Etodolac Blocks the Allyl Isothiocyanate-Induced Response in Mouse Sensory Neurons by Selective TRPA1 Activation
| Autor: | Takashi Kyoi, Masaki Nogawa, Koyuki Tajima, Sunao Ito, Naoki Inoue |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Agonist Sensory Receptor Cells medicine.drug_class TRPV2 TRPV1 Pain CHO Cells Pharmacology Mice Cricetulus Transient Receptor Potential Channels Dorsal root ganglion Isothiocyanates Cricetinae Ganglia Spinal medicine TRPM8 Animals Humans Etodolac TRPA1 Cation Channel Cells Cultured Behavior Animal Cyclooxygenase 2 Inhibitors Chemistry food and beverages General Medicine Analgesics Non-Narcotic HEK293 Cells Nociception medicine.anatomical_structure Nociceptor Calcium Neuroscience psychological phenomena and processes medicine.drug |
| Zdroj: | Pharmacology. 90:47-54 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Background and Purpose: 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. Experimental Approach: Ca2+ 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. Results: Etodolac induced Ca2+ influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca2+ influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca2+ influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca2+ influx induced by AITC. Conclusion and Implication: 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|