Model-based analysis of subthreshold mechanisms of spinal cord stimulation for pain.
Model-based analysis of subthreshold mechanisms of spinal cord stimulation for pain.
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DOI：
10.1088/1741-2552/ad0858
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发表时间：
2023-11-09
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
目标。脊髓刺激（SCS）是治疗慢性疼痛的常用方法。几十年来，SCS最大化了刺激诱导的感觉异常和患者疼痛区域之间的重叠。最近开发的SCS模式以难以察觉的幅度缓解疼痛，但对这些新波形的神经反应或其镇痛作用机制知之甚少。因此，在这项研究中，我们研究了多种形式的无感觉异常SCS的神经反应。的方法。我们使用计算模型来研究三种无感觉异常的SCS模式（burst， 1khz和10khz SCS）的神经生理效应和普遍提出的机制的合理性。具体而言，在C-和a - β-纤维中，我们研究了不同SCS波形对峰值时间和激活阈值的影响，以及随机离子通道门控如何影响背柱轴突的响应。最后，我们对背浅角神经元的膜极化进行了表征。主要的结果。我们发现没有SCS波形激活或调制c -纤维的尖峰时间。在a - β-纤维中，脉冲时序仅在阈值以上振幅处被调制。离子通道的随机性对a β-纤维的激活阈值影响不大，但在阈值以上的振幅处产生非均匀的峰值时间。最后，局部细胞在轴突末端优先极化，这种极化的大小取决于细胞形态和相对于刺激电极的位置。的意义。总的来说，感觉下SCS的作用机制尚不清楚。我们的研究结果表明，没有SCS波形直接激活c -纤维，并且在阈下振幅下不可能调制峰值时间。我们得出结论，SCS对局部细胞的潜在阈下神经调节作用本质上可能是突触前的，因为轴突在SCS期间优先去极化。
Objective. Spinal cord stimulation (SCS) is a common treatment for chronic pain. For decades, SCS maximized overlap between stimulation-induced paresthesias and the patient’s painful areas. Recently developed SCS paradigms relieve pain at sub-perceptible amplitudes, yet little is known about the neural response to these new waveforms or their analgesic mechanisms of action. Therefore, in this study, we investigated the neural response to multiple forms of paresthesia-free SCS. Approach. We used computational modeling to investigate the neurophysiological effects and the plausibility of commonly proposed mechanisms of three paresthesia-free SCS paradigms: burst, 1 kHz, and 10 kHz SCS. Specifically, in C- and Aβ-fibers, we investigated the effects of different SCS waveforms on spike timing and activation thresholds, as well as how stochastic ion channel gating affects the response of dorsal column axons. Finally, we characterized membrane polarization of superficial dorsal horn neurons. Main results. We found that none of the SCS waveforms activate nor modulate spike timing in C-fibers. Spike timing was modulated in Aβ-fibers only at suprathreshold amplitudes. Ion channel stochasticity had little effect on Aβ-fiber activation thresholds but produced heterogeneous spike timings at suprathreshold amplitudes. Finally, local cells were preferentially polarized in their axon terminals, and the magnitude of this polarization was dependent on cellular morphology and position relative to the stimulation electrodes. Significance. Overall, the mechanisms of action of subparesthetic SCS remain unclear. Our results suggest that no SCS waveforms directly activate C-fibers, and modulation of spike timing is unlikely at subthreshold amplitudes. We conclude that potential subthreshold neuromodulatory effects of SCS on local cells are likely to be presynaptic in nature, as axons are preferentially depolarized during SCS.
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脊髓刺激必须保留本体感受，以使脊髓损伤的人类运动。
影响因子：
25
作者：
Formento E;Minassian K;Wagner F;Mignardot JB;Le Goff-Mignardot CG;Rowald A;Bloch J;Micera S;Capogrosso M;Courtine G
通讯作者：
Courtine G
影响因子：
2.5
作者：
Crosby, Nathan D.;Janik, John J.;Grill, Warren M.
通讯作者：
Grill, Warren M.
影响因子：
8.8
作者：
Lempka, Scott F.;McIntyre, Cameron C.;Machado, Andre G.
通讯作者：
Machado, Andre G.
DOI：
10.1111/ner.13116
发表时间：
2020-07
期刊：
Neuromodulation : journal of the International Neuromodulation Society
影响因子：
--
作者：
Quindlen-Hotek JC;Kent AR;De Anda P;Kartha S;Benison AM;Winkelstein BA
通讯作者：
Winkelstein BA
影响因子：
2.8
作者：
Deer, Timothy;Slavin, Konstantin V.;Wilson, Derron
通讯作者：
Wilson, Derron