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.

Offset analgesia: The role of peripheral and central mechanisms.

BACKGROUND: Offset Analgesia (OA) can be evoked by a three-heat-stimulus train (T1-T2-T3), with T1 (5 s) and T3 (20 s) having the same temperature (e.g. 48 °C) and T2 (5 s) being slightly higher (1-3 °C). OA is defined as a disproportional pain reduction caused by the slight temperature decrease from T2 to T3. As the pain modulatory mechanisms behind OA are still poorly understood, the current study aimed to investigate the role of peripheral and central mechanisms by applying heat stimuli to the same location and to different unilateral and bilateral locations. METHOD: Young healthy volunteers participated in the study. A 'standard-OA' paradigm (48-49-48 °C) was applied to the non-dominant volar forearm (T1-T2-T3 applied on the same location). 'Unilateral-OA' trials were applied on three different locations of the non-dominant volar forearm (the same dermatome). 'Bilateral-OA' trials were applied by shifting T1-T2-T3 between dominant and non-dominant volar forearms. A constant stimulus of 48 °C was applied as control for the evoked pain. The pain intensities were continuously recorded using an electronic visual analogue scale. RESULTS: The largest pain intensity reduction was reported for the 'standard-OA' paradigm (p < 0.001) compared with the control stimulus. Both 'Unilateral-OA' and 'Bilateral-OA' trials caused a significant pain reduction (p < 0.05) compared with the control; however, the pain reduction was less than that evoked by 'standard-OA' (p < 0.05). CONCLUSION: This study showed that OA could be elicited when the stimuli were applied both to the same and to different locations (ipsi- and contralateral) indicating that peripheral as well as central mechanisms are involved in mediating OA. SIGNIFICANCE: This study investigated offset analgesia by applying thermal painful stimuli to the ipsi- and bilateral forearms in healthy subjects and found that both peripheral and central mechanisms seem to mediate offset analgesia.