Alternating current and infrared produce an onset-free reversible nerve block

Lothet, Emilie H.; Kilgore, Kevin L.; Bhadra, Niloy; Vrabec, Tina; Wang, Yves T.; Jansen, E. Duco; Jenkins, Michael W.; Chiel, Hillel J.

doi:10.1117/1.nph.1.1.011010

Cited by 31 publications

(24 citation statements)

References 14 publications

(16 reference statements)

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“…We hypothesize that more complex irradiation schemes that utilize INI's size principle and BL phenomena along with the ability to focus light to a small spot will provide more targeted inhibition of specific neural populations, and this can be used for providing targeted therapy. Further, INI and electrical inhibition may be implemented synergistically, as was demonstrated by Lothet et al [18], and as was demonstrated during neural excitation by Duke et al [41,63].…”

Section: Targeting Neural Subpopulationsmentioning

confidence: 80%

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: Targeting Neural Subpopulationsmentioning

confidence: 80%

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

et al. 2019

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“…Previous studies have shown heatbased inhibitions in unmyelinated/thinly myelinated fibers (Wang et al, 1999;Chow et al, 2009;Rojas and Gonzalez-Lima, 2011;Yan et al, 2011;Duke et al, 2013;Kingsley et al, 2014;Lothet et al, 2014Lothet et al, , 2017. Moreover, increase in body temperature in patients with demyelination disorders results in inhibition of these fibers and exacerbation of symptoms (Wang et al, 1999;Frohman et al, 2011).…”

Section: Discussionmentioning

confidence: 95%

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

2019

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A group of vestibular afferent nerve fibers with irregular-firing resting discharges are thought to play a prominent role in responses to fast head movements and vestibular plasticity. We show that, in C57BL/6 mice (either sex, 4-5 weeks old), normal activity in the efferent vestibular pathway is required for function of these irregular afferents. Thermal inhibition of efferent fibers results in a profound inhibition of irregular afferents' resting discharges, rendering them inadequate for signaling head movements. In this way, efferent inputs adjust the contribution of the peripheral irregular afferent pathway that plays a critical role in peripheral vestibular signaling and plasticity.

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“…The effect of KHFAC modulation lasted for 20 min and caused no permanent nerve damage, as indicated by a full recovery of ventilation and hypoxic responses to pre-KHFAC values at 1 week after cessation of KHFAC modulation. The 'onset response', a transitory endorgan activation that commonly occurs at 10 kHz (and below) in motor nerves [31,32], was evident as an enhanced cardiorespiratory response at 20 kHz modulation of the CSN, less evident at 30 kHz and not observed at 50 kHz. Also, the stress response to 9 week KHFAC modulation of the CSN at 50 kHz with a 2 mA current was minimal, as assessed by corticosterone plasma levels.…”

Section: Discussionmentioning

confidence: 99%

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

Sacramento

Chew²,

Melo

et al. 2018

Diabetologia

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Aims/hypothesis A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function. Herein we characterise the ability of a novel bioelectronic application, classified as kilohertz frequency alternating current (KHFAC) modulation, to suppress neural signals within the CSN of rodents. Methods Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60% lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces were bilaterally implanted in the CSNs and attached to an external pulse generator. The rats were then randomised to KHFAC or sham modulation groups. KHFAC modulation variables were defined acutely by respiratory and cardiac responses to hypoxia (10% O 2 + 90% N 2 ). Insulin sensitivity was evaluated periodically through an ITT and glucose tolerance by an OGTT. Results KHFAC modulation of the CSN, applied over 9 weeks, restored insulin sensitivity (constant of the insulin tolerance test [K ITT ] HFHSu sham, 2.56 ± 0.41% glucose/min; K ITT HFHSu KHFAC, 5.01 ± 0.52% glucose/min) and glucose tolerance (AUC HFHSu sham, 1278 ± 20.36 mmol/l × min; AUC HFHSu KHFAC, 1054.15 ± 62.64 mmol/l × min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin resistance and glucose intolerance returned to normal values within 5 weeks. Conclusions/interpretation KHFAC modulation of the CSN improves metabolic control in rat models of type 2 diabetes. These positive outcomes have significant translational potential as a novel therapeutic modality for the purpose of treating metabolic diseases in humans.

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Alternating current and infrared produce an onset-free reversible nerve block

Cited by 31 publications

References 14 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

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

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