title: Combined action of vasoactive amines and bradykinin mediates allergen-evoked thermal hyperalgesia in rats.
abstract: The 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.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz-FIOCRUZ, Av. Brasil 4365, Caixa Postal 926, Rio de Janeiro, Brazil.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: Lavich
authors.forename: Renato S B
authors.initials: RS
authors.lastname: Cordeiro
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Patrícia M R
authors.initials: PM
authors.lastname: e Silva
authors.forename: Marco A
authors.initials: MA
authors.lastname: Martins
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003533:Cyproheptadine / Q000494:pharmacology; D004140:Dinitrophenols / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006632:Histamine / Q000008:administration & dosage*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008468:Meclizine / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000008:administration & dosage*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors
chemical_list: D000485:Allergens; D065168:Bradykinin Receptor Antagonists; D004140:Dinitrophenols; D006634:Histamine H1 Antagonists; D012702:Serotonin Antagonists; D012710:Serum Albumin, Bovine; D003533:Cyproheptadine; D012701:Serotonin; D007073:Immunoglobulin E; D008468:Meclizine; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D006632:Histamine; D001920:Bradykinin; D008784:Methysergide