Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan.
Eur J Cancer. 2012 Jun;48(9):1407-13. doi: 10.1016/j.ejca.2011.08.009. Epub 2011 Sep 8.
Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice.
奥沙利铂是治疗结直肠癌的关键药物,但它会导致患者出现急性和慢性周围神经病变。葛根汤(GJG)是一种汉方药,用于治疗包括疼痛和麻木在内的多种神经症状。最近,有报道称 GJG 可预防临床研究中奥沙利铂引起的周围神经病变。然而,迄今为止,尚无实验研究来确定 GJG 对奥沙利铂诱导的神经病变大鼠模型中疼痛行为的影响。此外,其对奥沙利铂的抗肿瘤作用的影响尚不清楚。在本研究中,我们研究了 GJG 对奥沙利铂诱导的周围神经病变和抗肿瘤活性的影响。重复给予奥沙利铂可引起 3 至 37 天的冷超敏反应和 21 至 28 天的机械性痛觉过敏。重复给予 GJG 可预防奥沙利铂引起的冷超敏反应,但不能预防大鼠坐骨神经中的机械性痛觉过敏和轴突变性。GJG 的单次给药可减轻神经病变发展后的冷超敏反应和机械性痛觉过敏。此外,GJG 不影响奥沙利铂在肿瘤细胞或肿瘤细胞植入小鼠中的抗肿瘤作用。这些结果表明,GJG 可缓解奥沙利铂引起的冷超敏反应和机械性痛觉过敏,而不影响奥沙利铂的抗肿瘤活性,因此在临床实践中可能对奥沙利铂引起的周围神经病变有用。