Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA; School of Biomedical Engineering, Capital Medical University, Beijing, China.
Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA.
Neuromodulation. 2023 Apr;26(3):577-588. doi: 10.1111/ner.13501. Epub 2022 Feb 15.
To reveal the possible mechanisms underlying poststimulation block induced by high-frequency biphasic stimulation (HFBS).
A new axonal conduction model is developed for unmyelinated axons. This new model is different from the classical axonal conduction model by including both ion concentrations and membrane ion pumps to allow analysis of axonal responses to long-duration stimulation. Using the new model, the post-HFBS block phenomenon reported in animal studies is simulated and analyzed for a wide range of stimulation frequencies (100 Hz-10 kHz).
HFBS can significantly change the Na and K concentrations inside and outside the axon to produce a post-HFBS block of either short-duration (<500 msec) or long-duration (>3 sec) depending on the duration of HFBS. The short-duration block is due to the fast recovery of the Na and K concentrations outside the axon in periaxonal space by diffusion of ions into and from the large extracellular space, while the long-duration block is due to the slow restoration of the normal Na concentration inside the axon by membrane ion pumps. The 100 Hz HFBS requires the minimal electrical energy to achieve the post-HFBS block, while the 10 kHz stimulation is the least effective frequency requiring high intensity and long duration to achieve the block.
This study reveals two possible ionic mechanisms underlying post-HFBS block of axonal conduction. Understanding these mechanisms is important for improving clinical applications of HFBS block and for developing new nerve block methods employing HFBS.
揭示高频双相刺激(HFBS)后刺激阻滞的可能机制。
为无髓鞘轴突开发了一种新的轴突传导模型。该新模型通过包括离子浓度和膜离子泵来与经典轴突传导模型不同,从而允许分析轴突对长时间刺激的反应。使用新模型,模拟并分析了动物研究中报道的 HFBS 后阻滞现象,刺激频率范围很广(100 Hz-10 kHz)。
HFBS 可显著改变轴突内外的 Na 和 K 浓度,从而产生 HFBS 后短时间(<500 msec)或长时间(>3 sec)阻滞,具体取决于 HFBS 的持续时间。短时间阻滞是由于离子通过扩散进出大细胞外空间,使轴突周围的 Na 和 K 浓度在短时间内快速恢复,而长时间阻滞是由于膜离子泵缓慢恢复轴突内正常的 Na 浓度所致。100 Hz 的 HFBS 以最小的电能实现 HFBS 后阻滞,而 10 kHz 的刺激是最无效的频率,需要高强度和长时间才能实现阻滞。
本研究揭示了 HFBS 后轴突传导阻滞的两种可能离子机制。了解这些机制对于改善 HFBS 阻滞的临床应用以及开发利用 HFBS 的新型神经阻滞方法很重要。