Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature leads to faster activation of voltage-gated potassium ion channels. The minimum length needed to block an axon scaled with the square root of the axon’s diameter. Significance. The results suggest that voltage-dependent potassium ion channels play a major role in thermal block, and that relatively short lengths of axon could be thermally manipulated to selectively block fine, unmyelinated axons, such as C fibers, that carry pain and other sensory information.

Thermal block of unmyelinated axons may serve as a modality for control, suggesting a means for providing therapies for pain. Computational modeling predicted that potassium channels are necessary for mediating thermal block of propagating compound action potentials (CAPs) with infrared (IR) light. Our study tests that hypothesis. Results suggest that potassium channel blockers disrupt the ability of IR to block propagating CAPs in Aplysia californica nerves, whereas sodium channel blockers appear to have no significant effect. These observations validate the modeling results and suggest potential applications of thermal block to many other unmyelinated axons. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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...

Finite element models (continuum and vascular) were developed that can be used to predict temperature rise and quantify the thermal dose resulting from laser irradiation of excised rat skin samples and live anesthetized mouse tissue. The vascular model incorporating blood perfusion effects predicted temperature rise better in the live animal tissue. The models developed demonstrated that pulsed lasers caused greater temperature rise and delivered a greater thermal dose than CW lasers of equal average power, especially during the initial transients of irradiation. This analysis will be beneficial for thermal therapy applications where maximum delivery of thermal dose over a short period of time is important.

Objective. Infrared neural inhibition (INI) is a method of blocking the generation or propagation of neural action potentials through laser heating with wavelengths strongly absorbed by water. Recent work has identified that the distance heated along axons, the block length (BL), modulates the temperature needed for inhibition; however, this relationship has not been characterized. This study explores how BL during INI can be optimized towards minimizing its temperature threshold. Approach. To understand the relationship between BL and the temperature required for INI, excised nerves from Aplysia californica were laser-heated over different lengths of axon during electrical stimulation of compound action potentials. INI was provided by irradiation (λ = 1470 nm) from a custom probe (n = 6 nerves), and subsequent validation was performed by providing heat block using perfused hot media over nerves (n = 5 nerves). Main Results. Two BL regimes were identified. Short BLs (thermal full width at half maximum (tFWHM) = 0.81–1.13 mm) demonstrated that increasing the tFWHM resulted in lower temperature thresholds for INI (p < 0.0125), while longer BLs (tFWHM = 1.13–3.03 mm) showed no significant change between the temperature threshold and tFWHM (p > 0.0125). Validation of this longer regime was performed using perfused hot media over different lengths of nerves. This secondary heating method similarly showed no significant change (p > 0.025) in the temperature threshold (tFWHM = 1.25–4.42 mm). Significance. This work characterized how the temperature threshold for neural heat block varies with BL and identified an optimal BL around tFWHM = 1.13 mm which minimizes both the maximum temperature applied to tissue and the volume of tissue heated during INI. Understanding how to optimally target lengths of nerve to minimize temperature during INI can help inform the design of devices for longitudinal animal studies and human implementation.