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.