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

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 (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 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 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.

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.

• Authors: Ken Masuguchi, Hitomi Watanabe, Takehiro Kawashiri, Soichiro Ushio, Nana Ozawa, Haruka Morita, Ryozo Oishi, Nobuaki Egashira
• Journal: Life sciences (Life Sci) Vol. 98 Issue 1 Pg. 49-54 (Mar 07 2014) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 24412642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Analgesics
• Organoplatinum Compounds
• Polysaccharides
• Receptors, G-Protein-Coupled
• Oxaliplatin
• Serotonin
• neurotropin

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Male
• Neuralgia (chemically induced, drug therapy)
• Organoplatinum Compounds
• Oxaliplatin
• Polysaccharides (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, G-Protein-Coupled (drug effects)
• Serotonin (metabolism)
• Spinal Cord (drug effects, metabolism)