Nocebo hyperalgesia and the startle response

- Nocebo suggestions combined with placebo treatment increased startle.
- Startle responses were predictive for nocebo hyperalgesic responses.
- Nocebo suggestions increased startle responses that facilitated pain increase.
- Nocebo suggestions activated cortical defensive processes measured by startle.

Background: The literature on the effects of nocebo on pain is sparse. The present experimental study investigated whether suggestions of nocebo hyperalgesia modified the startle response and whether increased startle contributed to the nocebo hyperalgesic effect. Methods: A design with four groups was employed; the participants were randomized into either a placebo group, a natural history group, or into two nocebo groups. The participants in the placebo and nocebo groups received suggestions of pain decrease or pain increase, together with a placebo or nocebo cream applied to the lower arm, respectively. Heat pain was induced by a PC-controlled thermode before and after the treatment. White noise was used to elicit startle responses. Startle was assessed by measuring eye blink electromyographic responses recorded from the right orbicularis oculi muscle. Results: The results showed that nocebo suggestions increased reports of pain and startle responses. Increased startle was significantly associated with the nocebo hyperalgesic response. Conclusions: The results of the present study suggest that verbally induced expectations of increased pain engage cortical physiological defensive systems that in turn mediate the experience of increased pain.