- 作者：Ken Masuguchi ; Hitomi Watanabe ; Takehiro Kawashiri ; Soichiro Ushio ; Nana Ozawa ; Haruka Morita ; Ryozo Oishi ; Nobuaki Egashira ; n-egashi@pharm.med.kyushu-u.ac.jp" class="auth_mail
- 关键词：Oxaliplatin (PubChem CID ; 5310940) ; Prazosin (PubChem CID ; 4893) ; Yohimbine (PubChem CID ; 8969) ; WAY100635 (PubChem CID ; 5684) ; Ketanserin (PubChem CID ; 3822) ; 6-Hydroxydopamine (PubChem CID ; 4624) ; p-Chlorophenylalanine (PubChem CID ; 26229)
- 刊名：Life Sciences
- 出版年：7 March, 2014
- 年：2014
- 卷：98
- 期：1
- 页码：49-54
- 全文大小：371 K
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-HT1A, 5-HT2, 5-HT3, and 伪2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a Gi 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.