Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Eur J Pain. 2011 Apr;15(4):344-50. doi: 10.1016/j.ejpain.2010.08.006. Epub 2010 Sep 9.
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.
奥沙利铂是结直肠癌的关键药物，但它会导致患者出现急性周围神经病变（由冷触发）和慢性神经病变（感觉和运动神经病变）。神经妥乐平是一种从接种牛痘病毒的兔炎性皮肤中提取的非蛋白提取物，已被用于治疗各种慢性疼痛。在本研究中，我们研究了神经妥乐平对奥沙利铂诱导的大鼠神经病变的影响。奥沙利铂重复给药会导致大鼠从第 5 天到第 29 天出现冷超敏反应，从第 15 天到第 47 天出现机械性痛觉过敏。神经妥乐平重复给药可缓解奥沙利铂引起的机械性痛觉过敏，但不能缓解冷超敏反应，并抑制奥沙利铂引起的大鼠坐骨神经轴突变性。神经妥乐平还抑制了奥沙利铂诱导的培养嗜铬细胞瘤 12（PC12）和大鼠背根神经节（DRG）细胞的神经突变性。另一方面，神经妥乐平不影响奥沙利铂诱导的大鼠 DRG 细胞的细胞损伤。这些结果表明，神经妥乐平重复给药通过抑制轴突变性缓解奥沙利铂引起的机械性痛觉过敏，对临床上奥沙利铂诱导的神经病变的治疗有用。
