Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system.
BACKGROUND
Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC-030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 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 Frey 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 TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
L M S
LM
Pereira
R C P
RC
Lima-Júnior
A X C
AX
Bem
C G
CG
Teixeira
L S
LS
Grassi
R P
RP
Medeiros
R D
RD
Marques-Neto
R B
RB
Callado
K S
KS
Aragão
D V T
DV
Wong
M L
ML
Vale
G A C
GA
Brito
R A
RA
Ribeiro
D000005:Abdomen / Q000502:physiology; D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced; D003556:Cystitis / Q000139:chemically induced / Q000473:pathology; D015232:Dinoprostone / Q000494:pharmacology; D004723:Endorphins / Q000502:physiology*; D007069:Ifosfamide; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009149:Mustard Plant; D009569:Nitric Oxide / Q000502:physiology*; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000523:psychology; D010533:Peritoneal Lavage; D010812:Physical Stimulation; D010938:Plant Oils; D011687:Purines / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*
C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D018906:Antineoplastic Agents, Alkylating; D004723:Endorphins; D010938:Plant Oils; D011687:Purines; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D016595:Misoprostol; D009569:Nitric Oxide; D015232:Dinoprostone; C027793:mustard oil; D007069:Ifosfamide