Premium
Analgesic effects evoked by a CCR 2 antagonist or an anti‐ CCL 2 antibody in inflamed mice
Author(s) -
LloriánSalvador María,
Pevida Marta,
GonzálezRodríguez Sara,
Lastra Ana,
FernándezGarcía MaríaTeresa,
Hidalgo Agustín,
Baamonde Ana,
Menéndez Luis
Publication year - 2016
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12182
Subject(s) - ccr2 , chemokine , pharmacology , ccl2 , hyperalgesia , carrageenan , inflammation , antagonist , medicine , chemistry , immunology , receptor , nociception , chemokine receptor
Abstract Chemokine CCL 2, also known as monocyte chemoattractant protein‐1 ( MCP ‐1), is a molecule that in addition to its well‐established role in chemotaxis can also act as nociceptor sensitizer. The upregulation of this chemokine in inflamed tissues could suggest its involvement in inflammatory hypernociception. Thus, we have measured CCL 2 levels in mice with acute or chronic inflammation due to the intraplantar (i.pl.) injection of carrageenan or complete Freund's adjuvant ( CFA ), respectively, and we have studied whether inflammatory hyperalgesia or allodynia could be attenuated by blocking CCR 2 receptors or neutralizing CCL 2 with an anti‐ CCL 2 antibody. A remarkable increase in CCL 2 concentration was detected by ELISA in paw homogenates coming from carrageenan‐ or CFA ‐inflamed mice, being its expression mainly localized in macrophages, as shown by immunohistochemical assays. The s.c. (0.3–3 mg/kg) or i.pl. (0.3–3 μg) administration of the CCR 2 antagonist, RS 504393, dose dependently inhibited thermal hyperalgesia measured in acutely or chronically inflamed mice, whereas s.c. administration of this drug did not reduce inflammatory mechanical allodynia. Furthermore, the inhibition of inflammatory hyperalgesia after the administration of an anti‐ CCL 2 antibody (0.1–1 μg; i.pl.) suggests that CCL 2 could be the endogenous chemokine responsible for CCR 2‐mediated hyperalgesic effects. Besides, the acute administration of the highest antihyperalgesic dose of RS 504393 assayed did not reduce paw tumefaction or modify the presence of inflammatory cells. These results indicate that the blockade of the CCL 2/ CCR 2 system can counteract inflammatory hyperalgesia, being this antinociceptive effect unrelated to a decrease in the inflammatory reaction.