Behavioral and electrophysiological studies in rats with cisplatin-induced chemoneuropathy
Behavioral and electrophysiological studies in rats with cisplatin-induced chemoneuropathy
复制标题
DOI：
10.1016/j.brainres.2008.07.022
复制
发表时间：
2008-09-16
期刊：
影响因子：
2.9
通讯作者：
Dougherty, Patrick M.
中科院分区：
文献类型：
--
作者：
Cata, Juan P.;Weng, Han-Rong;Dougherty, Patrick M.
神经病变是与主要类别的一线癌症治疗药物相关的主要剂量限制性副作用。在这里，大鼠皮肤的机械和热刺激的行为反应的变化与顺铂治疗后发生的脊髓神经生理学的变化，伴随着化疗引起的痛觉过敏的发展进行了探讨。顺铂的全身治疗诱导了Sprague-Dawley大鼠的机械和热皮肤感觉撤回阈值的变化。高剂量化疗产生痛觉减退，而低剂量产生痛觉过敏。在化疗诱导的痛觉过敏大鼠的后续神经生理学研究表明，深脊髓板宽动态范围神经元有显着更高的自发活动和更长的后放电伤害性机械刺激比对照组大鼠的宽动态范围神经元;顺铂给药也与更长的后放电和异常的发条经皮电刺激。在顺铂诱导的痛觉过敏期间观察到的超兴奋性与在用其他非常不同类型的化疗剂治疗后产生的痛觉过敏大鼠中观察到的超兴奋性非常相似，并且与在特定类型的直接神经损伤后观察到的超兴奋性相似。(c)2008 Elsevier B. V.保留所有权利。
Neuropathy is the chief dose-limiting side effect associated with the major classes of frontline cancer therapy drugs. Here the changes in behavioral responses of rats to cutaneous mechanical and thermal stimuli occurring following treatment with cisplatin and the changes in spinal neurophysiology accompanying the development of chemotherapy-induced hyperalgesia were explored. Systemic treatment with cisplatin induced changes in both mechanical and thermal cutaneous sensory withdrawal thresholds of Sprague-Dawley rats. High doses of chemotherapy produced hypoalgesia whereas lower doses produced hyperalgesia. Follow-up neurophysiological studies in rats with chemotherapy-induced hyperalgesia revealed that deep spinal lamina wide dynamic range neurons had significantly higher spontaneous activity and longer afterdischarges to noxious mechanical stimuli than wide dynamic range neurons in control rats; cisplatin administration was also associated with longer afterdischarges and abnormal wind-up to transcutaneous electrical stimuli. The hyperexcitability observed during cisplatin-induced hyperalgesia is very similar to that observed in rats with hyperalgesia produced following treatment with other very diverse types of chemotherapeutic agents and similar to that observed following specific types of direct nerve injury. (c) 2008 Elsevier B.V. All rights reserved.