Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia
Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia
复制标题
钠通道亚型在局部麻醉中的具体作用的表征
DOI：
10.1097/aap.0000000000000294
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发表时间：
2015
影响因子：
5.1
通讯作者：
Liu Jin
中科院分区：
文献类型：
--
作者：
Wang Xiaojia;Zhou Cheng;Liang Peng;Yang Jun;Li Fengshan;Liao Daqing;Huang Han;Liu Jin
背景和目的常用的局麻药（如利多卡因）对钠通道亚型的阻滞是非选择性的，可能导致不良事件，如长期的肌肉麻痹和血流动力学不稳定。亚型选择性钠通道阻滞可能避免这些不必要的不良反应，同时保留理想的麻醉效果。钠通道亚型在区域麻醉不同成分中的作用尚不清楚，本研究假设选择性钠通道亚型阻滞可能产生选择性神经阻滞。方法采用利多卡因（非选择性钠通道阻滞剂）、河豚毒素（TTX，TTX敏感性钠通道阻滞剂）和A-803467（选择性Nav1.8亚型阻滞剂）对小鼠坐骨神经进行阻滞。注射研究药物后，评价触觉感觉、针刺和热感觉阻滞以及运动阻滞。测定利多卡因、TTX和A-803467的半数有效浓度（EC 50）及其阻滞持续时间。结果利多卡因产生的局部麻醉效应包括触觉、针刺、热感觉和运动阻滞，其EC 50分别为4.4（3.7-5.2）、9.4（8.0-10.9）、5.2（4.3-6.2）和3.7（3.3-4.2）mmol/L。河豚毒素产生触觉感觉阻滞和运动阻滞，EC 50（平均值，95% CI）分别为7.7（6.0-11.0）和8.3（7.4-9.8）mol/L;而A-803467仅产生触觉感觉阻滞，EC 50（平均值，95% CI）为12.6（11.7-15.6）mol/L。结论钠通道亚型选择性阻滞剂可产生选择性神经阻滞。河豚毒素敏感性钠通道亚型有助于低阈值感觉阻滞（例如，触觉）和运动阻滞。出乎意料的是，选择性Nav1.8亚型阻滞诱导低阈值感觉阻滞，而不是伤害性或运动阻滞。
Background and Objectives Commonly used local anesthetics (eg, lidocaine) are nonselective in blocking sodium channel subtypes, potentially resulting in adverse events, such as prolonged muscle paralysis and unstable hemodynamics. Subtype-selective sodium channel block might avoid these unwanted adverse effects while preserving desirable anesthetic effects. The contributions of sodium channel subtypes in different components of regional anesthesia are unclear and this study assumed that selective sodium channel subtype block might produce selective nerve block. Methods Sciatic nerve block was performed in mice with lidocaine (nonselective sodium channel blocker), tetrodotoxin (TTX, TTX-sensitive sodium channel blocker), and A-803467 (selective Nav1.8 subtype blocker). Tactile sensory, pinprick, and thermal sensory block as well as motor block were evaluated after injection of study drugs. Median effective concentration (EC50) of lidocaine, TTX, and A-803467 as well as their blocking durations were determined. Results Lidocaine produced regional anesthetic effects including tactile, pinprick, and thermal sensory block as well as motor block, with EC50 [mean, 95% confidence intervals (CIs)] of 4.4 (3.7–5.2), 9.4 (8.0–10.9), 5.2 (4.3–6.2), and 3.7 (3.3–4.2) mmol/L, respectively. Tetrodotoxin produced tactile sensory block and motor block with EC50 (mean, 95% CIs) of 7.7 (6.0–11.0) and 8.3 (7.4–9.8) &mgr;mol/L, respectively; whereas A-803467 produced tactile sensory block only, with EC50 (mean, 95% CIs) of 12.6 (11.7–15.6) &mgr;mol/L. Conclusions Sodium channel subtype selective blockers could induce selective nerve blocks. Tetrodotoxin-sensitive sodium channel subtypes contribute to low-threshold sensory block (eg, tactile) and motor block. Unexpectedly, selective Nav1.8 subtype block induced low-threshold sensory block rather than nociceptive or motor block.