Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

Bhadra, Niloy; Vrabec, Tina; Bhadra, Narendra; Kilgore, Kevin L.

doi:10.2217/bem-2017-0004

Cited by 23 publications

(23 citation statements)

References 66 publications

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“…It is known that application of both high‐frequency alternating current (AC) and direct current (DC) can block neural conduction. It has been shown that high‐frequency AC can preferentially target either larger or smaller diameter axons depending on the frequency used , whereas DC stimulation preferentially blocks large diameter and myelinated neurons first . Specificity in the electrical modulation of neurons has been boosted by using focused multipolar and tripolar stimulation methods .…”

Section: Discussionmentioning

confidence: 99%

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition

et al. 2019

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Background and Objectives The objective of this study is to assess the hypothesis that the length of axon heated, defined here as block length (BL), affects the temperature required for thermal inhibition of action potential propagation applied using laser heating. The presence of such a phenomenon has implications for how this technique, called infrared neural inhibition (INI), may be applied in a clinically safe manner since it suggests that temperatures required for therapy may be reduced through the proper spatial application of light. Here, we validate the presence of this phenomenon by assessing how the peak temperatures during INI are reduced when two different BLs are applied using irradiation from either one or two adjacent optical fibers. Study Design/Materials and Methods Assessment of the role of BL was carried out over two phases. First, a computational proof of concept was performed in the neural conduction simulation environment, NEURON, simulating the response of action potentials to increased temperatures applied at different full‐width at half‐maxima (FWHM) along axons. Second, ex vivo validation of these predictions was performed by measuring the radiant exposure, peak temperature rise, and FWHM of heat distributions associated with INI from one or two adjacent optical fibers. Electrophysiological assessment of radiant exposures at inhibition threshold were carried out in ex vivo Aplysia californica (sea slug) pleural abdominal nerves ( n = 6), an invertebrate with unmyelinated axons. Measurement of the maximum temperature rise required for induced heat block was performed in a water bath using a fine wire thermocouple. Finally, magnetic resonance thermometry (MRT) was performed on a nerve immersed in saline to assess the elevated temperature distribution at these radiant exposures. Results Computational modeling in NEURON provided a theoretical proof of concept that the BL is an important factor contributing to the peak temperature required during neural heat block, predicting a 11.7% reduction in temperature rise when the FWHM along an axon is increased by 42.9%. Experimental validation showed that, when using two adjacent fibers instead of one, a 38.5 ± 2.2% (mean ± standard error of the mean) reduction in radiant exposure per pulse per fiber threshold at the fiber output (P = 7.3E−6) is measured, resulting in a reduction in peak temperature rise under each fiber of 23.5 ± 2.1% ( P = 9.3E−5) and 15.0 ± 2.4% ( P = 1.4E−3) and an increase in the FWHM of heating by 37.7 ± 6.4% ( P = 1E−3), 68.4 ± 5.2% ( P = 2.4E−5), and 51.9 ± 9.9% ( P = 1.7E−3) in three MRT slices. Conclusions This study provides the first experimental evidence for a phenomenon during the heat block in which the temperature for inhibition is dependent on the BL. While more work is needed to further reduce the temperature during INI, the results highlight that spatial application of the temperature rise during INI must be considered. Optimized implementation of INI may leverage this cellular response to provide optical modul...

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Section: Discussionmentioning

confidence: 99%

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition

et al. 2019

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“…Methods to block propagating APs using electrical stimulation are a more recent discovery and a current topic of investigation. Many of the current methods being used or investigated can be effective include the following: Direct current (DC) block [ 3 , 4 , 5 ], kilohertz frequency alternating current block (KHFACb) [ 6 , 7 , 8 , 9 ], anodal block [ 10 , 11 , 12 ], collision block [ 13 ], and quasi-trapezoidal stimulation [ 14 , 15 , 16 , 17 ]. Although translation to clinical use is forthcoming some methods have associated drawbacks that need resolution before translation.…”

Section: Introductionmentioning

confidence: 99%

A Reversible Low Frequency Alternating Current Nerve Conduction Block Applied to Mammalian Autonomic Nerves

Muzquiz

Mintch

Horn

et al. 2021

Sensors

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Electrical stimulation can be used to modulate activity within the nervous system in one of two modes: (1) Activation, where activity is added to the neural signalling pathways, or (2) Block, where activity in the nerve is reduced or eliminated. In principle, electrical nerve conduction block has many attractive properties compared to pharmaceutical or surgical interventions. These include reversibility, localization, and tunability for nerve caliber and type. However, methods to effect electrical nerve block are relatively new. Some methods can have associated drawbacks, such as the need for large currents, the production of irreversible chemical byproducts, and onset responses. These can lead to irreversible nerve damage or undesirable neural responses. In the present study we describe a novel low frequency alternating current blocking waveform (LFACb) and measure its efficacy to reversibly block the bradycardic effect elicited by vagal stimulation in anaesthetised rat model. The waveform is a sinusoidal, zero mean(charge balanced), current waveform presented at 1 Hz to bipolar electrodes. Standard pulse stimulation was delivered through Pt-Black coated PtIr bipolar hook electrodes to evoke bradycardia. The conditioning LFAC waveform was presented either through a set of CorTec® bipolar cuff electrodes with Amplicoat® coated Pt contacts, or a second set of Pt Black coated PtIr hook electrodes. The conditioning electrodes were placed caudal to the pulse stimulation hook electrodes. Block of bradycardic effect was assessed by quantifying changes in heart rate during the stimulation stages of LFAC alone, LFAC-and-vagal, and vagal alone. The LFAC achieved 86.2±11.1% and 84.3±4.6% block using hook (N = 7) and cuff (N = 5) electrodes, respectively, at current levels less than 110 µAp (current to peak). The potential across the LFAC delivering electrodes were continuously monitored to verify that the blocking effect was immediately reversed upon discontinuing the LFAC. Thus, LFACb produced a high degree of nerve block at current levels comparable to pulse stimulation amplitudes to activate nerves, resulting in a measurable functional change of a biomarker in the mammalian nervous system.

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“…Blocking the conduction of activity in peripheral nerves has the potential to alleviate disease symptoms [1][2][3][4]. Kilohertz frequency alternating current (KHFAC) stimulation is an effective method for producing a rapid, controlled, and locally-acting conduction block [4][5][6][7][8]. KHFAC nerve block is quickly reversible, and thus enables both temporal and spatial control of the target tissue with minimal side effects.…”

Section: Introductionmentioning

confidence: 99%

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

Grill

2020

PLoS Comput Biol

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The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na + channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.

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Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

Cited by 23 publications

References 66 publications

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition

Identifying the Role of Block Length in Neural Heat Block to Reduce Temperatures During Infrared Neural Inhibition

A Reversible Low Frequency Alternating Current Nerve Conduction Block Applied to Mammalian Autonomic Nerves

Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

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