Expectation to feel more pain disrupts the habituation of laser-pain rating and laser-evoked potential amplitudes

Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: (1) the mere expectation to feel more pain after the administration of an inert drug can affect the laser-pain rating and the laser-evoked potential (LEP) amplitude, and (2) the learning potentiates the nocebo effect. Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laser pain and LEP amplitude to right hand stimulation. They were randomly assigned to either "verbal session" or "conditioning session". In the "verbal session", LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the "conditioning session", after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased the pain sensation. Then, the cream was reapplied, and LEPs were recorded at the same stimulus intensity as at the baseline. It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Unlike previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect.