Nocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect... Show moreNocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect description on a medication leaflet. Nocebo hyperalgesia, i.e., increased pain sensitivity due to nocebo effects, can be acquired via learning in both healthy and clinical populations, and has a large social and economic impact on healthcare. In the current dissertation, we investigated the experimental learning mechanisms behind the acquisition and recovery of nocebo hyperalgesia in healthy individuals and in patients with fibromyalgia, and the potential differences between groups. Additionally, we investigated the predictors of nocebo hyperalgesia acquisition and recovery to identify individuals who are more susceptible to these effects. Lastly, we stepped outside of the lab-settings and in an electronic diary study, examined the role of (experimentally-induced) nocebo hyperalgesia in daily pain progression of patients with fibromyalgia. The current dissertation offers insights for better understanding the expectancy and learning mechanisms behind nocebo hyperalgesia in individuals with and without chronic pain. These can be useful for the future design of personalised learning-based interventions for targeting nocebo effects on pain. Show less
Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy... Show moreNocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of nocebo effects on pressure pain at baseline (N = 69) and 1-month follow-up (N = 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions on the pain-increasing function of a sham transcutaneous electrical nerve stimulation device, then decreased via extinction. One month later, the same procedures were repeated to explore their stability. Results suggest that nocebo effects were induced in the healthy control group during baseline and follow-up. In the patient group, nocebo effects were only induced during follow-up, without clear group differences. Extinction was only observed during baseline in the healthy control group. Further comparisons of nocebo effects and extinction indicated no significant changes across sessions, possibly suggesting their overall magnitudes were stable over time and across groups. In conclusion, contrary to our expectations, patients with fibromyalgia did not have stronger nocebo hyperalgesia; instead, they might be less responsive to nocebo manipulations than healthy controls. Show less
Objectives:The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia... Show moreObjectives:The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia and psychological characteristics. Methods:Nocebo effects on pressure pain were first experimentally induced in 83 healthy female participants through conditioning with open-label instructions about the pain-worsening function of a sham TENS device to assess susceptibility to nocebo hyperalgesia. Participants were then randomized to 1 out of 2 nocebo-reduction conditions (counterconditioning/extinction) or to continued nocebo-conditioning (control), each combined with open-label instructions about the new sham device function. Dispositional optimism, trait and state anxiety, pain catastrophizing, fear of pain, and body vigilance were assessed at baseline. Results:The results showed that lower optimism and higher trait anxiety were related to a stronger induction of nocebo hyperalgesia. Moreover, a stronger induction of nocebo hyperalgesia and higher trait anxiety predicted a larger nocebo reduction across interventions. Also, nocebo hyperalgesia and optimism moderated the effects of the nocebo-reduction interventions, whereby larger nocebo hyperalgesia and lower optimism were associated with a larger nocebo reduction after counterconditioning, compared with control, and also extinction for larger nocebo hyperalgesia. Discussion:Our findings suggest that open-label conditioning leads to stronger nocebo hyperalgesia when trait anxiety is high and dispositional optimism is low, while these psychological characteristics, along with larger nocebo hyperalgesia, also predict open-label counterconditioning to be an effective nocebo-reduction strategy. Susceptibility to nocebo hyperalgesia, trait anxiety, and dispositional optimism might be indicators of a flexible pain regulatory system. Show less
The aim of the current dissertation was to explore the link between the endocrine system and placebo effects with a focus on the hormone oxytocin. Two perspectives were examined: the possibility to... Show moreThe aim of the current dissertation was to explore the link between the endocrine system and placebo effects with a focus on the hormone oxytocin. Two perspectives were examined: the possibility to elicit placebo effects in the endocrine system and influencing placebo and nocebo effects by hormones. In the first part of the dissertation possibility to induce placebo effects in the endocrine system with classical conditioning is explored. A systematic review of literature and the results of a large randomized controlled trial on classical conditioning of oxytocin are described in this part. In the second part of the dissertation we explored the possibility to influence placebo and nocebo effects with oxytocin. In this part results of two randomized controlled trials are presented. We demonstrated that there is accumulating evidence in the literature that placebo effects can be elicited in the endocrine system. Moreover, we described results of a randomized controlled trial in which we successfully conditioned oxytocin release. Finally, we showed a lack of evidence that oxytocin can influence placebo and nocebo effects. Show less
Itch is a commonly experienced symptom of acute and chronic dermatological and systemic conditions. Placebo and nocebo effects, positive and negative effects experienced after both real and sham... Show moreItch is a commonly experienced symptom of acute and chronic dermatological and systemic conditions. Placebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can have a significant impact on the experience of itch and its treatment. Experimental methods to induce and study placebo and nocebo effects on itch have been developed, utilizing various combinations of expectancy-induction methods (eg, conditioning, verbal suggestions) and short-acting itch-evoking stimuli (eg, histamine, electrical, or mechanical stimulation). The aim of this review is to describe the current research methods used to induce placebo and nocebo effects on itch, and the results of these studies. The benefits and drawbacks of different expectancy-induction methods and itch-evoking stimuli are described, and future directions for research and clinical application are discussed. Show less
