Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system

Ken Masuguchi, Hitomi Watanabe, Takehiro Kawashiri, Soichiro Ushio, Nana Ozawa, Haruka Morita, Ryozo Oishi, Nobuaki Egashira

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Aims Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. Main methods Oxaliplatin (4 mg/kg) was administered intraperitoneally twice a week for 4 weeks. Cold hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test. Key findings Repeated injection of oxaliplatin induced cold hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT 1A, 5-HT2, 5-HT3, and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a G i protein inhibitor. Significance These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.

Original languageEnglish
Pages (from-to)49-54
Number of pages6
JournalLife Sciences
Volume98
Issue number1
DOIs
Publication statusPublished - Mar 7 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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