Quantification of the variability of detection thresholds to intra-epidermal electrical stimulation in humans

F. G. ARGUISSAIN; J. A. BIURRUN MANRESA; O. K. ANDERSEN; VAN DE BROEKE, EMANUEL

Boston

Congreso; 17th World Congress on Pain; 2018

International Association for the Study of Pain (IASP)

Aim of the investigation: Intra-epidermal electrical stimulation (IES) is an alternative to laser stimulation for the preferential activation of cutaneous nociceptors [1]. IES is a relatively new methodology that involves the use of specially-designed electrodes to deliver electrical stimuli at very low intensities, normally in the vicinity of the detection threshold (DTh). As such, several methodological factors that potentially affect the variability of DTh remain unexplored: two examples are whether there exist differences in DTh depending on which arm it is applied, or on how many pulses are delivered for the assessment of DTh [2]. Thus, the aim of this study was to determine the variability of DTh to IES, by comparing differences in DTh between stimuli consisting of either one or two pulses applied to both arms of the same subject.Methods: eighteen healthy volunteers (7 women and 11 men, age 27,1 ± 3,43 years [mean ± sd]) participated in one single experimental session. Participants seated in a comfortable chair with their arms resting in supine position. IES was administered in the volar surface of both arms, and stimuli consisted of either one or two constant-current square-wave pulses. The pulses had a duration of 0.5 ms and were separated by 10 ms in the 2-pulse condition. IES was delivered by means of a stainless steel concentric bipolar needle electrode [1]. The DThs were determined using an automatic staircase procedure. The subjects indicated the detection of the stimulus by pushing a button as soon as they perceived it. The stimuli were delivered every 5-8 s. The order of the stimulation site (dominant or non-dominant side) and stimulation type (one or two pulses) was randomized across subjects. Differences in mean DTh between arms for one- and two-pulse IES were analyzed using a two-way repeated measures analysis of variance (RM ANOVA), with factors arm (dominant vs. non-dominant) and stimulus type (one- vs. two-pulse IES). Additionally, the variability in DTh was assessed using Bland?Altman analysis, in which bias (defined as the mean difference in DTh between arms) and 95% limits of agreement (LoA, defined as the range within which 95% of the differences in DTh between arms are expected to lie) were reported. The 95% confidence intervals for these indexes were also calculated and reported.Results: RM ANOVA revealed a statistically significant difference in DTh due to stimulus type (one-pulse IES: 142 ± 53 µA; two-pulse IES: 77 ± 27 µA; F (1,17) = 37.24, p < 0.001). No difference was found between arms (dominant: 114 ± 44 µA; non-dominant: 104 ± 44 µA; F (1,17) = 0.709, p = 0.411) and no significant interaction was found either (F (1,17) = 2.444, p = 0.136). With regards to Bland-Altman analysis, the DTh for one-pulse IES presented a mean difference of 23 µA between arms (95% CI: -19 to 66 µA), whereas the mean difference between arms was -2 µA (95% CI: -22 to 18 µA) for the two-pulse IES. Furthermore, the upper LoA were 190 µA (95% CI: 116 to 263 µA) for the one-pulse IES and 74 µA (95% CI: 39 to 109 µA) for the two-pulse IES, whereas the lower LoA were -143 µA (95% CI: -217 to -70 µA) for the one-pulse IES and -78 µA (95% CI: -113 to -43 µA) for the two-pulse IES. Conclusions: two-pulse IES resulted in lower and less variable (i.e. more reliable) thresholds. This is relevant since lower DThs entail less chances of activating large myelinated fibers. Furthermore, mean differences in DTh between arms were negligible for two-pulse IES (~ 2 µA), which means that, for a given group of subjects, DTh will not be higher or lower in the dominant arm compared to the non-dominant arm. However, the LoA are quite wide (~ 75 µA), which indicates that the intra-individual difference in DTh between arms can be substantial. This is particularly relevant in experimental setups using one arm for treatment and the other arm as control, in which these intra-individual differences should be accounted for.