| Peer-reviewed | Experimental study | Humans |
Negative expectations can worsen perceived pain more strongly – and for longer – than positive expectations can make it feel better, according to new research.
The study, published recently as a Reviewed Preprint in eLife, is described by the editors as valuable, with the potential for a significant impact in the field of experimental and clinical pain. They say the authors’ rigorous methodology to compare the magnitude and duration of placebo and nocebo effects in pain perception yields compelling evidence that nocebo responses demonstrate consistently greater strength.
Placebo and nocebo effects refer to the power of expectation in shaping how we experience symptoms. A placebo effect occurs when a person feels better simply because they believe a treatment will help, even if it is inactive. On the other hand, a nocebo effect is when someone feels worse because they expect a negative outcome, even without a physical cause.
“While many studies have explored placebo and nocebo effects individually, few have directly compared the two in the same people over time,” says co-lead author Katharina Schmidt, a senior postdoc at the Department of Neurology, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Duisburg-Essen, Germany. “We set out to determine whether negative expectations towards treatment have a stronger or longer-lasting effect on pain perception than positive ones. This is important because in clinical settings, both types of expectations can be triggered by how doctors and nurses communicate – and potentially shape patient outcomes.” Schmidt served as lead author of the study alongside Angelika Kunkel, also a postdoc at C-TNBS, University Duisburg-Essen.
To assess and compare placebo and nocebo effects, the team studied 104 healthy volunteers across two sessions one week apart. On the first day, participants were exposed to short bursts of heat pain after being led to expect either pain relief (placebo), increased pain (nocebo), or no change (control). These expectations were created using a combination of verbal suggestions and a fake pain relief treatment – a sham nerve stimulation device that appeared real but delivered no actual relief. Participants were asked to rate the intensity of their pain on a scale between 0 (not painful at all) and 100 (unbearably painful).
Unbeknownst to participants, the researchers subtly adjusted the heat stimulus to reinforce their expectations – making it less painful in the placebo condition and more painful in the nocebo condition. In the second session, the pain stimulus was kept identical across all conditions, allowing the team to test whether expectations formed on the first day continued to shape participants’ pain perception.
Their results showed that both placebo and nocebo suggestions significantly influenced pain perception – but the nocebo effect was stronger. On the first day, participants in the nocebo condition rated their pain on average 11.3 points higher than the control condition. Whereas in the placebo condition, participants rated their pain only 4.2 lower than the control. When participants returned one week later for the second session, these patterns persisted. The nocebo effect remained stronger than the placebo effect: participants in the nocebo condition reported pain ratings 8.9 points higher than the control, whereas the placebo effect was again more modest, with pain ratings just 4.6 points lower than the control.
“This suggests that people are more likely to expect and feel worse outcomes than better ones,” says Schmidt. “It reflects a ‘better-safe-than-sorry’ strategy – humans may have evolved to be more attuned to potential threats, making negative expectations carry more weight.”
The team also found that recent experience of pain had a greater impact on participants’ future responses than verbal suggestions alone. For example, those who experienced a strong placebo or nocebo effect on the first day were more likely to show the same response a week later. Psychological traits played a role too: people who tend to feel normal body sensations as stronger and more uncomfortable showed weaker placebo effects, while those who rated the experimenter as highly competent were more susceptible to nocebo effects – possibly because they found the negative suggestions more believable.
The authors note that the study was conducted using experimental pain in healthy volunteers. Further research is needed to determine how these effects apply in clinical settings.
“Our findings highlight the enduring nature of both placebo and nocebo effects in pain, with nocebo responses showing consistently greater strength over time,” says senior author Ulrike Bingel, Director of the Interdisciplinary Center for Pain Medicine and Translational Pain Research at the Department of Neurology, C-TNBS, University Duisburg-Essen. “While we often focus on boosting positive expectations in patients, we show that it may be just as important – if not more so – to avoid unintentionally creating negative ones, which appear to be more easily triggered.”
“Nocebo effects can be prevented using simple, effective strategies to improve communication between patients and practitioners,” adds Bingel. “Positive framing, avoiding unnecessary emphasis on side effects, and building a trusting relationship can all reduce the risk of triggering nocebo responses. In a time when cost-effectiveness in healthcare is essential, preventing nocebo effects should be a key strategy for improving treatment outcomes.”
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This work was conducted as part of the Collaborative Research Center “Treatment Expectation,” funded by the German Research Foundation (DFG). TO learn more about our research, please visit: https://treatment-expectation.de/
Media contacts
Emily Packer
eLife
e.packer@elifesciences.org
+441223855373George Litchfield
eLife
g.litchfield@elifesciences.orgUlrike Bingel
C-TNBS, University Duisburg-Essen
ulrike.bingel@uk-essen.de
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