Área de Farmacología, Nutrición y Bromatología, Dpto. C.C. Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Unidad Asociada CSIC-IQM, High Performance Research Group in Experimental Pharmacology (PHARMAKOM), Alcorcón, Spain.
Área de Farmacología, Nutrición y Bromatología, Dpto. C.C. Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Unidad Asociada CSIC-IQM, High Performance Research Group in Experimental Pharmacology (PHARMAKOM), Alcorcón, Spain.
Life Sci. 2021 Jul 15;277:119397. doi: 10.1016/j.lfs.2021.119397. Epub 2021 Mar 29.
Antitumor agents, as taxanes and platinum compounds, induce peripheral neuropathies which can hamper their use for cancer treatment. The study of chemotherapy-induced neuropathies in humans is difficult because of ethical reasons, differences among administration protocols and intrinsic characteristics of patients. The aim of the present study is to compare the neuropathic signs induced by individual or combined administration of paclitaxel and oxaliplatin.
Oxaliplatin and paclitaxel were administered individually and combined to induce peripheral neuropathy in rats, sensory neuropathic signs were assessed in the hind limbs and orofacial area. The in vitro skin-saphenous nerve preparation was used to record the axonal activity of Aδ sensory neurons.
Animals treated with the combination developed mechanical allodynia in the paws and muscular hyperalgesia in the orofacial area, which was similar to that in animals treated with monotherapy, the latter also developed cold allodynia in the paws. Aδ-fibers of the rats treated with the combination were hyperexcited and presented hypersensitivity to pressure stimulation of the innervated skin, also similar to that recorded in the fibers of the animals treated with monotherapy.
Our work objectively demonstrates that the combination of a platinum compound with a taxane does not worsen the development of sensorial neuropathies in rats, which is an interesting data to take into account when the combination of antitumor drugs is necessary. Co-administration of antitumor drugs is more effective in cancer treatment without increasing the risk of the disabling neuropathic side effects.
紫杉烷类和铂类抗肿瘤药物会引起周围神经病变，从而影响其在癌症治疗中的应用。由于伦理原因、给药方案的差异以及患者固有特征的不同，对人类化疗诱导性神经病的研究较为困难。本研究旨在比较紫杉醇和奥沙利铂单独或联合给药引起的周围神经病变。
奥沙利铂和紫杉醇单独或联合给药诱导大鼠周围神经病，评估后肢和口面区域的感觉神经病变体征。采用离体皮肤-隐神经制备来记录 Aδ感觉神经元的轴突活动。
联合用药组动物的足部出现机械性痛觉过敏，口面区域出现肌肉痛觉过敏，与单药治疗组相似，后者的足部也出现冷觉过敏。联合用药组大鼠的 Aδ纤维过度兴奋，对受神经支配皮肤的压力刺激表现出超敏反应，与单药治疗组纤维记录的情况相似。
我们的工作客观地证明，铂类化合物与紫杉烷类药物联合使用不会加重大鼠感觉神经病变的发展，这是在需要联合使用抗肿瘤药物时需要考虑的一个有趣数据。联合使用抗肿瘤药物在提高癌症治疗效果的同时，不会增加致残性神经副作用的风险。
