Center of Neuroplasticity and Pain, SMI, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Center of Neuroplasticity and Pain, SMI, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Biophys J. 2019 Jul 23;117(2):281-295. doi: 10.1016/j.bpj.2019.04.041. Epub 2019 Jun 14.
Small-surface-area electrodes have successfully been used to preferentially activate cutaneous nociceptors, unlike conventional large area-electrodes, which preferentially activate large non-nociceptor fibers. Assessments of the strength-duration relationship, threshold electrotonus, and slowly increasing pulse forms have displayed different perception thresholds between large and small surface electrodes, which may indicate different excitability properties of the activated cutaneous nerves. In this study, the origin of the differences in perception thresholds between the two electrodes was investigated. It was hypothesized that different perception thresholds could be explained by the varying distributions of voltage-gated ion channels and by morphological differences between peripheral nerve endings of small and large fibers. A two-part computational model was developed to study activation of peripheral nerve fibers by different cutaneous electrodes. The first part of the model was a finite-element model, which calculated the extracellular field delivered by the cutaneous electrodes. The second part of the model was a detailed multicompartment model of an Aδ-axon as well as an Aβ-axon. The axon models included a wide range of voltage-gated ion channels: Na, Na, Na, K, K, K, and HCN channel. The computational model reproduced the experimentally assessed perception thresholds for the three protocols, the strength-duration relationship, the threshold electrotonus, and the slowly increasing pulse forms. The results support the hypothesis that voltage-gated ion channel distributions and morphology differences between small and large fibers were sufficient to explain the difference in perception thresholds between the two electrodes. In conclusion, assessments of perception thresholds using the three protocols may be an indirect measurement of the membrane excitability, and computational models may have the possibility to link voltage-gated ion channel activation to perception threshold measurements.
小表面积电极已成功用于优先激活皮肤伤害感受器，而不同于常规的大面积电极，后者优先激活大的非伤害感受器纤维。对强度-时间关系、阈电紧张和逐渐增加的脉冲形式的评估显示，大表面积和小表面积电极之间存在不同的感知阈值，这可能表明激活的皮肤神经的兴奋性不同。在这项研究中，研究了两种电极之间感知阈值差异的起源。假设不同的感知阈值可以通过电压门控离子通道的不同分布以及小纤维和大纤维的周围神经末梢的形态差异来解释。开发了一个两部分的计算模型来研究不同皮肤电极对周围神经纤维的激活。该模型的第一部分是一个有限元模型，计算由皮肤电极传递的细胞外场。模型的第二部分是 Aδ-轴突和 Aβ-轴突的详细多腔室模型。轴突模型包括广泛的电压门控离子通道：Na+、Na+、Na+、K+、K+、K+和 HCN 通道。计算模型再现了三种方案的实验评估感知阈值、强度-时间关系、阈电紧张和逐渐增加的脉冲形式。结果支持了这样的假设，即小纤维和大纤维之间的电压门控离子通道分布和形态差异足以解释两种电极之间感知阈值的差异。总之，使用三种方案评估感知阈值可能是对膜兴奋性的间接测量，并且计算模型有可能将电压门控离子通道的激活与感知阈值测量联系起来。
