Gokin A P, Philip B, Strichartz G R
Department of Anesthesiology, Preoperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Anesthesiology. 2001 Dec;95(6):1441-54. doi: 10.1097/00000542-200112000-00025.
Controversy still surrounds the differential susceptibility of nerve fibers to local anesthetics and its relation to selective functional deficits. In the current study we report features of conduction blockade in different classes of rat sciatic nerve fibers after injection of lidocaine by a percutaneous procedure that closely resembles clinical applications.
In 30 adult male Sprague-Dawley rats (weight, 300-400 g) during general anesthesia, impulses were recorded in different classes of sensory axons (large, Aalpha and beta fibers; small, Adelta myelinated fibers and unmyelinated C fibers) and motor axons (large, Aalpha fibers; small, Agamma myelinated fibers) classified by conduction velocity. The sciatic nerve was stimulated distally, and impulses were recorded from small filaments teased from L4-L5 dorsal (sensory) and ventral (motor) roots sectioned acutely from the spinal cord. Lidocaine at concentration of 0.05-1% was injected percutaneously in 0.1-ml solutions at the sciatic notch. Both tonic (stimulated at 0.5 Hz) and use-dependent (stimulated at 40 Hz for Adelta and Agamma fibers and at 5 Hz for C fibers) impulse inhibitions by lidocaine were assayed.
Minimal effective (threshold) lidocaine concentrations (i.e., to block conduction in 10% of fibers) were, for sensory, 0.03% for Adelta, 0.07% for Aalphabeta, and 0.09-0.1% for C fibers, and for motor, 0.03% for Agamma and 0.05% for Aalpha fibers. The order of fiber susceptibility, ranked by concentrations that gave peak tonic fiber blockade of 50% (IC50s), was Agamma > Adelta = Aalpha > Aalphabeta > C. Faster-conducting C fibers (conduction velocity > 1 m/s) were more susceptible (IC50 = 0.13%) than slower ones (conduction velocity < 1 m/s; IC50 = 0.30%). At 1% lidocaine, all fibers were tonically blocked. Use-dependent effects accounted for only a modest potentiation of block (at a lidocaine concentration of 0.25%) in Adelta and Agamma fibers, and in C fibers phasic stimulation had even smaller effects and sometimes relieved tonic block.
Susceptibility to lidocaine does not strictly follow the "size principle" that smaller (slower) axons are always blocked first. This order of fiber blockade is qualitatively consistent with previous reports of the order of functional deficits in the rat after percutaneous lidocaine, that is, motor = proprioception > nociception, if we assume that motor deficits first arise from conduction failure in Agamma fibers and that nociception relies on C fiber conduction.
神经纤维对局部麻醉药的不同敏感性及其与选择性功能缺陷的关系仍存在争议。在本研究中，我们报告了通过一种与临床应用非常相似的经皮程序注射利多卡因后，不同类别的大鼠坐骨神经纤维传导阻滞的特征。
在30只成年雄性Sprague-Dawley大鼠（体重300 - 400克）全身麻醉期间，记录不同类别的感觉轴突（大的Aα和β纤维；小的有髓鞘的Aδ纤维和无髓鞘的C纤维）和运动轴突（大的Aα纤维；小的有髓鞘的Aγ纤维）的冲动，这些轴突根据传导速度进行分类。坐骨神经在远端受到刺激，从脊髓急性切断的L4 - L5背根（感觉）和腹根（运动）中分离出的细丝上记录冲动。将浓度为0.05 - 1%的利多卡因以0.1毫升溶液经皮注射到坐骨切迹处。测定了利多卡因对强直（以0.5赫兹刺激）和使用依赖性（对Aδ和Aγ纤维以40赫兹刺激，对C纤维以5赫兹刺激）冲动的抑制作用。
最小有效（阈值）利多卡因浓度（即阻断10%纤维传导的浓度），对于感觉纤维，Aδ为0.03%，Aαβ为0.07%，C纤维为0.09 - 0.1%；对于运动纤维，Aγ为0.03%，Aα为0.05%。根据使50%强直纤维阻滞达到峰值的浓度（IC50）排列的纤维敏感性顺序为：Aγ > Aδ = Aα > Aαβ > C。传导速度较快的C纤维（传导速度 > 1米/秒）比传导速度较慢的C纤维（传导速度 < 1米/秒；IC50 = 0.30%）更敏感（IC50 = 0.13%）。在1%利多卡因时，所有纤维均被强直阻滞。使用依赖性效应仅在Aδ和Aγ纤维中对阻滞有适度增强作用（在利多卡因浓度为0.25%时），而在C纤维中，相位刺激的作用更小，有时甚至可缓解强直阻滞。
对利多卡因的敏感性并不严格遵循“大小原则”，即较小（较慢）的轴突总是首先被阻断。如果我们假设运动功能缺陷首先源于Aγ纤维的传导失败，而痛觉依赖于C纤维传导，那么这种纤维阻滞顺序在质量上与先前关于经皮注射利多卡因后大鼠功能缺陷顺序的报道一致，即运动 = 本体感觉 > 痛觉。
