Standardized Stimulation Protocols Are Needed for Comparable Analysis of Pain-related Evoked Potentials (PREP)

Objective: Pain-related evoked potentials (PREP) are increasingly used to investigate nociception and small-fibre function . Due to lack of a standard stimulation protocol, it is unclear whether results from studies using different protocols are comparable. Aim of the study was to assess the influence of different stimulation parameters on N1P1-amplitudes, N1-latencies and PREP-induced pain intensity. Methods: : In a cross-over design we examined 31 healthy volunteers using four different stimulation protocols (number of stimulation electrodes 1 vs. 3, stimulus durations 200 µs vs. 500 µs) in a randomized order. Statistics: paired t-test, ANOVA, correlation analyses. Results: : Longer stimulus duration induced higher N1P1-amplitudes (p<0.05) and higher pain intensity (p<0.001). Stimulation with 3 electrodes lead to a lower pain intensity (p<0.01), whereas the N1P1-amplitude and stimulus intensity at twofold of individual pain remained unaffected by the number of electrodes. Also, there was no relation between stimulus intensities and N1P1-amplitudes (one electrode: r=0.079; p=0.646, three electrodes: r=-0.10, p=0.70) was observed. N1-latencies remained comparable between the four protocols. Conclusions: and Significance: The use of different stimulation protocols for PREP is limited by relevant differences in the N1P1-amplitudes and evoked pain intensities. Standard consented stimulation protocols are needed to allow data comparison between different labs and studies.