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  • Etodolac blocks the allyl isothiocyanate-induced response in mouse sensory neurons by selective TRPA1 activation.

Etodolac blocks the allyl isothiocyanate-induced response in mouse sensory neurons by selective TRPA1 activation.

Pharmacology (2012-06-29)
Naoki Inoue, Sunao Ito, Masaki Nogawa, Koyuki Tajima, Takashi Kyoi
ABSTRACT

The excitability of nociceptors is modulated by the transient receptor potential cation channel, ankyrin subfamily, member 1 (TRPA1). We have previously reported that etodolac, a nonsteroidal anti-inflammatory drug, attenuates mechanical allodynia in a mouse model of neuropathic pain by a mechanism that is independent of cyclooxygenase inhibition. Here, we investigate the role of TRPA1 in the mechanism of the antinociceptive action of etodolac in vitro and in vivo. Ca(2+) influx was measured in HEK-293 cells expressing mouse TRPA1 and in mouse dorsal root ganglion (DRG) neurons. The effect of etodolac on the nociceptive behavior induced in mice by the TRPA1 agonist allyl isothiocyanate (AITC) was also measured. Etodolac induced Ca(2+) influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca(2+) influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca(2+) influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca(2+) influx induced by AITC. Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Allyl isothiocyanate, contains BHT as stabilizer, 95%
Supelco
Allyl isothiocyanate, PESTANAL®, analytical standard
Sigma-Aldrich
Allyl isothiocyanate, ≥95%, FCC
Sigma-Aldrich
Etodolac
Etodolac for peak identification, European Pharmacopoeia (EP) Reference Standard
Etodolac, European Pharmacopoeia (EP) Reference Standard

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