Effects of midazolam in the spinal nerve ligation model of neuropathic pain in rats
Effects of midazolam in the spinal nerve ligation model of neuropathic pain in rats
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DOI：
10.1016/s0304-3959(99)00298-5
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发表时间：
2000-04-01
期刊：
影响因子：
7.4
通讯作者：
Dickenson, AH
中科院分区：
文献类型：
--
作者：
Kontinen, VK;Dickenson, AH
通过比较全身给予苯二氮卓类咪达唑仑对脊神经结扎大鼠和对照动物背角伤害性诱发反应的影响，研究了脊神经损伤后脊髓GABA能活性的潜在变化。在成年雄性Sprague-Dawley大鼠中进行L（5）和L 6脊神经的紧密结扎，并使用von Prey毛发和丙酮跌落试验评估所产生的机械和冷异常性疼痛。手术后15-18天，在氟烷麻醉下，使用三倍于C纤维阈值的经皮电刺激感受野，进行背角神经元的单单位细胞外记录。脊神经结扎组大鼠出现机械痛和冷痛诱发痛，假手术对照组未见。皮下注射咪达唑仑0.1-3.0 mg/kg可降低所有研究组中A δ纤维诱发的活动，且呈剂量相关性，但仅脊神经结扎组中C纤维诱发的活动显著降低。s.c.咪达唑仑可被i.t.给药氟马西尼，表明作用的脊髓部位。咪达唑仑减少C-纤维诱发放电显着更多的脊神经结扎模型比非手术或假手术对照。这些结果表明，在脊髓GABA能系统的神经病理性动物的变化，并可能在神经病理性疼痛的新的治疗方法的发展具有重要意义。(C)2000年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Potential changes in the spinal GABAergic activity after nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal nerve ligation of neuropathy and control animals. The tight ligation of the L(5) and L6 spinal nerves was performed in adult male Sprague-Dawley rats and resulting mechanical and cold allodynia were assessed with von Prey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. The rats in the spinal nerve ligation group, but not in the sham-operated control group developed mechanical and cold allodynia. Subcutaneous administration of midazolam 0.1-3.0 mg/kg reduced the A delta-fibre evoked activity in a dose-related manner in all study groups, but the C-fibre evoked activity was significantly reduced only in the spinal nerve ligation group. The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal nerve ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.