Uemura Yuhei, Fujita Tsugumi, Ohtsubo Sena, Hirakawa Naomi, Sakaguchi Yoshiro, Kumamoto Eiichi
Department of Physiology, Saga Medical School, Saga 849-8501, Japan ; Department of Anesthesiology & Critical Care Medicine, Saga Medical School, Saga 849-8501, Japan.
Department of Physiology, Saga Medical School, Saga 849-8501, Japan.
Biomed Res Int. 2014;2014:540238. doi: 10.1155/2014/540238. Epub 2014 Feb 24.
Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na(+) and Ca(2+) channels, glutamate-receptor inhibition, and GABA(A)-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine) concentration dependently reduced the peak amplitude of the CAP (IC50 = 0.44 and 0.50 mM, resp.). Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM) reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate) at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50 = 0.23 mM). These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine) as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.
用于治疗神经性疼痛的抗癫痫药物具有多种作用，包括对电压门控性钠（Na⁺）通道和钙（Ca²⁺）通道的作用、谷氨酸受体抑制以及GABA（A）受体激活，而局部麻醉药也用于缓解疼痛。局部麻醉药对神经传导的抑制程度与抗癫痫药物相比有何不同，目前尚未得到充分研究。采用气隙法记录青蛙坐骨神经纤维的快传导复合动作电位（CAPs）。抗癫痫药物（拉莫三嗪和卡马西平）浓度依赖性地降低了CAP的峰值幅度（IC50分别为0.44和0.50 mM）。卡马西平类似物奥卡西平的抑制作用小于卡马西平。抗癫痫药物苯妥英钠（0.1 mM）使CAP幅度降低了15%。另一方面，其他抗癫痫药物（加巴喷丁、丙戊酸钠和托吡酯）在10 mM时对CAPs无影响。CAPs受到局部麻醉药左旋布比卡因的抑制（IC50 = 0.23 mM）。这些结果表明，抗癫痫药物在神经传导抑制程度上存在差异，并且一些抗癫痫药物抑制神经传导的效果与左旋布比卡因或其他局部麻醉药（利多卡因、罗哌卡因和可卡因）相似，如先前报道。这可能有助于了解神经传导抑制在抗癫痫药物抗伤害感受中的作用。
