The heart is a powerful medicine. For an ineffective treatment, patients can experience real health improvements simply by believing that the treatment is working – the placebo effect. But this sweet trick has a dark side: when a harmless place is effective, it becomes harmful, too, causing the side effects seen in actual cures.
In a new study exploring this mysterious “nocebo effect,” researchers pointed to areas of the brain that appear to be behind the powerful traumas. They also examine factors—frame and cost—that can increase the power of the effect. These could be important to the design and evaluation of clinical practices and test results, they argue.
Specifically, researchers gave patients a sham anti-itch cream for eczema (atopic dermatitis) and told them that it increased sensitivity to pain as a side effect—which is a side effect of real drugs, but the phony cream didn’t. and have any side effects. . However, patients did not report more pain, but the amount of pain they reported depended on the price of the cream and the packaging. The cream caused more pain in patients when they were told it had a heavy price tag and was in a brand-name container, compared with when they thought it was a cheap cream that comes in a generic looking box. The researchers, led by neuroscientist Alexandra Tinnermann of the University Medical Center Hamburg-Eppendorf, published the results recently Knowledge.
Patients reported no increased pain when using the control cream, even though the same numbing cream was used for all three types: expensive, cheap, and control. The only differences are the prices, the packaging, and the expectations of the patients. Researchers note that patients expect an expensive, brand-name drug to be more convenient than a cheap knock-off. So it will be more powerful and have stronger side effects.
Inside Next editorPain and placebo expert Luana Colloca said the findings show that nocebo effects can skew clinical research data and patient adherence to medications.
For these effects, Dr. Colloca recommends:
We should consider how to avoid them in clinical trials and practices – for example, by improving patient-patient communication to balance true information about adverse events with expectations of improved outcomes, explore treatment beliefs patients and negative medical history, and pay attention to grafting (i.etreatment description) and contextual effects (i.evaluation).
The worst placebo
For the study, Tinnermann and colleagues recruited 49 healthy participants and told them that the experiment was comparing the painful side effects of two creams, one cheap and one expensive. Twenty-five participants had the expensive cream and the remaining 24 tested the less expensive one. As indicated, the researchers also included a “control cream” that would allegedly have no side effects. In fact, all studies used only this type of cream, which has no active ingredient.
Next, the researchers primed the participants for the “nocebo effect” so they could test how the cream’s price and packaging changed said effect. To do this, the researchers used a delusional pain test. Each participant puts some “control cream” on one patch of their left arm and some “test cream” (expensive or cheap) on a different patch of the same forearm. After 30 minutes of burn-in time, the researchers removed the creams and used a small device that would deliver the pain relief of heat. The researchers told the participants that the device would send the same painful flash to each patch of treated skin.
On the skin treated with the control cream, the machine delivers a small blast of heat that will register as “30” on the pain sensitivity scale adjusted for each participant. But, on a test skin patch, the device delivered a more painful blast to register as “70.”
This little lie feeds into the participant’s expectations that the test creams (cheap or expensive) will increase pain sensitivity, while the control cream will not.
Next, the researchers repeated the pain test 16 times with each participant over several days. But, for these tests, the researchers put the pain points that all should have registered as “50” on the calibrated pain scales, regardless of the cream treatment. While all this is going on, the participants are in an MRI machine so the researchers can monitor their brain and spinal cord activity.
As expected, the participants showed a nocebo effect, averaging pain levels higher than 50 on the skin treated with the test creams, but around 50 for the skin treated with the control cream.
Also, participants who tested the supposedly expensive cream reported more pain than those who thought they tested the cheap cream. And the expensive cream seemed to become more painful on 16 tests. In the early stages, the dead cream testers registered around 55 on the pain scale, while the expensive cream testers reached around 60. In the end 16 tests, the minimum pain levels stayed about the same, but the expensive examiners’ pain jumped to 70 on the scale.
When the researchers looked at the MRI data, they found that there was more activity in the spinal cord regions of the cash-strapped testers. This suggests that testers are not imagining and reporting more pain—they are actually feeling it.
The researchers also identified areas of the brain that seem to be involved in the overall nocebo effect. These are the rostral anterior cingulate cortex and the periaqueductal gray, which are involved in high-level activity and pain, respectively.
Taken together, the data suggest that the cost of the cream not only changes pain reporting but also activity in the body’s pain syndrome. It “modifies the connection between the frontal regions, the brain, and the spinal cord,” Tinnermann and his colleagues concluded. And this could give researchers advice on how to tap into and alter early pain processing.
Knowledge2017. DOI: 10.1126 / science.aan1221 (About DOIs).