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.

CONCLUSION:

These results suggest that oxaliplatin induces cold allodynia through the increase of c-Myc-mediated TRPM8 expression in primary sensory neurons.

• Authors: Shizuka Mizoguchi, Tsugunobu Andoh, Takayuki Yakura, Yasushi Kuraishi
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 68 Issue 3 Pg. 645-8 (Jun 2016) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 27031051 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• 5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one
• Benzyl Compounds
• N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)-N'-(1S)-1-(phenyl) ethyl)urea
• Organoplatinum Compounds
• Proto-Oncogene Proteins c-myc
• TRPA1 Cation Channel
• TRPM Cation Channels
• TRPM8 protein, mouse
• Thiazoles
• Transient Receptor Potential Channels
• Trpa1 protein, mouse
• Oxaliplatin
• Urea

Topics

• Animals
• Benzyl Compounds (pharmacology)
• Ganglia, Spinal (metabolism)
• Hyperalgesia (chemically induced)
• Male
• Mice
• Organoplatinum Compounds (antagonists & inhibitors, pharmacology)
• Oxaliplatin
• Proto-Oncogene Proteins c-myc (antagonists & inhibitors)
• Skin (metabolism)
• TRPA1 Cation Channel
• TRPM Cation Channels (antagonists & inhibitors, biosynthesis)
• Thiazoles (pharmacology)
• Transient Receptor Potential Channels (antagonists & inhibitors)
• Urea (pharmacology)