Preferential activation of small cutaneous fibers through small pin electrode also depends on the shape of a long duration electrical current

Abstract

Background Electrical stimulation is widely used in experimental pain research but it lacks selectivity towards small nociceptive fibers. When using standard surface patch electrodes and rectangular pulses, large fibers are activated at a lower threshold than small fibers. Pin electrodes have been designed for overcoming this problem by providing a higher current density in the upper epidermis where the small nociceptive fibers mainly terminate. At perception threshold level, pin electrode stimuli are rather selectively activating small nerve fibers and are perceived as painful, but for high current intensity, which is usually needed to evoke sufficient pain levels, large fibers are likely co-activated. Long duration current has been shown to elevate the threshold of large fibers by the mechanism of accommodation. However, it remains unclear whether the mechanism of accommodation in large fibers can be utilized to activate small fibers even more selectively by combining pin electrode stimulation with a long duration pulse. Results In this study, perception thresholds were determined for a patch- and a pin electrode for different pulse shapes of long duration. The perception threshold ratio between the two different electrodes was calculated to estimate the ability of the pulse shapes to preferentially activate small fibers. The perception threshold ratios were compared between stimulation pulses of 5- and 50 ms durations and shapes of: exponential increase, linear increase, bounded exponential, and rectangular. Qualitative pain perception was evaluated for all pulse shapes delivered at 10 times perception threshold. The results showed a higher perception threshold ratio for long duration 50 ms pulses than for 5 ms pulses. The highest perception threshold ratio was found for the 50 ms, bounded exponential pulse shape. Results furthermore revealed different strength-duration relation between the bounded exponential- and rectangular pulse shapes. Pin electrode stimulation at high intensity was mainly described as “stabbing”, “shooting”, and “sharp”. Conclusion These results indicate that long duration pulses with a bounded exponential increase preferentially activate the small nociceptive fibers with a pin electrode and concurrently cause elevated threshold of large non-nociceptive fibers with patch electrodes.

Comparison of existing electrode designs for preferential activation of cutaneous nociceptors

“…The computational model predicted the nerve fiber activation ratio to increase with increasing pulse length, which is in agreement with the results of Hugosdottir et al [52] and Jonas et al [53], who showed that long duration current stimulation was able to increase the perception threshold ratio of the patch and pin electrodes. The ratio did not only increase for longer stimuli, but also for pulse shapes with a slow rise time [52]. This approach takes advantage of the differences in voltage gated ion channel distribution between nerve fiber types [21], and the phenomenon of accommodation for large fibers.…”

Spinal spatial integration of nociception and its functional role assessed via the nociceptive withdrawal reflex and psychophysical measures in healthy humans

“…Last, regarding the observed quality of the perception, the descriptor most commonly chosen for single stimulation was Sharp, while for double stimulation, the most frequently selected descriptor was Stabbing (Figure 9). For both types of stimulations, the use of small diameter electrodes appeared to evoke a sensation indicative of high proportion of Aδ-fiber activation, as it was expected (Beissner et al, 2010;Frahm et al, 2013;Hugosdottir et al, 2019;Mørch et al, 2011).…”

“…Area‐ and distance‐based spatial summation of perceived intensities are also expected to be observed (Quevedo & Coghill, 2009; Reid et al., 2015). It is also predicted that the use of small diameter electrodes facilitates the stimulation of Aδ‐fibers which will lead to a sharp‐pricking perception quality (Beissner et al., 2010; Hugosdottir et al., 2019; Leandri et al., 2018; Mørch et al., 2011; Torebjörk & Hallin, 1973). Finally, increased IEDs are expected to enhance the spatial discrimination of double stimulation (Frahm et al., 2018; Mørch et al., 2010).…”

Local hyperexcitability of C-nociceptors may predict responsiveness to topical lidocaine in neuropathic pain

“…Cutaneous electrical stimulation is generally used to activate peripheral axons. The geometry of the electrodes and the temporal stimulation profile is critical for a selective activation of peripheral nerve fibers [ 10 – 14 ]. Slowly depolarizing transcutaneous currents of low-intensity with 4 Hz sinusoidal stimulation profile as well as single 500 ms half sine wave pulses can be used to stimulate nociceptors in human skin [ 15 – 18 ].…”