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.

Keywords: 6-Hydroxydopamine (PubChem CID: 4624); Allodynia; G(i) protein-coupled receptors; Ketanserin (PubChem CID: 3822); Monoamine; Neurotropin; Oxaliplatin; Oxaliplatin (PubChem CID: 5310940); Prazosin (PubChem CID: 4893); WAY100635 (PubChem CID: 5684); Yohimbine (PubChem CID: 8969); p-Chlorophenylalanine (PubChem CID: 26229).