摘要
背景脊髓灰质背角的甘氨酸能神经元与减轻外周炎症引起的脊髓疼痛和慢性疼痛有关。神经元异构体甘氨酸转运体-2（ClyT2）可重吸收突触前释放的甘氨酸并调节甘氨酸能神经传递。本实验目的即研究甘氨酸转运体-2抑制剂ALX1393鞘内注射对急性疼痛模型大鼠是否有抗伤害性感受作用。方法给雄性SD大鼠鞘内置管，通过甩尾实验、热板实验、爪压实验和甲醛实验评估ALX1393（4μg、20μg以及40μg）鞘内注射对大鼠的热性、机械性和化学性伤害，用旋转实验评估其运动功能影响。结果ALX1393对热性和机械性刺激的抗伤害性感受作用存在剂量依赖性关系。给药后15分钟出现最大效果，明显效果持续约60分钟。给予ALX1393后立即注射士的宁可完全拮抗其抗伤害性感受作用。在甲醛实验中，ALXl393有剂量依赖性的减轻疼痛作用，早期和晚期都有，而晚期效果更明显。与抗伤害性感受作用相反，ALX1393用到40μg对运动功能也没有影响。结论本研究证明了ALX1393对急性疼痛的抗伤害性感受作用。结果提示抑制性神经递质转运体有望成为急性疼痛的治疗靶点，Olyr2选择性抑制剂可能会成为新的治疗药物。
BACKGROUND： Glydnergic neurons in the spinal dorsal horn have been implicated in the inhibition of spinal pain processing in peripheral inflammation and chronic pain states. Neuronal isoform glydne transporter-2 （GlyT2） reuptakes presynaptically released glydne and regulates the glydnergic neurotransmission. In this study, we examined whether a selective GlyT2 inhibitor, ALX1393, elidts an antinodceptive effect in a rat acute pain model. METHODS： Male Sprague- Dawley rats were implanted with a catheter intrathecally. The effects of intrathecal administration of ALX1393 （4, 20, or 40 μg） on thermal, mechanical, and chemical nodception were evaluated by tail flick, hot plate, paw pressure, and formalin tests. Furthermore, to explore whether ALX1393 affects motor function, a rotarod test was performed. RESULTS： ALX1393 exhibited antinodceptive effects on the thermal and mechanical stimulations in a dose-dependent manner. The maximal effect of ALXI393 was observed at 15 rain after administration, and a significant effect lasted for about 60 rain. These antinodceptive effects were reversed completely by strychnine iniected immediately after the administration of ALX1393. In the formalin test, ALXI393 inhibited pain behaviors in a dose-dependent manner, both in the early and late phases, although the influence was greater in the late phase. In contrast to antinodceptive action, ALXI393 did not affect motor function up to 40 txg. CON- CLUSIONS： This study demonstrates the antinodceptive action of ALX1393 on acute pain. These findings suggest that the inhibitory neurotransmitter transporters are promising targets for the treatment of acute pain and that the selective inhibitor of GlyT2 could be a novel therapeutic drug.
出处
《麻醉与镇痛》
2012年第1期51-57,共7页
Anesthesia & Analgesia
