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BKCa 通道激动剂NS1619 和Kv通道拮抗剂4-AP对眶下神经慢性缩窄环术大鼠面部机械痛阈的影响

刘蔡钺, 李娜, 赵云富, 马蓓

第二军医大学生理学教研室，上海 200433； 上海长征医院口腔科，上海200003；中国人民解放军第五十九医院麻醉科，开远 661600

摘要

三叉神经痛(trigeminal neuralgia)是临床上的顽疾，长期以来为医学界所重视，但其发病机制尚不清晰，临床上也无有效的治疗方法。本研究首先通过免疫荧光化学法和动物行为学测定，对经眶下孔达三叉神经节目标注射给药法的效果进行了评价，然后行眶下神经慢性缩窄环术(chronic constriction injury of the infraorbital nerve, ION-CCI)建立三叉神经病理性痛大鼠模型，用经眶下孔达三叉神经节目标注射法分别注射BKCa 通道激动剂NS1619 和Kv 通道拮抗剂4-AP，观察药物对大鼠面部机械痛阈的影响。结果显示，通过经眶下孔达三叉神经节目标注射法，药物可以准确到达三叉神经节，并产生了比一般眶下孔注射给药法更为持久的注射效果。ION-CCI 术后第6 天大鼠术侧面部触须垫部产生了显著的异常性疼痛(allodynia)，并可以维持到至少术后第42 天。在ION-CCI 术后第15 天大鼠，运用经眶下孔达三叉神经节目标注射法注射BKCa 通道激动剂NS1619 可以剂量依赖性地显著提高ION-CCI 组大鼠的面部机械痛阈，逆转面部痛觉过敏；而在ION-CCI术后第35 天痛阈部分恢复的大鼠，同样方法注射Kv 通道拮抗剂4-AP 又可以显著降低面部痛阈。以上结果表明，BKCa 通道激动剂NS1619 和Kv 通道拮抗剂4-AP 可以显著影响ION-CCI 大鼠的面部机械痛阈，提示激活BKCa 通道可以抑制由IONCCI引起的三叉神经病理性痛，而激活Kv 通道可能对ION-CCI 引起的三叉神经病理痛有紧张性的抑制作用。

关键词： 眶下神经慢性缩窄环术; 神经病理性痛; 三叉神经节; 目标注射; NS1619 ; 4 -AP

分类号：R331

[BKCa channel agonist NS1619 and Kv channel antagonist 4-AP on the facial mechanical pain threshold in a rat model of chronic constriction injury of the infraorbital nerve.] [Ariticle in Chinese]

LIU Cai-Yue, LI Na, ZHAO Yun-Fu, MA Bei

Department of Physiology, the Second Military Medical University, Shanghai 200433, China； Department of Stomatology, Changzheng Hospital, Shanghai 200003, China； 3Department of Anesthesia, No. 59 Hospital of Chinese People’s Liberation Army, Kaiyuan 661600, China

Abstract

Trigeminal neuralgia is a paroxysmal disorder with severely disabling facial pain and thus continues to be a real therapeuticchallenge. At present there are few effective drugs for treatment of this pain. The present study was aimed to explore the involvementof BKCa channels and Kv channels in the mechanical allodynia in a rat model of trigeminal neuropathic pain. Here the effectiveness ofdrug target injection at the trigeminal ganglion through the infraorbital foramen was first evaluated by immunofluorescence and animalbehavior test. Trigeminal neuropathic pain model was established by chronic constriction injury of the infraorbital nerve (ION-CCI) inrats. BKCa channel agonist and Kv channel antagonist were administered into the trigeminal ganglion in ION-CCI rats and sham rats by the above target injection method, and the facial mechanical pain threshold was measured. The results showed that the drug couldaccurately reach the trigeminal ganglion by target injection which was more effective than that by the normal injection around infraorbitalforamen. Rats suffered significant mechanical allodynia in the whisker pad of the operated side from 6 d to 42 d after ION-CCI.BKCa channel agonist NS1619 significantly and dose-dependently attenuated the facial mechanical allodynia and increased the facialmechanical pain threshold in ION-CCI rats 15 d after operation. Kv antagonist 4-AP was able to reduce the threshold in ION-CCI ratswhen facial mechanical threshold was partly recovered and relatively stable on the 35th day after operation. These results suggest thatBKCa channel agonist NS1619 and Kv channel antagonist 4-AP can significantly affect the rats’ facial mechanical pain threshold afterION-CCI. Activation of BKCa channels may be related to the depression of the primary afferent neurons in trigeminal neuropathic painpathways. Activation of Kv channels may exert a tonic inhibition on the trigeminal neuropathic pain.

Key words: ION-CCI; neuropathic pain; trigeminal ganglion; target injection; NS1619; 4-AP

收稿日期：2010-07-05　　录用日期：2010-08-02

通讯作者：赵云富　　E-mail: zhaoyf1818@126.com

引用本文：

刘蔡钺, 李娜, 赵云富, 马蓓. BKCa 通道激动剂NS1619 和Kv通道拮抗剂4-AP对眶下神经慢性缩窄环术大鼠面部机械痛阈的影响[J]. 生理学报 2010; 62 (5): 441-449.

LIU Cai-Yue, LI Na, ZHAO Yun-Fu, MA Bei. [BKCa channel agonist NS1619 and Kv channel antagonist 4-AP on the facial mechanical pain threshold in a rat model of chronic constriction injury of the infraorbital nerve.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (5): 441-449 (in Chinese with English abstract).