Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B1 and B2 receptor knockout mice

Item Type:	Article
Title:	Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B1 and B2 receptor knockout mice
Creators Name:	Ferreira, J. and Campos, M.M. and Pesquero, J.B. and Araújo, R.C. and Bader, M. and Calixto, J.B.
Abstract:	Experiments were designed to investigate the role of kinin B1 and B2 receptors in Freund's adjuvant (CFA)-induced inflammation and nociception responses by the use of B1 and B2 null mutant mice. Intradermal (i.d.) injection of CFA produced time-dependent and marked hyperalgesic responses in both ipsilateral and contralateral paws of wild-type mice. Gene disruption of the kinin B2 receptor did not interfere with CFA-induced hyperalgesia, but ablation of the gene of the B1 receptor reduced the hyperalgesia in both ipsilateral (48±13%, at 12 h) and contralateral (91±22%, at 12 h) paws. Treatment of wild-type mice with the selective B1 antagonist des-Arg9-[Leu8]-BK (150 nmol/kg, s.c.) reduced CFA-evoked thermal hyperalgesia, to an extent which was similar to that observed in mice lacking kinin B1 receptor. I.d. injection of CFA produced a time-related and long-lasting (up to 72 h) increase in paw volume in wild-type mice. A similar effect was observed in B1 knockout mice. In mice lacking B2 receptor, the earlier stage of the CFA-induced paw oedema (6 h) was significantly greater compared with the wild-type animals, an effect which was almost completely reversed (76±5%) by des-Arg9-[Leu8]-BK. This data demonstrates that kinin B1 receptor, but not B2 receptor, exerts a critical role in controlling the persistent inflammatory hyperalgesia induced by CFA in mice, while B2 receptor appears to have only a minor role in the amplification of the earlier stage of CFA-induced paw oedema formation. The results of the present study, taken together with those of previous studies, suggest that B1 receptor antagonists represent a potential target for the development of new drugs to treat persistent inflammatory pain.
Keywords:	B1 and B2 Receptor, Complete Freund's Adjuvant, Hyperalgesia, Knockout Mice, Paw Oedema, Animals, Mice
Source:	Neuropharmacology
ISSN:	0028-3908
Publisher:	Elsevier / Pergamon Press
Volume:	41
Number:	8
Page Range:	1006-1012
Date:	1 December 2001
Official Publication:	https://doi.org/10.1016/S0028-3908(01)00142-3
PubMed:	View item in PubMed

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