title: Involvement of c-Myc-mediated transient receptor potential melastatin 8 expression in oxaliplatin-induced cold allodynia in mice.
abstract: BACKGROUND
  Oxaliplatin, a platinum-based chemotherapeutic agent, induces acute cold allodynia and dysesthesia. Cold-sensitive transient receptor potential channels (TRPM8 and TRPA1) have been implicated as candidates to mediate oxaliplatin-induced cold allodynia and hyperalgesia, but precise roles of these channels remain unclear. In this study, we investigated the role of TRPM8 in oxaliplatin-induced cold allodynia.
  
  
  METHODS
  Oxaliplatin was injected intraperitoneally in mice. Cold allodynia was evaluated by the acetone test. Expression levels of TRPM8 mRNA and protein were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively.
  
  
  RESULTS
  Oxaliplatin-induced cold allodynia was alleviated by the TRPM8 blockers N-(2-aminoethyl)-N-[4-(benzyloxy)-3-methoxybenzyl]-N'-(1S)-1-(phenyl) ethyl] urea and TC-I 2014. Oxaliplatin increased the expression levels of TRPM8 mRNA and protein in the dorsal root ganglia and plantar skin, respectively. Prophylactic administration of the c-Myc inhibitor 10058-F4 prevented cold allodynia and the increase of TRPM8 mRNA after oxaliplatin injection.
  
  
  CONCLUSIONS
  These results suggest that oxaliplatin induces cold allodynia through the increase of c-Myc-mediated TRPM8 expression in primary sensory neurons.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Mizoguchi
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: andoht@pha.u-toyama.ac.jp.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.affiliation: Department of Organomolecular Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakura
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced*; D008297:Male; D051379:Mice; D009944:Organoplatinum Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077150:Oxaliplatin; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D012867:Skin / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013844:Thiazoles / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*; D014508:Urea / Q000494:pharmacology
chemical_list: C524814:5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one; D001593:Benzyl Compounds; C000620773:N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)-N'-(1S)-1-(phenyl) ethyl)urea; D009944:Organoplatinum Compounds; D016271:Proto-Oncogene Proteins c-myc; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D013844:Thiazoles; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000077150:Oxaliplatin; D014508:Urea
keywords: Cold allodynia; Oxaliplatin; TRPM8; c-Myc