Novel surface electrode design for preferential activation of cutaneous nociceptors.

Objective.Small area electrodes enable preferential activation of nociceptive fibers. It is debated, however, whether co-activation of large fibers still occurs for the existing electrode designs. Moreover, existing electrodes are limited to low stimulation intensities, for which behavioral and physiological responses may be considered less reliable. A recent optimization study showed that there is a potential for improving electrode performance and increase the range of possible stimulation intensities. Based on those results, the present study introduces and tests a novel planar concentric array electrode design for small fiber activation in healthy volunteers.Approach.Volunteers received electrical stimulation with the planar concentric array electrode and a regular patch electrode. Perception thresholds (PT) were estimated at the beginning and the end of the experiment. Evoked cortical potentials were recorded in blocks of 30 stimuli. For the patch, stimulation current intensity was set to two times PT, while three intensities, two, five, and ten times PT, were applied with the planar concentric array electrode. Sensation quality, numerical-rating scores, and reaction times were obtained for each PT estimation and during each block of evoked potential recordings.Main results.Stimulation with the patch electrode was characterized as dull, while stimulation with the planar concentric array electrode was characterized as sharp, with increased sharpness for increasing stimulus current intensity. Likewise, scores of the numerical rating scale were higher for the planar concentric array electrode compared to the patch and increased with increasing stimulation current intensity. Reaction times and ERP latencies were longer for the planar concentric array electrode compared to the patch.Significance.The presented novel planar concentric array electrode is a small, non-invasive, and single-use electrode that has the potential to investigate small fiber neuropathy and pain mechanisms, as it is small fiber preferential for a wide range of stimulation intensities.

Increased preferential activation of small cutaneous nerve fibers by optimization of electrode design parameters.

Objective.Electrical preferential activation of small nociceptive fibers may be achieved with the use of specialized small area electrodes, however, the existing electrodes are limited to low stimulation intensities. As existing electrodes have been developed empirically, the present study aimed to use computational modeling and optimization techniques to investigate if changes in electrode design parameters could improve the preferential activation of small fibers.Approach.Two finite element models; one of a planar concentric and one of an intra-epidermal electrode were combined with two multi-compartmental nerve fiber models of an Aδ-fiber and an Aß-fiber. These two-step hybrid models were used for the optimization of four electrode parameters; anode area, anode-cathode distance, cathode area, and cathode protrusion. Optimization was performed using a gradient-free bounded Nelder-Mead algorithm, to maximize the current activation threshold ratio between the Aß-fiber model and the Aδ-fiber model.Main results.All electrode parameters were optimal at their lower bound, except the cathode protrusion, which was optimal a few micrometers above the location of the Aδ-fiber model. A small cathode area is essential for producing a high current density in the epidermal skin layer enabling activation of small fibers, while a small anode area and anode-cathode distance are important for the minimization of current spread to deeper tissues, making it less likely to activate large fibers. Combining each of the optimized electrode parameters improved the preferential activation of small fibers in comparison to existing electrodes, by increasing the activation threshold ratio between the two nerve fiber types. The maximum increase in the activation threshold ratio was 289% and 595% for the intra-epidermal and planar concentric design, respectively.Significance.The present study showed that electrical preferential small fiber activation can be improved by electrode design. Additionally, the results may be used for the production of an electrode that could potentially be used for clinical assessment of small fiber neuropathy.

Comparison of existing electrode designs for preferential activation of cutaneous nociceptors.

OBJECTIVE: Over the recent years, several small area electrodes have been introduced as tools for preferential stimulation of small cutaneous nerve fibers. However, the performance of the electrodes is highly debated and have not previously been systematically compared. The electrodes have been developed empirically and little is known about the electrical potential they produce in the skin, and how this influences the nerve fiber activation. The objective of the present study was to develop and validate a computational model to compare the preferential stimulation of small fibers for electrodes of different designs. APPROACH: A finite element model of the skin was developed and coupled with an Aß-fiber and an Aδ-fiber multi-compartmental nerve fiber model, to describe the current spread and consequent nerve fiber activation produced by five different surface electrodes; intra-epidermal, planar concentric, pin, planar array, and patch. The model was validated through experimental assessments of the strength-duration relationship, impedance, and reaction times. MAIN RESULTS: The computational model predicted the intra-epidermal electrode to be the most preferential for small fiber activation. The intra-epidermal electrode was, however, also found to be the most sensitive to positioning relative to nerve fiber location, which may limit the practical use of the electrode. SIGNIFICANCE: The present study highlights the influence of different electrode design features on the current spread and resulting activation of cutaneous nerve fibers. Additionally, the computational model may be used for the optimization of electrode design towards even better preferential stimulation of small fibers.

From Perception Threshold to Ion Channels-A Computational Study.

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 Aß-axon. The axon models included a wide range of voltage-gated ion channels: NaTTXs, NaTTXr, Nap, Kdr, KM, KA, 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.