Measuring expectation of pain: Contingent negative variation in placebo and nocebo effects

Background: Expectation is an important mechanism underlying placebo response. Here, we analysed expectation of placebo hypoalgesia and nocebo hyperalgesia by using, for the first time, the contingent negative variation (CNV), also known as expectancy wave. Methods: Subjects were presented a green or red cue followed by a train of either non painful or painful electrical stimuli, and expected hypoalgesia after the green and hyperalgesia after the red cue. In experiment 1, expectation was reinforced using a conditioning procedure whereby the green and red cues were paired with non painful and painful stimuli, respectively (acquisition). In a second session (test) the intensity of the stimuli was kept constant, regardless of cue. In experiment 2 no conditioning was performed and participants expected an altered pain perception indicated by the visual cues. CNV mean amplitude, time necessary to stop the train of stimuli (reaction time) and pain ratings were measured. Results: A difference in pain perception occurred when electrical stimuli followed the presentation of the green cue compared to the red in the test session, whereas reaction times showed no changes. The same difference occurred in the early CNV component, related to cognitive stimulus anticipation, whereas the late CNV component, related to motor preparation, did not change. Moreover, these differences in pain perception and CNV amplitude were less robust in the experiment 2. Conclusion: Placebo hypoalgesia and nocebo hyperalgesia differently affect sensory (pain perception) and motor components (pain avoidance) of pain. Furthermore, CNV is an electrophysiological objective measure capable of dissecting these components. Significance: Dissection of placebo hypoalgesia, differentiating the sensory component (pain perception) from the motor component (pain avoidance). Study of these components using the contingent negative variation (CNV) as an electrophysiological objective measure.