Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Neutrophil migration is responsible for tissue damage observed in inflammatory diseases. Neutrophils are also implicated in inflammatory nociception, but mechanisms of their participation have not been elucidated. In the present study, we addressed these mechanisms in the carrageenan‐induced mechani...

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Published in:Journal of leukocyte biology Vol. 83; no. 4; pp. 824 - 832
Main Authors: Cunha, Thiago M., Verri, Waldiceu A., Schivo, Ieda R., Napimoga, Marcelo H., Parada, Carlos A., Poole, Stephen, Teixeira, Mauro M., Ferreira, Sergio H., Cunha, Fernando Q.
Format: Journal Article
Language:English
Published: United States Society for Leukocyte Biology 01.04.2008
Subjects:
Animals
Carrageenan - pharmacology
Cell Culture Techniques
Chemokine CXCL1 - blood
cytokines
Cytokines - blood
Dinoprostone - metabolism
Hindlimb - blood supply
hyperalgesia
Hyperalgesia - blood
Hyperalgesia - physiopathology
Inflammation - blood
Inflammation - physiopathology
Interleukin-1 - blood
Male
Neutrophils - cytology
Neutrophils - drug effects
Neutrophils - physiology
nociception
pain
Pain - blood
Pain - physiopathology
Pain Threshold
PGE2
Polysaccharides - pharmacology
Rats
Rats, Wistar
Reaction Time
Skin Physiological Phenomena
Tumor Necrosis Factor-alpha - blood
ISSN:0741-5400, 1938-3673
Online Access:Get full text
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Summary:Neutrophil migration is responsible for tissue damage observed in inflammatory diseases. Neutrophils are also implicated in inflammatory nociception, but mechanisms of their participation have not been elucidated. In the present study, we addressed these mechanisms in the carrageenan‐induced mechanical hypernociception, which was determined using a modification of the Randall‐Sellito test in rats. Neutrophil accumulation into the plantar tissue was determined by the contents of myeloperoxidase activity, whereas cytokines and PGE2 levels were measured by ELISA and radioimmunoassay, respectively. The pretreatment of rats with fucoidin (a leukocyte adhesion inhibitor) inhibited carrageenan‐induced hypernociception in a dose‐ and time‐dependent manner. Inhibition of hypernociception by fucoidin was associated with prevention of neutrophil recruitment, as it did not inhibit the hypernociception induced by the direct‐acting hypernociceptive mediators, PGE2 and dopamine, which cause hypernociception, independent of neutrophils. Fucoidin had no effect on carrageenan‐induced TNF‐α, IL‐1β, and cytokine‐induced neutrophil chemoattractant 1 (CINC‐1)/CXCL1 production, suggesting that neutrophils were not the source of hypernociceptive cytokines. Conversely, hypernociception and neutrophil migration induced by TNF‐α, IL‐1β, and CINC‐1/CXCL1 was inhibited by fucoidin, suggesting that neutrophils are involved in the production of direct‐acting hypernociceptive mediators. Indeed, neutrophils stimulated in vitro with IL‐1β produced PGE2, and IL‐1β‐induced PGE2 production in the rat paw was inhibited by the pretreatment with fucoidin. In conclusion, during the inflammatory process, the migrating neutrophils participate in the cascade of events leading to mechanical hypernociception, at least by mediating the release of direct‐acting hypernociceptive mediators, such as PGE2. Therefore, the blockade of neutrophil migration could be a target to development of new analgesic drugs.
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ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0907654