Infrared neural inhibition (INI) is a relatively new modality of neural control which has potential as a novel pain therapy due to its high spatial specificity and selective inhibition of small diameter neurons at lower temperatures. Computational modeling using a modified Hodgkin-Huxley model in the squid giant axon has shown that temperature sensitive potassium currents mediate INI’s thermal block. This model was modified to reflect Aplysia parameters which have smaller unmyelinated axons on the order of mammalian C fibers, and simulated results were validated in vitro. Results support he hypothesis that potassium currents are needed to create a thermal block.
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.
Neuromodulation has the potential to treat various diseases (i.e., heart failure, obesity). Several clinical trials have recently failed because of the inability to modulate small-diameter fibers. Previously, we demonstrated preferential inhibition of small-diameter fibers using infrared neuromodulation (IRN). To understand the mechanism of action, we did a mathematical analysis which suggested that any modality acting primarily on the axonal surface would preferentially affect small-diameter axons. To test our hypothesis, we examined whether isotonic glucose solution would give results similar to IRN.
We stimulated the left and right pleural-abdominal connective nerves of Aplysia californica and recorded the resulting compound action potentials (CAPs). We designed a chamber with three isolated compartments through which the nerve passes sequentially. Aplysia saline is perfused in the two outer chambers while the middle chamber can be perfused with either Aplysia saline or an isotonic glucose solution (10.21 w/v %). The width of the middle chamber is adjustable to vary the length of nerve perfused by the isotonic glucose solution. As the length of the middle chamber increases, recorded CAPs are initially unaffected, then show a loss of peaks representing small-diameter axons, then show no activity. We can restore full, unchanged CAPs by washing out the glucose solution and replacing it with Aplysia saline. These results support the hypothesis that any modality (e.g., both IRN and isotonic glucose solution) acting primarily on the axonal surface would preferentially affect small-diameter axons. Future studies will compare IRN with isotonic glucose block.
Infrared lasers (λ=1.87 μm) are capable of inducing a thermally mediated nerve block in Aplysia and rat nerves. While
this block is spatially precise and reversible in sensory and motor neurons, the mechanism of block is not clearly
understood. Model predictions show that, at elevated temperatures, the rates of opening and closing of the voltage gated
ion channels are disrupted and normal functioning of the gates is hindered. A model combining NEURON with Python is
presented here that can simulate the behavior of unmyelinated nerve axons in the presence of spatially and temporally
varying temperature distributions. Axon behavior and underlying mechanism leading to conduction block is investigated.
The ability to understand the photothermal interaction of laser light and temperature dependence of membrane ion
channels in-silico will help speed explorations of parameter space and guide future experiments testing the feasibility of
selectively blocking pain conduction fibers (Photonic Analgesia of Nerves (PAIN)) in humans.
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