From the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Anesth Analg. 2018 Apr;126(4):1381-1392. doi: 10.1213/ANE.0000000000002665.
Local anesthetics have been used clinically for more than a century, but new insights into their mechanisms of action and their interaction with biological systems continue to surprise researchers and clinicians alike. Next to their classic action on voltage-gated sodium channels, local anesthetics interact with calcium, potassium, and hyperpolarization-gated ion channels, ligand-gated channels, and G protein-coupled receptors. They activate numerous downstream pathways in neurons, and affect the structure and function of many types of membranes. Local anesthetics must traverse several tissue barriers to reach their site of action on neuronal membranes. In particular, the perineurium is a major rate-limiting step. Allergy to local anesthetics is rare, while the variation in individual patient's response to local anesthetics is probably larger than previously assumed. Several adjuncts are available to prolong sensory block, but these typically also prolong motor block. The 2 main research avenues being followed to improve action of local anesthetics are to prolong duration of block, by slow-release formulations and on-demand release, and to develop compounds and combinations that elicit a nociception-selective blockade.
局部麻醉药在临床上已经使用了一个多世纪，但它们的作用机制及其与生物系统的相互作用的新见解仍令研究人员和临床医生感到惊讶。除了对电压门控钠离子通道的经典作用外，局部麻醉药还与钙、钾和超极化门控离子通道、配体门控通道和 G 蛋白偶联受体相互作用。它们在神经元中激活许多下游途径，并影响多种类型膜的结构和功能。局部麻醉药必须穿过几个组织屏障才能到达其在神经元膜上的作用部位。特别是神经外膜是一个主要的限速步骤。局部麻醉药过敏很少见，而个体患者对局部麻醉药的反应差异可能比以前认为的要大。有几种辅助方法可延长感觉阻滞，但这些方法通常也会延长运动阻滞。目前正在研究两种主要方法来改善局部麻醉药的作用，一种是通过缓慢释放制剂和按需释放来延长阻滞持续时间，另一种是开发出能引起伤害感受选择性阻滞的化合物和组合。
