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

• Published in: European journal of pharmacology Vol. 462; no. 1; pp. 185 - 192
• Main Authors: Lavich, Tatiana R, Cordeiro, Renato S.B, Calixto, João B, e Silva, Patrı́cia M.R, Martins, Marco A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 21-02-2003; Elsevier
• Subjects: Allergens - immunology; Allergy; Animals; Biological and medical sciences; Bradykinin; Bradykinin - administration & dosage; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Bradykinin Receptor Antagonists; Cyproheptadine - pharmacology; Dinitrophenols - metabolism; Dose-Response Relationship, Drug; Drug Synergism; Edema - chemically induced; Edema - prevention & control; Histamine - administration & dosage; Histamine H1 Antagonists - pharmacology; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - immunology; Hyperalgesia - prevention & control; Immunoglobulin E - immunology; Inflammation; Male; Meclizine - pharmacology; Medical sciences; Methysergide - pharmacology; Pain - chemically induced; Pain - immunology; Pain - prevention & control; Rats; Rats, Wistar; Serotonin - administration & dosage; Serotonin Antagonists - pharmacology; Serum Albumin, Bovine - administration & dosage; Serum Albumin, Bovine - metabolism; Time Factors; Vasoactive amine; Allergy; Vasoactive amine; Inflammation; Bradykinin; Hyperalgesia
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02947-3

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.