TY - JOUR
T1 - Involvement of descending monoaminergic systems in antiallodynic effect of goshajinkigan in oxaliplatin-treated mice
AU - Kitamura, Ryo
AU - Andoh, Tsugunobu
AU - Fushimi, Hirotoshi
AU - Komatsu, Katsuko
AU - Shibahara, Naotoshi
AU - Kuraishi, Yasushi
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - descending noradrenergic system
KW - descending serotonergic system
KW - goshajinkigan
KW - mechanical allodynia
KW - oxaliplatin
UR - http://www.scopus.com/inward/record.url?scp=85009429616&partnerID=8YFLogxK
U2 - 10.11339/jtm.30.183
DO - 10.11339/jtm.30.183
M3 - 学術論文
AN - SCOPUS:85009429616
SN - 1880-1447
VL - 30
SP - 183
EP - 189
JO - Journal of Traditional Medicines
JF - Journal of Traditional Medicines
IS - 4
ER -