Electrical stimulation for evoking offset analgesia: A human volunteer methodological study

Background: Offset analgesia (OA) is a disproportionally large decrease in the pain perception in response to a small decrease in the stimulation intensity. Traditionally, heat stimulation has been used to evoke OA. The aim of this study was to investigate whether OA could be evoked by electrical stimulation. Methods: Healthy volunteers (N = 24) underwent two OA-experimental sessions consisting of heat stimuli intensities of 48-49-48 °C (traditional OA-paradigm) and electrical stimuli at 150%-180%-150% of the electrical pain perception (EPP) threshold. The three stimuli were delivered for 5 s (STIM1), 5 s (STIM2) and 20 s (STIM3), respectively. The sessions were randomized to the dominant or nondominant volar forearm. Two control sessions were performed with 30 s constantly heat (48 °C) and electrical stimuli (150% of the EPP) (CONTROL-STIM). In all sessions, the pain intensities were constantly rated on a Visual Analog Scale (VAS, 0-10). Results: Significantly reduced STIM3 VAS ratings as compared to the CONTROL-STIM were reported for heat (1.81 ± 0.54; p < 0.001) and electrical (2.12 ± 0.42; p < 0.001) stimuli. The degrees of OA produced by heat and electrical stimuli were similar. A significantly positive correlation was found between thermal and electrical OA-effects (r = 0.48, p < 0.02). Conclusions: These findings demonstrate that electrical stimulation can elicit significant OA in humans indicating that the peripheral receptors can be bypassed and still evoke OA. Application of the electrical OA model may be of interest for further basic and clinical investigations as a potential new biomarker for central pain inhibition and provide the option to back-translate the technology to animals to understand the underlying neurobiology. Significance: Electrical stimulation can elicit offset analgesia in humans, indicating that this perceptual modification can be obtained even bypassing peripheral receptors.