High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief
High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief
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DOI：
10.1111/ner.12436
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发表时间：
2016-06-01
期刊：
影响因子：
2.8
通讯作者：
Shils, Jay L.
中科院分区：
文献类型：
--
作者：
Arle, Jeffrey E.;Mei, Longzhi;Shils, Jay L.
目的：脊髓刺激（SCS）通过逆行刺激背柱轴突及其对宽动态范围（WDR）神经元的抑制作用来治疗神经性疼痛。典型的 SCS 使用 50-100 Hz 的频率。较新的刺激范例使用高达 10 kHz 的高频刺激 (HFS)，可缓解疼痛，但不会出现感觉异常。我们的假设是，基于离子通道门的动力学和沿轴突看到的电势梯度，HFS 优先阻断较大直径的轴突 (12-15 μm)，从而抑制 WDR 细胞而不会出现感觉异常。方法：我们将 SCS 有限元模型中的场电势值输入到活动轴突模型中，该模型具有纤维直径为 1-20 μm 的离子通道子组件，并在 0.001 毫秒时间尺度上模拟动力学。结果：假设在轴突处看到一定程度的波整流，动作电位 (AP) 阻断如假设的那样发生，优先在较大直径而不是较小直径中发生，而大多数中型和大直径的阻断发生在 4.5 至 10 kHz 之间。模拟显示离子通道门和虚拟阳极动力学都是必要的。结论：在临床 HFS 频率和脉冲宽度下，HFS 优先阻挡较大直径的纤维，同时招募中型和较小的纤维。这些效应是离子门动力学和源自轴突上电流分布的“激活功能”(AF) 之间相互作用的结果。在低频模拟中引起感觉异常的较大纤维被阻断，而中等和较小的纤维被招募，通过抑制 WDR 细胞来缓解无感觉异常的神经性疼痛。
Objective: Spinal cord stimulation (SCS) treats neuropathic pain through retrograde stimulation of dorsal column axons and their inhibitory effects on wide dynamic range (WDR) neurons. Typical SCS uses frequencies from 50-100 Hz. Newer stimulation paradigms use high-frequency stimulation (HFS) up to 10 kHz and produce pain relief but without paresthesia. Our hypothesis is that HFS preferentially blocks larger diameter axons (12-15 mu m) based on dynamics of ion channel gates and the electric potential gradient seen along the axon, resulting in inhibition of WDR cells without paresthesia.Methods: We input field potential values from a finite element model of SCS into an active axon model with ion channel sub-components for fiber diameters 1-20 mu m and simulated dynamics on a 0.001 msec time scale.Results: Assuming some degree of wave rectification seen at the axon, action potential (AP) blockade occurs as hypothesized, preferentially in larger over smaller diameters with blockade in most medium and large diameters occurring between 4.5 and 10 kHz. Simulations show both ion channel gate and virtual anode dynamics are necessary.Conclusion: At clinical HFS frequencies and pulse widths, HFS preferentially blocks larger-diameter fibers and concomitantly recruits medium and smaller fibers. These effects are a result of interaction between ion gate dynamics and the "activating function" (AF) deriving from current distribution over the axon. The larger fibers that cause paresthesia in low-frequency simulation are blocked, while medium and smaller fibers are recruited, leading to paresthesia-free neuropathic pain relief by inhibiting WDR cells.