Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice
Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice
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DOI：
10.1016/s0014-2999(01)00985-2
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发表时间：
2001-05-11
影响因子：
5
通讯作者：
Kisara, K
中科院分区：
文献类型：
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作者：
Murakami, M;Nakagawasai, O;Kisara, K
我们研究了在小鼠中作用于L-和N-型电压依赖性Ca 2+通道（VDCCs）的二氢吡啶衍生物-在福尔马林试验的后期，鞘内注射NH 4Cl（300 nmol/kg）可显著缩短舔体时间，而另一种二氢吡啶衍生物尼卡地平（300 nmol/kg）则无此作用。西尼地平和ω-芋螺毒素GVIA在相同的实验条件下也显示出显著的镇痛作用。聚合酶链反应（PCR）检测到背根神经节中的α（1A）、α（1B）、α（1 E）、α（1F）、α（1H）、β 3和β 4亚基的转录本，表明存在多种电压依赖性Ca 2+通道。电生理学实验表明，在背根神经节细胞中的N-型电流抑制，曲马多和西尼地平。这些结果表明，多巴胺、西尼地平和ω-芋螺毒素GVIA通过阻断初级伤害性传入纤维中的N型Ca 2+通道发挥其抗伤害性作用。阻断Ca 2+通道导致伤害性感受神经元的突触传递减弱。此外。提示某些N-型钙通道阻滞剂直接应用于蛛网膜下腔时可能具有作为镇痛药的治疗潜力。(C)2001 Elsevier Science B. V.保留所有权利。
We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and omega -conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of alpha (1A), alpha (1B), alpha (1E), alpha (1F), alpha (1H), beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and omega -conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore. it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space. (C) 2001 Elsevier Science B.V. All rights reserved.