Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Neuromodulation. 2021 Jun;24(4):655-671. doi: 10.1111/ner.13211. Epub 2020 Jun 24.
Dorsal root ganglion stimulation (DRGS) is an effective therapy for chronic pain, though its mechanisms of action are unknown. Currently, we do not understand how clinically controllable parameters (e.g., electrode position, stimulus pulse width) affect the direct neural response to DRGS. Therefore, the goal of this study was to utilize a computational modeling approach to characterize how varying clinically controllable parameters changed neural activation profiles during DRGS.
We coupled a finite element model of a human L5 DRG to multicompartment models of primary sensory neurons (i.e., Aα-, Aβ-, Aδ-, and C-neurons). We calculated the stimulation amplitudes necessary to elicit one or more action potentials in each neuron, and examined how neural activation profiles were affected by varying clinically controllable parameters.
In general, DRGS predominantly activated large myelinated Aα- and Aβ-neurons. Shifting the electrode more than 2 mm away from the ganglion abolished most DRGS-induced neural activation. Increasing the stimulus pulse width to 500 μs or greater increased the number of activated Aδ-neurons, while shorter pulse widths typically only activated Aα- and Aβ-neurons. Placing a cathode near a nerve root, or an anode near the ganglion body, maximized Aβ-mechanoreceptor activation. Guarded active contact configurations did not activate more Aβ-mechanoreceptors than conventional bipolar configurations.
Our results suggest that DRGS applied with stimulation parameters within typical clinical ranges predominantly activates Aβ-mechanoreceptors. In general, varying clinically controllable parameters affects the number of Aβ-mechanoreceptors activated, although longer pulse widths can increase Aδ-neuron activation. Our data support several Neuromodulation Appropriateness Consensus Committee guidelines on the clinical implementation of DRGS.
背根神经节刺激(DRGS)是一种有效的慢性疼痛治疗方法,但作用机制尚不清楚。目前,我们不了解临床可控制参数(例如,电极位置、刺激脉冲宽度)如何影响对 DRGS 的直接神经反应。因此,本研究的目的是利用计算建模方法来描述在 DRGS 过程中,改变临床可控制参数如何改变神经激活谱。
我们将人体 L5 背根神经节的有限元模型与初级感觉神经元(即 Aα-、Aβ-、Aδ-和 C-神经元)的多室模型耦合。我们计算了引起每个神经元一个或多个动作电位所需的刺激幅度,并研究了改变临床可控制参数如何影响神经激活谱。
一般来说,DRGS 主要激活大的有髓 Aα-和 Aβ-神经元。将电极从神经节移开超过 2mm 会消除大部分 DRGS 诱导的神经激活。将刺激脉冲宽度增加到 500μs 或更长时间会增加激活的 Aδ-神经元数量,而较短的脉冲宽度通常仅激活 Aα-和 Aβ-神经元。将阴极放置在神经根附近,或阳极放置在神经节体附近,可最大限度地激活 Aβ-机械感受器。有保护的活动接触配置不会比传统的双极配置激活更多的 Aβ-机械感受器。
我们的结果表明,在典型临床范围内使用刺激参数进行的 DRGS 主要激活 Aβ-机械感受器。一般来说,改变临床可控制参数会影响激活的 Aβ-机械感受器数量,尽管较长的脉冲宽度可以增加 Aδ-神经元的激活。我们的数据支持一些神经调节适宜性共识委员会关于 DRGS 临床实施的指南。