ATP敏感型钾通道调控剂在吗啡抗慢性神经病理性疼痛中的作用

doi:吉林大学青年教师基金资助课题，长春科委社

ATP敏感型钾通道调控剂在吗啡抗慢性神经病理性疼痛中的作用

麻海春¹，2,刁润新¹，韩树海¹，冯春生¹，卢宝顺¹，赵华^2*

1. 吉林大学第一医院麻醉科，吉林长春130021；2. 吉林大学基础医学院生理学教研室，吉林长春130021

收稿日期:2004-03-29 修回日期:1900-01-01 出版日期:2004-11-28 发布日期:2004-11-28
通讯作者: 赵华

Effects of adenosine triphosphate-sensitive potassium channel opener on morphine antinociception during intrathecal administration in rats

MA Hai-chun¹,2,DIAO Run-xin¹，HAN Shu-hai¹， FENG Chun-sheng¹,LU Bao-shun¹, ZHAO Hua^2*

1.Department of Anesthesiology, First Hospital, Jilin University, Changchun 130021, China;2. Department of Physiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China

Received:2004-03-29 Revised:1900-01-01 Online:2004-11-28 Published:2004-11-28
Contact: ZHAO Hua

摘要/Abstract

摘要： 目的:探讨ATP敏感型钾通道(K⁺_ATP)调控剂和电压依赖型钾通道（K⁺_V）调控剂对蛛网膜下腔应用吗啡抗神经病理性疼痛作用的影响。方法:35只SD大鼠，结扎左侧L₅脊神经根建立慢性神经痛模型。3 d后蛛网膜下腔留置PE-10导管。随机每5只SD大鼠为一组于术后第7天经导管蛛网膜下腔分别注射10 μL下列药物: K⁺_ATP通道开放剂尼可的尔(Nic) 5 μg、K⁺_ATP通道抑制剂格列本脲(Gli) 2 μg、K⁺_V通道抑制剂4-氨基吡啶（4-AP）2 μg、吗啡(Mor) 5 μg、Nic 5 μg+Mor 5 μg、Gli 2 μg+Mor 5 μg、4-AP 2 μg+Mor 5 μg或等量盐水(Sal)。注药后20 min，用热平板法测量大鼠后爪的热痛敏阈值。采用最大效应百分比（%MPE）表示热痛敏阈值。结果:术后第7天左侧L₅脊神经结扎大鼠后肢痛阈较未结扎侧对照组（右侧）大鼠后肢痛阈明显降低（P<0.01）。蛛网膜下腔单独注射K⁺_ATP通道开放剂Nic、K⁺_ATP通道抑制剂Gli、 K⁺_V通道抑制剂4-AP及Sal不影响神经病理性疼痛大鼠的痛阈，Nic(K⁺_ATP)增强Mor镇痛效果提高痛阈，Gli(K⁺_ATP) 抑制Mor镇痛效果降低痛阈，而4-AP（K⁺_V）对Mor镇痛效果无影响。结论:在脊髓水平K⁺_ATP通道调节Mor对慢性神经病理性疼痛大鼠的镇痛作用。

关键词: 格列本脲, 4-氨基吡啶, 神经痛, 蛛网膜下腔, 吗啡, 钾通道, 药理作用

Abstract: Objective To investigate the effects of adenosine triphosphate-sensitive potassium (K⁺_ATP) channel opener nicorandil (Nic), K⁺_ATP inhibitor glibenclamide (Gli) and voltage gated potassium (K⁺_V) channel inhibitor 4-aminopyridine (4-AP) on the morphine (Mor) antinociception during intrathecal administration in rats. Methods Chronic neuropathic model was set up by ligation of left L₅ spinal nerve of Sprague-Dawley rat. Three days later rat was implanted catheter (PE-10) intrathecally. The thermal nociceptive threshold was determined by measuring the withdrawal latency of hindpaw placed on a 58℃ hot plate 7 days after operation. Results Pain threshold of rat′s left hindpaw of ligature group measured by heat stimulation was significantly lowered than that in control group 7 days after operation (P<0.01). The intrathecal administration of Nic 5 μg, Gli 2 μg, 4-AP 2 μg and saline alone did not produce any antinociceptive action, but Nic 5 μg did potentiate the antinociceptive effect induced by intrathecal morphine, and Gli 2 μg abolished the antinociceptive effect induced by intrathecal morphine (P<0.05), whereas 4-AP did not affect the analgesia of morphine. Conclusion K⁺_ATP channels can regulate the analgesic actions of morphine at the spinal cord level.

Key words: gliburide, 4-aminopyridine, neuralgia, subarachnoid space, morphine, potassium channels, drug effects

中图分类号:

R996

麻海春，2,刁润新，韩树海，冯春生，卢宝顺，赵华. ATP敏感型钾通道调控剂在吗啡抗慢性神经病理性疼痛中的作用[J]. J4, 2004, 30(6): 938-940.

MA Hai-chun,2,DIAO Run-xin，HAN Shu-hai， FENG Chun-sheng,LU Bao-shun, ZHAO Hua. Effects of adenosine triphosphate-sensitive potassium channel opener on morphine antinociception during intrathecal administration in rats[J]. J4, 2004, 30(6): 938-940.

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