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 (CGRP8-37 , 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-HT1A (wAy-100,135, 450 µg/paw) or 5-HT3 (
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.