• Eur. J. Pharmacol. · Feb 2003

    Combined action of vasoactive amines and bradykinin mediates allergen-evoked thermal hyperalgesia in rats.

    • Tatiana R Lavich, Renato S B Cordeiro, João B Calixto, Patrícia M R e Silva, and Marco A Martins.
    • Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz-FIOCRUZ, Av. Brasil 4365, Caixa Postal 926, Rio de Janeiro, Brazil.
    • Eur. J. Pharmacol. 2003 Feb 21;462(1-3):185-92.

    AbstractThe ability of allergens to induce hyperalgesia in immunoglobulin E (IgE)-sensitized rats was investigated. The left hind paws of Wistar rats were sensitized with intraplantar injections of IgE anti-dinitrophenylated bovine serum albumin monoclonal antibody, and challenged with dinitrophenylated bovine serum albumin 24 h later. Allergen challenge yielded rapid thermal hyperalgesia and oedema formation in the ipsilateral paws, both reaching a plateau from 15 min to 3 h, and both diminishing thereafter. Allergen-evoked hyperalgesia was inhibited by intraperitoneal treatment with meclizine or methysergide, histamine and 5-hydroxytryptamine receptor antagonists. There was also sensitivity to local treatment with either bradykinin B(1) or B(2) receptor antagonists, des-Arg(9)-[Leu(8)]-bradykinin or D-arginyl-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (Hoe 140). Anaphylactic hyperalgesia was mimicked by the combined administration of histamine, 5-hydroxytryptamine and bradykinin at doses which were ineffective when injected alone. This synergistic effect was abolished by treatment with either meclizine, methysergide, Hoe 140 or des-Arg(9)-[Leu(8)]-bradykinin. Our findings show that local thermal hyperalgesia is a feature of allergen-evoked inflammation, and that a synergistic interaction among bradykinin, 5-hydroxytryptamine and histamine plays a critical role in this phenomenon.

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