Raymond S A
Anesthesia Research Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Anesth Analg. 1992 Dec;75(6):906-21. doi: 10.1213/00000539-199212000-00008.
Phenomena seen in axons exposed to subblocking doses serve as the basis for interpreting clinical and behavioral observations during onset and recovery of peripheral nerve block. To delineate the changes in excitability and in impulse conduction caused by subblocking concentrations of local anesthetics (LAs) in myelinated peripheral nerve fibers, LAs were applied to excised frog sciatic nerves while impulse conduction was monitored in single axons. For concentrations ranging from 0.01 to 1.2 times the LA concentration needed to block impulse conduction, three measures of susceptibility to LA were made to quantify the action of the drugs on "resting" fibers (firing rates < or = 0.5 Hz): the increase in the threshold for electrical activation of impulses, the increase in conduction latency reflecting the slowing of impulse conduction in the region exposed to LA, and the "critical blocking concentration" of LA just sufficient to prevent impulse conduction in the recorded fiber. Wide interfiber variation in these variables was observed (e.g., for lidocaine, latency increases at block ranged from 66% to 257% of control, blocking concentrations ranged from 0.29 to 1.40 mM), which was not correlated with fiber diameter (as indicated by resting conduction velocity). Mathematical modeling of impulse conduction in fibers exposed to LA demonstrated that the interfiber variation in susceptibility to LA block could result from interfiber differences in the density of sodium and potassium channels. The effects of LA were also studied in active fibers (firing rates > 0.5 Hz). Local anesthetics reversibly inhibited two normally occurring afteroscillations in membrane threshold related to afterpotentials following an impulse. These were "superexcitability," a transient lowering of threshold lasting as long as 1 s, and "depression," a phase of raised threshold peaking within 2-4 s after an impulse and recovering slowly over several minutes. Impulse activity also transiently increased the apparent potency of LAs. Such "use-dependent" increases in threshold and decreases in conduction velocity showed kinetics that were agent specific, lasting 1 s after a burst of impulses for lidocaine and lasting > 10 s for bupivacaine. At low concentrations, within the range of nontoxic plasma concentrations after systemic administration, the predominant actions of LAs on conducting fibers were transient decreases in excitability and conduction velocity in combination with a reduction of intrinsic oscillatory aftereffects of impulse discharge. These effects may degrade decoding of information in discharge patterns without actually blocking conduction of infrequent impulses, suggesting how functional blockade of coordinated movement and perception may occur even without complete blockade of impulse conduction.
在暴露于亚阻滞剂量的轴突中观察到的现象，是解释周围神经阻滞开始和恢复期间临床及行为观察结果的基础。为了描绘有髓鞘的周围神经纤维中亚阻滞浓度的局部麻醉药（LA）所引起的兴奋性和冲动传导的变化，将LA应用于离体的青蛙坐骨神经，同时在单个轴突中监测冲动传导。对于浓度范围为阻断冲动传导所需LA浓度的0.01至1.2倍的情况，对LA的敏感性进行了三项测量，以量化药物对“静息”纤维（放电频率≤0.5Hz）的作用：冲动电激活阈值的增加、反映在暴露于LA区域中冲动传导减慢的传导潜伏期的增加，以及刚好足以阻止记录纤维中冲动传导的LA的“临界阻断浓度”。观察到这些变量在纤维间存在很大差异（例如，对于利多卡因，阻断时潜伏期增加范围为对照的66%至257%，阻断浓度范围为0.29至1.40mM），这与纤维直径（以静息传导速度表示）无关。对暴露于LA的纤维中冲动传导进行数学建模表明，纤维对LA阻断敏感性的纤维间差异可能源于钠通道和钾通道密度的纤维间差异。还在活动纤维（放电频率>0.5Hz）中研究了LA的作用。局部麻醉药可逆地抑制了与冲动后的后电位相关的膜阈值中两种正常出现的后振荡。这些是“超兴奋性”，即阈值短暂降低持续长达1秒，以及“抑制”，即冲动后2 - 4秒内阈值升高达到峰值并在几分钟内缓慢恢复的阶段。冲动活动还短暂增加了LA的表观效力。这种阈值的“使用依赖性”增加和传导速度的降低表现出药物特异性的动力学，利多卡因在一阵冲动后持续1秒，布比卡因持续>10秒。在低浓度下，即在全身给药后的无毒血浆浓度范围内，LA对传导纤维的主要作用是兴奋性和传导速度的短暂降低，同时伴随着冲动放电固有振荡后效应的减少。这些效应可能会破坏放电模式中信息的解码，而实际上不会阻断不频繁冲动的传导，这表明即使没有完全阻断冲动传导，协调运动和感知的功能阻断是如何发生的。
