Involvement of descending monoaminergic systems in antiallodynic effect of goshajinkigan in oxaliplatin-treated mice

Oxaliplatin, a key chemotherapeutic drug, frequently causes peripheral neuropathy accompanied by pain and allodynia. A few recent clinical studies showed that a traditional herbal formulation goshajinkigan (GJG) prevents oxaliplatin-induced neuropathy. In this study, we examined the mechanisms underlying acute antiallodynic activity of GJG in mice with oxaliplatin-induced neuropathy. A single intraperitoneal injection of oxaliplatin (3 mg/kg) induced mechanical allodynia, which peaked at day 10 after injection and subsided almost completely by day 18. On day 10 after oxaliplatin injection, oral administration of GJG (0.3 and 1.0 g/kg, but not 0.1 g/kg) inhibited established mechanical allodynia after oxaliplatin administration. The inhibitory effect peaked 30 min after GJG administration and subsided by 2 h. The antiallodynic activity of GJG was inhibited by intrathecal pretreatment with the catecholaminergic neurotoxin 6-hydroxydopamine (20 μg/site) and the serotonergic neurotoxin 5,7-dihydroxytryptamine (20 μg/site). Administration of GJG (1.0 g/kg) to oxaliplatin-treated mice showed no effect on the levels of noradrenaline, serotonin, 3-methoxy-4-hydroxyphenylglycol (a noradrenaline metabolite), and 5-hydroxyindoleacetic acid (a serotonin metabolite). These results suggest that the descending noradrenergic and serotonergic systems are involved in GJG-mediated inhibition of oxaliplatin-induced mechanical allodynia.