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Endothelins contribute towards nociception induced by antigen in ovalbumin‐sensitised mice
Author(s) -
Piovezan Anna P,
D'OrléansJuste Pedro,
Frighetto Monica,
Souza Glória E P,
Henriques Maria G M O,
Rae Giles A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705663
Subject(s) - ovalbumin , licking , chemistry , endocrinology , medicine , agonist , antagonist , nociception , receptor antagonist , receptor , pharmacology , antigen , immunology
The contribution of endogenous endothelins to nociceptive responses elicited by ovalbumin (OVA) in the hind‐paw of mice sensitised to this antigen (50 μ g OVA+5 mg Al(OH) 3 , s.c., 14 days beforehand) was investigated. Sensitised mice exhibited greater nocifensive responsiveness to intraplantar (i.pl.) OVA (total licking time over first 30 min: 85.2±14.6 s at 0.3 μ g; 152.6±35.6 s at 1 μ g) than nonsensitised animals (29.3±7.4 s at 1 μ g). Nocifensive responses of sensitised mice to 0.3 μ g OVA were inhibited by morphine (3 mg kg −1 , s.c.) or local depletion of mast cells (four daily i.pl. injections of compound 48/80). Pretreatment with i.v. bosentan (mixed ET A /ET B receptor antagonist; 52 μ mol kg −1 ) or A‐122722.5 (selective ET A receptor antagonist; 6 μ mol kg −1 ) reduced OVA‐induced licking from 124.8±20.6 s to 45.7±13.0 s and 64.2±12.1 s, respectively, whereas A‐192621.1 (selective ET B receptor antagonist; 25 μ mol kg −1 ) enhanced them to 259.2±39.6 s. Local i.pl. pretreatment with BQ‐123 or BQ‐788 (selective ET A or ET B receptor antagonists, respectively, each at 3 nmol) reduced OVA‐induced licking (from 106.2±15.2 to 57.0±9.4 s and from 118.6±10.5 to 76.8±14.7 s, respectively). Sarafotoxin S6c (selective ETB receptor agonist, 30 pmol, i.pl., 30 min after OVA) induced nocifensive responses in OVA‐sensitised, but not in nonsensitised, animals. Compound 48/80 (0.3 μ g, i.pl.) induced nocifensive responses per se and potentiated those induced by i.pl. capsaicin (0.1 μ g). Treatment with BQ‐123 (3 nmol, i.pl.) reduced only the hyperalgesic effect of compound 48/80, whereas BQ‐788 (3 nmol) was ineffective. Thus, immune‐mediated Type I hypersensitivity reactions elicit mast cell‐ and endothelin‐dependent nociception in the mouse hind‐paw, which are mediated locally by both ET A and ET B receptors. The nocifensive response to antigen is amenable to blockade by systemic treatment with dual ET A /ET B or selective ET A receptor antagonists, but is sharply potentiated by systemic selective ET B receptor antagonist treatment. The apparently distinct roles played by ET B receptors in this phenomenon at local and other sites remain to be characterised.British Journal of Pharmacology (2004) 141 , 755–763. doi: 10.1038/sj.bjp.0705663