Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat
Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat
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DOI：
10.1016/s1098-7339(06)80010-6
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发表时间：
1997-05-01
期刊：
影响因子：
--
通讯作者：
Yaksh, TL
中科院分区：
文献类型：
--
作者：
Hwang, JH;Yaksh, TL
背景和目标。脊髓γ-氨基丁酸(GABA)受体已被证明对神经损伤后诱发的痛觉异常有调节作用。本研究旨在观察GABA类似物加巴喷丁[1-(氨基甲基)-环己烷乙酸]蛛网膜下腔注射对大鼠神经病理性疼痛模型的止痛作用。方法：研究方法。采用腰蛛网膜下腔置管，结扎L5-6神经根诱导大鼠痛觉过敏(Chung模型)。结果。脊髓注射加巴喷丁对痛觉超敏有剂量依赖性(10-1,000微克)拮抗作用，但对运动功能无明显影响。蛛网膜下腔注射GABAA拮抗剂荷包牡丹碱(0.3mUg)或GABA受体激动剂注射后5min或60min后注射GABA B拮抗剂CGP 35348(30mU G)均不能逆转加巴喷丁的止痛作用。结论。加巴喷丁具有抗痛觉过敏作用，但其作用机制尚不清楚。GABA A或B拮抗剂在逆转各自激动剂作用的剂量下未能逆转这一效应，这表明加巴喷丁通过不涉及GABA A或GABA B位点的机制参与了脊髓系统的调节。
Background and Objectives. Spinal gamma-aminobutyric acid (GABA) receptors have been shown to modulate post-nerve injury-induced allodynia. This study sought to examine the antiallodynic effects of a GABA analog gabapentin [1-(aminomethyl)-cyclohexaneacetic acid], given by subarachnoid injection in a rat neuropathic pain model. Methods. The rats were prepared with lumbar subarachnoid catheters, and allodynia was induced in rats by ligation of the L5-6 nerve roots (Chung model). Results. Spinal injection of gabapentin resulted in a dose-dependent (10-1,000 mu g) antagonism of the allodynia at doses that had no detectable effect on motor function. Subarachnoid injection of either the GABA A antagonist bicuculline (0.3 mu g), or the GABA B antagonist CGP 35348 (30 mu g) 5 minutes before or 60 minutes after injection of GABA receptor agonist did not reverse the antiallodynic effects produced by gabapentin. Conclusions. Gabapentin shows antiallodynic effect, but its mechanism is not known. The failure to reverse this effect by GABA A or B antagonists at doses that reverse the effects of the respective agonists suggests that gabapentin is involved in the modulation of spinal systems by mechanisms that do not involve either a GABA A or a GABA B site.