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

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)49-54
ページ数6
ジャーナルLife Sciences
98
発行部数1
DOI
出版物ステータス出版済み - 3 7 2014

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oxaliplatin
Hyperalgesia
Pain
Analgesics
Proteins
Rats
Receptors, Serotonin, 5-HT3
Spinal Injections
neurotropin
Pertussis Toxin
Peripheral Nervous System Diseases
Acetone

All Science Journal Classification (ASJC) codes

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

これを引用

Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system. / Masuguchi, Ken; Watanabe, Hitomi; kawashiri, takehiro; Ushio, Soichiro; Ozawa, Nana; Morita, Haruka; Oishi, Ryozo; Egashira, Nobuaki.

:: Life Sciences, 巻 98, 番号 1, 07.03.2014, p. 49-54.

研究成果: ジャーナルへの寄稿記事

Masuguchi, Ken ; Watanabe, Hitomi ; kawashiri, takehiro ; Ushio, Soichiro ; Ozawa, Nana ; Morita, Haruka ; Oishi, Ryozo ; Egashira, Nobuaki. / Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system. :: Life Sciences. 2014 ; 巻 98, 番号 1. pp. 49-54.
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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.",
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AB - 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.

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