侧脑室注射GT-0198 对坐骨神经慢性压迫性 损伤大鼠的研究

Study on the effect of intracerebroventricular injection of GT-0198 on chronic constriction injury of sciatic nerve in rats

摘要:

目的 观察侧脑室注射选择性甘氨酸转运体-2（GlyT2）抑制剂GT-0198 对大鼠慢性压迫损伤 （CCI）神经病理性疼痛模型的镇痛作用。方法 实验大鼠随机分为正常对照组和CCI 组。CCI 组大鼠进行坐 骨神经压迫性损伤模型复制。采用旋转实验评估正常大鼠的运动功能。采用电子Von Frey 实验、冷板实验和热 痛刺激反应分别评估CCI 大鼠机械、冷和热痛觉过敏。侧脑室注射GT-0198（10、50 和100 μg）后观察其 镇痛作用。结果 正常对照组大鼠侧脑室注射GT-0198 不影响其运动功能。GT-0198 抑制CCI 组大鼠机械和 冷痛觉过敏，并呈剂量依赖性。GT-0198（100 μg）的镇痛作用可被侧脑室注射甘氨酸受体拮抗剂—士的宁（STR） 完全逆转。结论 选择性GlyT2 抑制剂GT-0198 可用于治疗大鼠CCI 神经病理性疼痛，同时不影响运动功能。

Abstract:

Objective To examine the antinociceptive effect of intracerebroventricular injection of the selective glycine transporter 2 (GlyT2) inhibitor GT-0198 on neuropathic pain in experimental rat model. Methods Chronic constriction injury (CCI) to the sciatic nerve was induced in rats. Normal rats were used to assess motor function with the rotarod test. The CCI rats were then used to assess mechanical, cold, and thermal hyperalgesia using the electronic von Frey test, cold plate test, and the plantar test, respectively. GT-0198 (10, 50, and 100 μg) was administered intracerebroventricularly to examine its effect on antinociception. Results Intracerebroventricular administration of GT-0198 in normal rats did not affect motor performance. In the CCI rats, GT-0198 inhibited mechanical and cold hyperalgesia in a dose-dependent manner. The antihyperalgesic effect of GT-0198 (100 μg) was reversed completely by pretreatment with a glycine receptor antagonist Strychnine. Conclusions These results suggest that the selective GlyT2 inhibitor is a promising candidate for the treatment of neuropathic pain without causing motor dysfunction.