Role of IL-18 in overt pain-like behaviour in mice.
There are evidences that targeting IL-18 might be beneficial to inhibit inflammatory symptoms, including hypernociception (decrease in nociceptive threshold). The mechanism of IL-18 mechanical hypernociception depends on endothelin in rats and mice. However, the role of IL-18 in overt pain-like behaviour remains undetermined. Therefore, we addressed the role of IL-18 in writhing response induced by intraperitoneal (i.p.) injection of phenyl-p-benzoquinone (PBQ) and acetic acid in mice. Firstly, it was detected that PBQ and acetic acid i.p. injection induced a dose-dependent number of writhes in Balb/c mice. Subsequently, it was observed that the PBQ - but not the acetic acid-induced writhes were diminished in IL-18 deficient ((-/-)) mice. Therefore, considering that IFN-gamma, endothelin and prostanoids mediate IL-18-induced mechanical hypernociception, we also investigated the role of these mediators in the same model of writhing response in which IL-18 participates. It was noticed that PBQ-induced writhes were diminished in IFN-gamma(-/-) mice and by the treatment with bosentan (mixed endothelin ETA/ETB receptor antagonist), BQ 123 (cyclo[DTrp-DAsp-Pro-DVal-Leu], selective endothelin ETA receptor antagonist), BQ 788 (N-cys-2,6 dimethylpiperidinocarbonyl-l-methylleucyl-d-1-methoxycarboyl-d-norleucine, selective endothelin ETB receptor antagonist) or indomethacin (cycloxigenase inhibitor). Thus, IL-18, IFN-gamma, endothelin acting on endothelin ETA and ETB receptors, and prostanoids mediate PBQ-induced writhing response in mice. To conclude, these results further advance the understanding of the physiopathology of overt pain-like behaviour, and suggest for the first time a role for IL-18 in writhing response in mice.
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, 14049-900-Ribeirão Preto, São Paulo, Brazil. waldiceujr@yahoo.com.br <waldiceujr@yahoo.com.br>
Waldiceu A
WA
Verri
Thiago M
TM
Cunha
Danilo A
DA
Magro
Andressa C
AC
Domingues
Silvio M
SM
Vieira
Guilherme R
GR
Souza
Foo Y
FY
Liew
Sérgio H
SH
Ferreira
Fernando Q
FQ
Cunha
D000818:Animals; D016227:Benzoquinones / Q000633:toxicity; D007371:Interferon-gamma / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010146:Pain / Q000503:physiopathology*; D011453:Prostaglandins / Q000502:physiology; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology
D016227:Benzoquinones; D020382:Interleukin-18; D011453:Prostaglandins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C029322:phenylbenzoquinone; D007371:Interferon-gamma