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B lockade of TRPA 1 with HC ‐030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system
Author(s) -
Pereira L.M.S.,
LimaJúnior R.C.P.,
Bem A.X.C.,
Teixeira C.G.,
Grassi L.S.,
Medeiros R.P.,
MarquesNeto R.D.,
Callado R.B.,
Aragão K.S.,
Wong D.V.T.,
Vale M.L.,
Brito G.A.C.,
Ribeiro R.A.
Publication year - 2013
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2012.00177.x
Subject(s) - chemistry , pharmacology , zymosan , nociception , nitric oxide , opioid , biochemistry , medicine , receptor , organic chemistry , in vitro
Background Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A 1 channels ( TRPA 1), which is modulated by the TRPA 1 antagonist HC ‐030031. However, a few studies report the role of TRPA 1 in visceral pain. Therefore, we investigated the participation of TRPA 1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels. Methods Mice were treated with vehicle or HC ‐030031 (18.75–300 mg/kg) before ifosfamide (400 mg/kg), 0.75% mustard oil (50 μL /colon), acetic acid 0.6% (10 mL /kg), zymosan (1 mg/cavity) or misoprostol (1 μg/cavity) injection. Visceral nociception was assessed through the electronic von F rey test or the writhing response. Ifosfamide‐administered mice were euthanized for bladder analysis. The involvement of nitric oxide and the opioid system were investigated in mice injected with ifosfamide and mustard oil, respectively. The participation of resident peritoneal cells in acetic acid‐, zymosan‐ or misoprostol‐induced nociception was also evaluated. Results HC ‐030031 failed to protect animals against ifosfamide‐induced bladder injury ( p > 0.05). However, a marked antinociceptive effect against ifosfamide, mustard oil, acetic acid, zymosan and misoprostol was observed ( p < 0.05). Neither L ‐arginine (600 mg/kg) nor naloxone (2 mg/kg) could reverse the antinociceptive effect of HC ‐030031. The reduction of the peritoneal cell population inhibited the acetic acid and zymosan‐related writhes without interfering with the misoprostol effect. Conclusions Our findings suggest that the blockade of TRPA 1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.