Negative expectations may have a longer impact on pain perception than positive expectations or placebo effects, according to new research.
In a recent study, investigators found that the “nocebo effect,” when an individual has negative expectations, resulted in more intense pain when the patient expected worse outcomes compared with the placebo effect, which resulted in weaker outcomes for pain relief.
The findings suggest that the brain may be wired to prioritize perceived
MAY 23, 2025
Negative Expectations May Have Stronger, Longer-Lasting Impact on Pain Than Positive Ones
Negative expectations may have a longer impact on pain perception than positive expectations or placebo effects, according to new research.
In a recent study, investigators found that the “nocebo effect,” when an individual has negative expectations, resulted in more intense pain when the patient expected worse outcomes compared with the placebo effect, which resulted in weaker outcomes for pain relief.
The findings suggest that the brain may be wired to prioritize perceived threats, with the nocebo effect persisting even a week after the initial experience. This could have implications for how clinicians communicate with patients, potentially shaping treatment outcomes based on expectations.
In the study, the investigators assessed and compared both placebo and nocebo effects in 104 healthy volunteers across two sessions that were one week apart. Each participant was exposed to short bursts of heat pain on the first day after being led to expect pain relief, increased pain or no change.
T
he investigators created the expectations using both verbal suggestions and a fake pain relief treatment using a sham nerve stimulation device that provided no actual relief. Each participant was asked to rate the pain intensity on a 0-to-100 scale.
Without the patients’ knowledge, the researchers adjusted the heat stimulus to reinforce the expectations of less pain in the placebo group or more pain in the nocebo group.
In the second session, the pain stimulus was identical across all groups.
The results showed that placebo and nocebo suggestions influenced pain perception. However, nocebo effects were stronger than the placebo. On day 1, the pain score was 11.3 points higher on average in the nocebo group compared with the control group, while the placebo group rated their pain 4.2 points lower than the control group. At the one-week mark, the nocebo group rated pain 8.9 points higher than control, while the placebo group rated pain 4.6 points lower than control.
The results also showed that recent pain experiences had a bigger impact on future responses than just verbal suggestions.
“While many studies have explored placebo and nocebo effects individually, few have directly compared the two in the same people over time,” said co-lead author Katharina Schmidt, a senior post-doctoral scientist in the Department of Neurology, Center for Translational Neuro- and Behavioral Sciences , University Duisburg-Essen, in Germany.
“We set out to determine whether negative expectations toward 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 [can] shape patient outcomes.”
—Kenny Walter
In a recent study, investigators found that the “nocebo effect,” when an individual has negative expectations, resulted in more intense pain when the patient expected worse outcomes compared with the placebo effect, which resulted in weaker outcomes for pain relief.
The findings suggest that the brain may be wired to prioritize perceived threats, with the nocebo effect persisting even a week after the initial experience. This could have implications for how clinicians communicate with patients, potentially shaping treatment outcomes based on expectations.
In the study, the investigators assessed and compared both placebo and nocebo effects in 104 healthy volunteers across two sessions that were one week apart. Each participant was exposed to short bursts of heat pain on the first day after being led to expect pain relief, increased pain or no change.
T
Without the patients’ knowledge, the researchers adjusted the heat stimulus to reinforce the expectations of less pain in the placebo group or more pain in the nocebo group.
In the second session, the pain stimulus was identical across all groups.
The results showed that placebo and nocebo suggestions influenced pain perception. However, nocebo effects were stronger than the placebo. On day 1, the pain score was 11.3 points higher on average in the nocebo group compared with the control group, while the placebo group rated their pain 4.2 points lower than the control group. At the one-week mark, the nocebo group rated pain 8.9 points higher than control, while the placebo group rated pain 4.6 points lower than control.
The results also showed that recent pain experiences had a bigger impact on future responses than just verbal suggestions.
“While many studies have explored placebo and nocebo effects individually, few have directly compared the two in the same people over time,” said co-lead author Katharina Schmidt, a senior post-doctoral scientist in the Department of Neurology, Center for Translational Neuro- and Behavioral Sciences , University Duisburg-Essen, in Germany.
“We set out to determine whether negative expectations toward 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 [can] shape patient outcomes.”
—Kenny Walter