• Ken Masuguchi, Hitomi Watanabe, Takehiro Kawashiri, Soichiro Ushio, Nana Ozawa, Haruka Morita, Ryozo Oishi, and Nobuaki Egashira.
• Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
• Life Sci. 2014 Mar 7;98(1):49-54.

AimsOxaliplatin 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 MethodsOxaliplatin (4mg/kg) was administered intraperitoneally twice a week for 4weeks. Cold hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test.Key FindingsRepeated 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 α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a Gi protein inhibitor.SignificanceThese 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.Copyright © 2014 Elsevier Inc. All rights reserved.

26 keywords...

hide…