genes in the PFCTX at 3 d after injection showed "immune system process" as the dominant ontology term and increased mRNA expression of S100a8, S100a9, Lcn2, Il2rg, Fcgr1, Fcgr2b, C1qb, Ptprc, Ccl12, and Cd52 were verified by RT-PCR. Upregulation of S100A8, S100A9, and lipocalin 2 (LCN2) were confirmed by Western blots, and cells in the PFCTX were double immunolabeled with MPO, indicating they were neutrophils. Analyses of blood of facial carrageenan-injected mice also showed increased mRNA expression of these markers, suggesting transmigration of activated neutrophils into the brain. Other immune-related genes, Il2rg, Fcgr2b, C1qb, Ptprc, and Ccl12 were upregulated in the PFCTX but not blood. Approximately 70% of S100A9-positive cells in the PFCTX of carrageenan-injected mice were located in capillaries adherent to endothelial cells, whereas 30% were within the brain parenchyma. Carrageenan-injected mice showed significantly reduced nociceptive responses after injection of C terminus of murine S100A9 protein in the lateral ventricles and PFCTX but not somatosensory barrel cortex. Together, these findings demonstrate activation of immune-related genes in the PFCTX during inflammatory pain and highlight an exciting role of neutrophils in linking peripheral inflammation with immune activation of the PFCTX and antinociception.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Pré-Frontal
/
Perfilação da Expressão Gênica
/
Infiltração de Neutrófilos
/
Dor Crônica
/
Inibição Neural
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Singapura