Prevention of oxaliplatin-induced mechanical allodynia and neurodegeneration by neurotropin in the rat model.
Oxaliplatin is a key drug for colorectal cancer, but it causes acute peripheral neuropathy (triggered by cold) and chronic neuropathy (sensory and motor neuropathy) in patients. Neurotropin, a non-protein extract from the inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic pains. In the present study, we investigated the effect of neurotropin on the oxaliplatin-induced neuropathy in rats. Repeated administration of oxaliplatin caused cold hyperalgesia from Day 5 to Day 29 and mechanical allodynia from Day 15 to Day 47. Repeated administration of neurotropin relieved the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and inhibited the oxaliplatin-induced axonal degeneration in rat sciatic nerve. Neurotropin also inhibited the oxaliplatin-induced neurite degeneration in cultured pheochromocytoma 12 (PC12) and rat dorsal root ganglion (DRG) cells. On the other hand, neurotropin did not affect the oxaliplatin-induced cell injury in rat DRG cells. These results suggest that repeated administration of neurotropin relieves the oxaliplatin-induced mechanical allodynia by inhibiting the axonal degeneration and it is useful for the treatment of oxaliplatin-induced neuropathy clinically.
Kawashiri
Takehiro
T
Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Egashira
Nobuaki
N
Watanabe
Hitomi
H
Ikegami
Yoko
Y
Hirakawa
Shingo
S
Mihara
Yuki
Y
Yano
Takahisa
T
Ikesue
Hiroaki
H
Oishi
Ryozo
R
D000096:Acetone; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D016501:Neurites / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010070:Oxalates / Q000494:pharmacology; D000077150:Oxaliplatin; D016716:PC12 Cells; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D011134:Polysaccharides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology
D000700:Analgesics; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010070:Oxalates; D011134:Polysaccharides; D000077150:Oxaliplatin; D000096:Acetone; C010491:neurotropin