Wolff Matthias, Schnöbel-Ehehalt Rose, Mühling Jörg, Weigand Markus A, Olschewski Andrea
From the Department of Anesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University, Giessen, Germany.
Anesth Analg. 2014 Aug;119(2):463-470. doi: 10.1213/ANE.0000000000000280.
Superficial dorsal horn neurons of the spinal cord receive sensory information from Aδ and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons.
Whole-cell patch-clamp recordings from dorsal horn neurons of Wistar rats were used to study the action of lidocaine on firing properties. To estimate the impact of a blockade of voltage-gated potassium channels by lidocaine (100 μM) on the firing properties of different neurons, the sodium and potassium channel inhibition of lidocaine was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs signed rank test was used throughout.
All 3 types of neurons responded to lidocaine with changes in the shape of their action potentials. The peak amplitude of the single action potentials was decreased (P = 0.031, P = 0.013, and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN, AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P = 0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased after application of lidocaine. In tonically firing neurons, lidocaine reduced the repetitive firing (P = 0.0016), and this effect was mimicked by a combination of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine.
Lidocaine at low concentrations suppresses tonic firing neurons by interacting with voltage-gated potassium channels. The effects on adapting firing neurons can be explained by an interaction with voltage-gated sodium channels. In contrast, the firing pattern of SSN is not affected at the administered concentrations. This different sensitivity to low concentrations of sodium and particularly of potassium channel blockers might represent a novel approach for a differentiated blockade of different spinal dorsal horn neurons.
脊髓浅表背角神经元从Aδ和C纤维接收感觉信息。根据它们对持续去极化的反应，这些细胞可分为3组：紧张性（TFN）、适应性（AFN）和单峰放电（SSN）神经元。在脊髓和全身给予利多卡因期间，这些神经元会接触到不同浓度的局部麻醉药利多卡因。在本研究中，我们探讨了其对感觉神经元兴奋性的影响。
采用Wistar大鼠背角神经元的全细胞膜片钳记录来研究利多卡因对放电特性的作用。为了评估利多卡因（100μM）对电压门控钾通道的阻断对不同神经元放电特性的影响，根据河豚毒素（TTX，10 nM）和四乙铵（10 mM）的作用研究了利多卡因对钠和钾通道的抑制作用。在整个过程中使用Wilcoxon配对符号秩检验进行统计分析。
所有3种类型的神经元对利多卡因的反应都是动作电位形状发生改变。单个动作电位的峰值幅度降低（SSN、AFN和TFN神经元分别为P = 0.031、P = 0.013和P = 0.014），动作电位的持续时间增加（SSN、AFN和TFN神经元分别为P = 0.016、P = 0.032和P = 0.031）。应用利多卡因后，最大正斜率（SSN和AFN分别为P = 0.016和P = 0.0010）和负斜率（SSN、AFN和TFN神经元分别为P = 0.016、P = 0.0025和P = 0.020）降低。在紧张性放电神经元中，利多卡因减少了重复放电（P = 0.0016），TTX和四乙铵的组合模拟了这种作用。在AFN中，TTX模拟了利多卡因的作用。
低浓度的利多卡因通过与电压门控钾通道相互作用抑制紧张性放电神经元。对适应性放电神经元的影响可以通过与电压门控钠通道的相互作用来解释。相比之下，在所给予的浓度下，SSN的放电模式不受影响。对低浓度钠通道阻滞剂尤其是钾通道阻滞剂的这种不同敏感性可能代表了一种对不同脊髓背角神经元进行差异性阻断的新方法。
