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Mechanisms underlying transient receptor potential ankyrin 1 ( TRPA1 )‐mediated hyperalgesia and edema
Author(s) -
PerinMartins Andressa,
Teixeira Juliana Maia,
Tambeli Claudia H.,
Parada Carlos Amílcar,
Fischer Luana
Publication year - 2013
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns5.12010
Subject(s) - hyperalgesia , pharmacology , chemistry , edema , calcitonin gene related peptide , transient receptor potential channel , pyrilamine , antagonist , anesthesia , receptor , medicine , nociception , neuropeptide , biochemistry
The aim of this study was to investigate the mechanisms that contribute to hyperalgesia and edema induced by TRPA1 activation. The injection of allyl isothiocyanate ( AITC , 50, 100, or 300 µg/paw) into the rat's hind paw induced dose and time‐dependent hyperalgesia and edema, which were blocked by the selective TRPA1 antagonist, HC 030031 (1,200 µg/paw), or by treatment with antisense oligodeoxynucleotide (four daily intrathecal injections of 5 nmol). These results demonstrate that the hyperalgesia and edema induced by AITC depend on TRPA1 activation. AITC ‐induced hyperalgesia and edema were significantly reduced by treatment with neurokinin 1 (L‐703,606, 38 µg/paw) or calcitonin gene‐related peptide ( CGRP 8‐37 , 5 µg/paw) receptor antagonists, with a mast cell degranulator (compound 48/80, four daily injections of 1, 3, 10, and 10 µg/paw) or with H1 (pyrilamine, 400 µg/paw), 5‐ HT 1A (wAy‐100,135, 450 µg/paw) or 5‐ HT 3 (tropisetron, 450 µg/paw) receptor antagonists. Pre‐treatment with a selectin inhibitor (fucoidan, 20 mg/kg) significantly reduced AITC ‐induced hyperalgesia, edema, and neutrophil migration. Finally, a cyclooxygenase inhibitor (indomethacin, 100 µg/paw), a β1 (atenolol, 6 µg/paw) or a β2 ( ICI 118, 551, 1.5 µg/paw) adrenoceptor antagonist also significantly reduced AITC ‐induced hyperalgesia and edema. Together, these results demonstrate that TRPA1 mediates some of the key inflammatory mechanisms, suggesting a key role of this receptor in pain and inflammation.