Temporal properties of pain contrast enhancement using repetitive stimulation

Background: Offset analgesia (OA) is characterized by a disproportionately large reduction in pain following a small decrease in noxious stimulation and is based on temporal pain contrast enhancement (TPCE). The underlying mechanisms of this phenomenon are still poorly understood. This study is aiming to investigate whether TPCE can also be induced by repetitive stimulation, i.e., by stimuli clearly separated in time. Methods: A repetitive TPCE paradigm was induced in healthy, pain-free subjects (n = 33) using heat stimuli. Three different interstimulus intervals (ISIs) were used: 5, 15, and 25 s. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated perceived pain intensity. In addition, electrodermal activity (EDA) was recorded as a surrogate measure of autonomic arousal. Results: Temporal pain contrast enhancement was confirmed for ISI 5 s (p < 0.001) and ISI 15 s (p = 0.005) but not for ISI 25 s (p = 0.07), however, the magnitude of TPCE did not differ between ISIs (p = 0.11). A TPCE-like effect was also detected with increased EDA values. Conclusions: TPCE can be induced by repetitive stimulation. This finding may be explained by a combination of the mechanisms underlying the OA and a facilitated pain habituation. Significance: This experiment shows for the first time that temporal contrast enhancement of pain can be elicited by stimuli that are clearly separated in time with an interstimulus interval below 25 s.