title: Etodolac blocks the allyl isothiocyanate-induced response in mouse sensory neurons by selective TRPA1 activation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Exploratory Department, Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan. n.inoue@po.nippon-shinyaku.co.jp
authors: Naoki
authors: N
authors: Inoue
authors: Sunao
authors: S
authors: Ito
authors: Masaki
authors: M
authors: Nogawa
authors: Koyuki
authors: K
authors: Tajima
authors: Takashi
authors: T
authors: Kyoi
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016466:CHO Cells; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017308:Etodolac / Q000494:pharmacology* / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000502:physiology*
chemical_list: D018712:Analgesics, Non-Narcotic; D052246:Cyclooxygenase 2 Inhibitors; D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D017308:Etodolac; C004471:allyl isothiocyanate; D002118:Calcium