Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B1 and B2 receptor knockout mice
Neuropharmacology, 2001•Elsevier
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 (id) 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 …
adjuvant (CFA)-induced inflammation and nociception responses by the use of B1 and B2
null mutant mice. Intradermal (id) 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 …
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.
Elsevier