Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B-1 and B-2 receptor knockout mice

Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B-1 and B-2 receptor knockout mice

Autor Ferreira, J. Google Scholar
Campos, M. M. Google Scholar
Pesquero, J. B. Google Scholar
Araujo, R. C. Google Scholar
Bader, M. Google Scholar
Calixto, J. B. Google Scholar
Instituição Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
MDC Mol Med
Resumo Experiments were designed to investigate the rule of kinin B-1 and B-2 receptors in Freund's adjuvant (CFA)-induced inflammation and nociception responses by the use of B-1 and B-2 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 B-2 receptor did not interfere with CFA-induced hyperalgesia, but ablation of the gene of the B-1 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 B-1 antagonist des-Arg(9)-[Leu(8)]-BK (150 nmol/kg, s.c.) reduced CFA-evoked thermal hyperalgesia, to;an extent which ss-as similar to that observed in mice lacking kinin B-1 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 B-1 knockout mice. in mice lacking B-2 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-Arg(9)-[Leu(8)]-BK. This data demonstrates that kinin B-1 receptor, but not B-2 receptor. exerts a critical role in controlling the persistent inflammatory hyperalgesia induced by CFA in mice. while B-2 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 B-1 receptor antagonists represent a potential target for tire development of new drugs to treat persistent inflammatory pain. (C) 2001 Published by Elsevier B.V.
Palavra-chave B-1 and B-2 receptor
knockout mice
hyperalgesia
paw oedema
complete Freund's adjuvant
Idioma Inglês
Data de publicação 2001-12-01
Publicado em Neuropharmacology. Oxford: Pergamon-Elsevier B.V., v. 41, n. 8, p. 1006-1012, 2001.
ISSN 0028-3908 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 1006-1012
Fonte http://dx.doi.org/10.1016/S0028-3908(01)00142-3
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000173268800011
Endereço permanente http://repositorio.unifesp.br/handle/11600/26672

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