Antinociceptive effect of the calcium-binding protein MRP-14 and the role played by neutrophils on the control of inflammatory pain.
Macrophages secrete a variety of chemical mediators that play a central role in the pathophysiology of inflammatory pain. Therefore, the activation or deactivation of these cells in an inflammatory focus could modulate the intensity of the algogenic response. Based on these premises and on our previous demonstration that the calcium-binding protein MRP-14, highly expressed in neutrophils, deactivates activated macrophages in vitro, we decided to investigate the role of MRP-14 and of neutrophils in the control of inflammatory pain in mice. Our results show that this protein is endowed with antinociceptive activity. When tested in the writhing model it was able to inhibit pain response but did not change the behavior of the animals in the hot plate test. This observation indicates that MRP-14 down-regulates inflammatory but not central pain. Using a model of acute neutrophilic peritonitis induced by glycogen, a close correlation between neutrophil migration and antinociception was detected. Surgical adrenalectomy demonstrated that the antinociceptive response induced by glycogen was not due to endogenous liberation of glucocorticoids. The treatment of animals either with a monoclonal antibody anti-MRP-14 or a monoclonal antibody that depletes the animals of neutrophils reverts the antinociceptive response observed in the glycogen-induced peritonitis. These data define the calcium-binding protein MRP-14 as a novel mediator for the control of inflammatory pain and consequently discloses an anti-inflammatory role for the neutrophil.
Giorgi
R
R
Laboratory of Pathophysiology, Butantan Institute, São Paulo, Brazil.
Pagano
R L
RL
Dias
M A
MA
Aguiar-Passeti
T
T
Sorg
C
C
Mariano
M
M
D000005:Abdomen; D000315:Adrenalectomy; D000818:Animals; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D040501:Calgranulin A; D040502:Calgranulin B; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D006003:Glycogen / Q000494:pharmacology; D006358:Hot Temperature; D007509:Irritants / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D009619:Nociceptors / Q000276:immunology*; D010146:Pain / Q000276:immunology* / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D007509:Irritants; D006003:Glycogen