Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Anesth Analg. 2011 Oct;113(4):947-50. doi: 10.1213/ANE.0b013e3182283486. Epub 2011 Jul 7.
The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy in humans. Rodent models to investigate mechanisms and treatments are largely restricted to male rats, whereas female mouse studies are lacking. We characterized a range of paclitaxel doses on cold and mechanical allodynia in male and female C57Bl/6 mice. Because the nonpsychoactive phytocannabinoid cannabidiol attenuates other forms of neuropathic pain, we assessed its effect on paclitaxel-induced allodynia. Paclitaxel produced allodynia that was largely dose independent and more robust in female mice, and this effect was prevented by treatment with cannabidiol. Our preliminary findings therefore indicate that cannabidiol may prevent the development of paclitaxel-induced allodynia in mice and therefore be effective at preventing dose-limiting paclitaxel-induced peripheral neuropathy in humans.
紫杉醇是一种常用的化疗药物,常引起人类外周神经病变。用于研究其发病机制和治疗方法的啮齿类动物模型主要局限于雄性大鼠,而缺乏雌性小鼠的研究。我们描述了一系列紫杉醇剂量对雄性和雌性 C57Bl/6 小鼠冷觉过敏和机械性痛觉过敏的影响。由于非精神活性植物大麻素大麻二酚可减轻其他类型的神经病理性疼痛,我们评估了其对紫杉醇诱导的痛觉过敏的作用。紫杉醇引起的痛觉过敏在雌性小鼠中更为明显,且基本与剂量无关,这种作用可被大麻二酚治疗所预防。因此,我们的初步发现表明,大麻二酚可能预防紫杉醇诱导的痛觉过敏在小鼠中的发展,因此可能对预防人类中剂量限制的紫杉醇诱导的外周神经病变有效。