Authier Nicolas, Gillet Jean Pierre, Fialip Joseph, Eschalier Alain, Coudore François
Laboratoire de Toxicologie, Facultés de Médecine et Pharmacie, EMI INSERM/UdA 9904, 28 place Henri Dunant, BP 38, 63001, Clermont-Ferrand, France.
Exp Neurol. 2003 Jul;182(1):12-20. doi: 10.1016/s0014-4886(03)00003-7.
We report the assessment of motor and sensory behaviors using an electrophysiologic and an histologic approach, in a rat model of cisplatin peripheral neuropathy. Cisplatin was injected intraperitoneally one (3 mg/ kg), two (2 mg/kg), or three (1 mg/kg) times a week up to a cumulative dose of 15 or 20 mg/kg. With regard to nociceptive signs, we observed mechanical and thermal (cold stimuli) hyperalgesia and allodynia associated with minor motor disorders for the 3 mg/kg dose. Peripheral nerve conduction velocities were decreased in the cisplatin-(3 mg/kg) treated group. In addition, the histologic approach revealed that large axons were more frequently affected than the small ones, and nonmyelinated axons were unaffected. However, even in the most severe cases, myelin sheaths remained within normal limits. This animal model of nociceptive neuropathy would be suitable to study the pathophysiologic mechanisms of neuropathic pain and to test potential neuroprotective agents.
我们报告了在顺铂诱导的周围神经病变大鼠模型中,使用电生理和组织学方法对运动和感觉行为进行的评估。顺铂以每周一次(3毫克/千克)、两次(2毫克/千克)或三次(1毫克/千克)的剂量腹腔注射,累积剂量达15或20毫克/千克。关于伤害性体征,我们观察到,对于3毫克/千克剂量组,出现了机械性和热(冷刺激)痛觉过敏以及伴有轻微运动障碍的感觉异常。顺铂(3毫克/千克)治疗组的周围神经传导速度降低。此外,组织学方法显示,大轴突比小轴突更易受到影响,无髓鞘轴突未受影响。然而,即使在最严重的病例中,髓鞘仍保持在正常范围内。这种伤害性神经病变动物模型将适合用于研究神经性疼痛的病理生理机制以及测试潜在的神经保护剂。