High-frequency stimulation induces axonal conduction block without generating initial action potentials

Zhong, Yihua; Wang, Jicheng; Beckel, Jonathan M.; Groat, William C. de; Tai, Changfeng

doi:10.1007/s10827-021-00806-4

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…However, when HFBS is applied for a long period, a post-stimulation block can occur as revealed by this (figures 2(A) and (B)) and previous modeling studies [10,18] as well as animal studies [7][8][9]. The post-stimulation block is due to the increase in intracellular sodium concentration by a long-duration HFBS as revealed by previous modeling studies [10,18]. Therefore, the question becomes which mechanism is playing the role in axonal conduction block immediately before terminating a long-duration HFBS.…”

Section: Discussionsupporting

confidence: 69%

“…This acute block is due to HFBSinduced membrane potential oscillation that opens the potassium channel constantly and eliminates the delay between sodium and potassium current generation during a depolarization, thereby preventing the generation of an AP [11,12]. However, when HFBS is applied for a long period, a post-stimulation block can occur as revealed by this (figures 2(A) and (B)) and previous modeling studies [10,18] as well as animal studies [7][8][9]. The post-stimulation block is due to the increase in intracellular sodium concentration by a long-duration HFBS as revealed by previous modeling studies [10,18].…”

Section: Discussionsupporting

confidence: 57%

“…If the intensity can be reduced from 5.4 mA to 4.6 mA as shown in this study, this could save about 13% battery power of a chronically implanted stimulator thereby extending the life of the implant or the time interval for electrical charging. Furthermore, recent model analysis [18] has shown that by adaptively stepwise increasing the HFBS intensity the initial nerve firing produced by HFBS can be eliminated, which is beneficial in clinical applications to block chronic pain of peripheral origin [3]. Once the HFBS intensity is increased to a level that produces nerve block, this could be followed by a linear reduction as suggested by this study to reach a final HFBS intensity to maintain the nerve block for a longer time.…”

Section: Discussionmentioning

confidence: 74%

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Intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency biphasic stimulation

Zhong¹,

Zhang²,

Beckel³

et al. 2022

J. Neural Eng.

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Objective. A new axonal conduction model was used to analyze the interaction between intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency (kHz) biphasic stimulation (HFBS). Approach. The model includes intracellular and extracellular sodium and potassium concentrations and ion pumps. First, the HFBS (1 kHz, 5.4 mA) was applied for a duration (59.4 seconds) long enough to produce an axonal conduction block after terminating the stimulation, i.e., a post-stimulation block. Then, the intensity of HFBS was reduced to a lower level for 4 seconds to determine if the axonal conduction block could be maintained. Main results. The block duration was shortened from 1363 ms to 5 ms as the reduced HFBS intensity was increased from 0 mA to 4.1 mA. The block was maintained for the entire tested period (4000 ms) if the reduced intensity was above 4.2 mA. At the low intensity (<4.2 mA) the membrane potential oscillation disrupted the post-stimulation block caused by the increased intracellular sodium concentration, while at the high intensity (>4.2 mA) the membrane potential oscillation was strong enough to maintain the block and further increased the intracellular sodium concentration. Significance. This study indicates a possibility to develop a new nerve block method to reduce the HFBS intensity, which can extend the battery life for an implantable nerve stimulator in clinical applications to block pain of peripheral origin.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 74%

See 1 more Smart Citation

Intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency biphasic stimulation

Zhong¹,

Zhang²,

Beckel³

et al. 2022

J. Neural Eng.

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“…Therefore, the improvements seen with KHFAC could be due to blocking of pressure-sensitive Aβ somatosensory neurons that typically carry non-nociceptive signals. Alternatively, some studies indicate that longer application of sub-threshold KHFAC stimulation may be able to block conduction in smaller diameter axons by changing ion concentrations rather than inducing depolarization (Zhong et al 2021 ; Zhong et al May 2022 ). A robust conduction block was not observed at end point.…”

Section: Discussionmentioning

confidence: 99%

High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy

et al. 2023

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Background The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG). Methods To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo., n = 18) were separated into 3 groups: NP injury + KHFAC stimulation (n = 7), NP injury + sham cuff (n = 6), and sham injury + sham cuff (n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated. Results KHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline (p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05). Conclusions KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.

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Pudendal Nerve Block by Adaptively Stepwise Increasing the Intensity of High-Frequency (10 kHz) Biphasic Stimulation

Jian¹,

Wang²,

Shen³

et al. 2023

Neuromodulation: Technology at the Neural Interface

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High-frequency stimulation induces axonal conduction block without generating initial action potentials

Cited by 4 publications

References 25 publications

Intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency biphasic stimulation

Intracellular sodium concentration and membrane potential oscillation in axonal conduction block induced by high-frequency biphasic stimulation

High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy

Pudendal Nerve Block by Adaptively Stepwise Increasing the Intensity of High-Frequency (10 kHz) Biphasic Stimulation

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