Ra. Ribeiro et al., Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice, EUR J PHARM, 387(1), 2000, pp. 111-118
Intraperitoneal administration of zymosan and acetic acid induced a dose-de
pendent nociceptive writhing response in mice. Lavage of the peritoneal cav
ities with saline reduced the number of total resident peritoneal cells and
caused a proportional decrease in the nociceptive responses induced by the
se stimuli. Furthermore, the specific reduction of the peritoneal mast cell
population by intraperitoneal administration of compound 48/80 also reduce
d the nociceptive responses induced by zymosan and acetic acid. In contrast
, enhancement of the peritoneal macrophage population by pretreatment of th
e cavities with thioglycollate caused an increase in the number of writhes
induced by both stimuli. These data suggest that the nociceptive responses
induced by zymosan and acetic acid are dependent upon the peritoneal reside
nt macrophages and mast cells. These cells modulate the nociceptive respons
e induced by zymosan and acetic acid via release of tumour necrosis factor
alpha (TNF-alpha), interleukin 1 beta and interleukin 8. This suggestion is
supported by the following observations: (a) pretreatment of the peritonea
l cavities with antisera against these cytokines reduced the nociceptive re
sponses induced by these stimuli: (b) peritoneal cells harvested from cavit
ies injected with zymosan or acetic acid released both interleukin 1 beta a
nd TNF-alpha; (c) although individual injection of TNF-alpha, interleukin 1
beta or interleukin 8 did not induce the nociceptive effect, intraperitone
al injection of a mixture of these three recombinant cytokines caused a sig
nificant nociceptive writhing response. In conclusion, our results suggest
that the nociceptive activity of zymosan and acetic acid in the writhing mo
del is due to the release of TNF-alpha, interleukin 1 beta and interleukin
8 by resident peritoneal macrophages and mast cells. (C) 2000 Elsevier Scie
nce B.V. All rights reserved.