Department of Anaesthesiology and Pain Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Gu, Seoul, Republic of Korea.
Br J Anaesth. 2012 Dec;109(6):968-74. doi: 10.1093/bja/aes306. Epub 2012 Aug 30.
Carbamazepine and pregabalin have proven effects against neuropathic pain. Carbamazepine blocks voltage-dependent Na(+) channels, whereas pregabalin blocks voltage-dependent Ca(2+) channels. The authors hypothesized that the co-administration of these drugs would synergistically reduce neuropathic pain.
Neuropathic pain was induced by L5 nerve ligation in Sprague-Dawley rats. To determine their ED(50) values, carbamazepine and pregabalin were orally administered at 0.3, 3, 10, or 30 mg kg(-1). The drugs were then co-administered at 0, 1/4×ED(50), 1/2×ED(50), 1.5×ED(50), and 2×ED(50) to determine the ED(50) and ED(75) values of the drugs in combination. Allodynia was determined using the von Frey hair test and dose-effect curves and isobolograms were used to investigate drug interactions. Levels of the acute reactive protein c-Fos in the dorsal horn were evaluated as an indicator of pathological nerve excitation.
At ED(50) levels, carbamazepine and pregabalin did not exhibit synergism, but doses higher than ED(75) were found to be synergistic. The combination index was 0.18 (strong synergy) and dose reductions were 35.7-fold for carbamazepine and 6.8-fold for pregabalin when co-administered when compared with a single administration at ED(75). The percentage allodynia relief was only 60% for carbamazepine and 80% for pregabalin by single administration, whereas their co-administration relieved allodynia by 100%. Furthermore, treatment decreased c-Fos expression in the dorsal horn, but expressional differences between animals treated with carbamazepine plus pregabalin were not significantly different from those treated with single drug.
Carbamazepine and pregabalin ameliorate neuropathic pain synergistically at higher doses.
卡马西平和普瑞巴林已被证明可有效治疗神经性疼痛。卡马西平可阻断电压依赖性钠通道，而普瑞巴林则阻断电压依赖性钙通道。作者推测，这两种药物联合使用可协同减轻神经性疼痛。
通过 L5 神经结扎诱导 Sprague-Dawley 大鼠产生神经性疼痛。为确定其 ED50 值，分别给予卡马西平和普瑞巴林 0.3、3、10 或 30 mg/kg 口服。然后，在 0、1/4×ED50、1/2×ED50、1.5×ED50 和 2×ED50 时联合给予这些药物，以确定药物联合使用的 ED50 和 ED75 值。使用 Von Frey 毛发试验确定痛觉过敏，并绘制剂量-效应曲线和等效应线以研究药物相互作用。评估背角中急性反应蛋白 c-Fos 的水平，作为病理性神经兴奋的指标。
在 ED50 水平，卡马西平和普瑞巴林未表现出协同作用，但高于 ED75 的剂量则表现出协同作用。联合指数为 0.18（强协同），与 ED75 时单药相比，联合用药时卡马西平的剂量减少了 35.7 倍，普瑞巴林的剂量减少了 6.8 倍。卡马西平单药治疗的痛觉过敏缓解率仅为 60%，普瑞巴林为 80%，而两者联合用药可完全缓解痛觉过敏。此外，治疗还降低了背角中 c-Fos 的表达，但卡马西平联合普瑞巴林治疗与单药治疗的动物之间的表达差异无统计学意义。
卡马西平和普瑞巴林在较高剂量时协同改善神经性疼痛。
