The antiallodynic action target of intrathecal gabapentin:: Ca2+ channels, KATP channels or N-methyl-D-aspartic acid receptors?
The antiallodynic action target of intrathecal gabapentin:: Ca2+ channels, KATP channels or N-methyl-D-aspartic acid receptors?
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DOI：
10.1213/01.ane.0000189550.97536.83
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发表时间：
2006-01-01
影响因子：
5.7
通讯作者：
Chiou, LC
中科院分区：
文献类型：
--
作者：
Cheng, JK;Chen, CC;Chiou, LC
加巴喷丁是一种新型镇痛药，其作用机制尚不清楚。我们在术后疼痛模型中研究了鞘内加巴喷丁的抗异常性疼痛作用是否涉及三磷酸腺苷（ATP）敏感性K+（K-ATP）通道、N-甲基-D-天冬氨酸（NMDA）受体和Ca 2+通道。在异氟烷麻醉的大鼠中通过爪切口诱导机械性异常性疼痛。在切口前后和鞘内给药后测量切口部位附近对von Frey细丝刺激的退缩阈值。加巴喷丁（100 μ g）的抗异常性疼痛作用不受鞘内K-ATP通道、NMDA受体或γ-氨基丁酸（GABA）受体拮抗剂预处理的影响。K-ATP通道开放剂和GABA受体激动剂本身对切口后痛觉超敏反应的影响不大。N-型钙通道阻滞剂（ω-芋螺毒素GVIA，0.1-3 μ g），但P/Q-型（ω-蛇毒素IVA）、L-型（维拉帕米、地尔硫卓或尼莫地平）或T-型（米贝拉地尔）钙通道阻滞剂，如加巴喷丁一样，可减轻切口诱导的异常性疼痛。L-型钙通道激活剂Bay K 8644可减弱加巴喷丁和ω-芋螺毒素GVIA的抗触诱发痛作用。这些结果为鞘内注射加巴喷丁的抗异常性疼痛作用可能与N型Ca ~（2+）通道有关，而与K-ATP通道、NMDA或GABA（A）受体无关。
Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)sensitive K+ (K-ATP) channels, N-methyl-D-aspartic acid (NMDA) receptors, and Ca2+ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before and after incision and after intrathecal drug administration. The antiallodynic effect of gabapentin (100 mu g) was not affected by intrathecal pretreatment with antagonists of K-ATP channels, NMDA receptors or gamma-aminobutyric acid (GABA), receptors. K-ATP channel openers and GABA, receptor agonist, per se, had little effect on the postincision allodynic response. The Ca2+ channel blocker of N-type (omega-conotoxin GVIA, 0.1-3 mu g), but not of P/Q-type (omega-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and omega-conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca2+ channel activator. These results provide correlative evidence to support the contention that N-type Ca2+ channels, but not K-ATP channels or NMDA or GABA(A) receptors, might be involved in the antiallodynic effect of intrathecal gabapentin.