How mysterious is the placebo effect?

▎The editor of WuXi AppTec’s content team said that one of the coolest and strangest things in the medical field is the placebo effect: drugs or “fake” interventions that do not contain active ingredients are just patients.
Believe it is effective", you can improve your health.

A typical example is the placebo effect of analgesics.
There are many clinical trials showing that "fake" analgesics or analgesic surgery can really relieve the pain of patients, even the effect is no different from the real surgery.

Image source: 123RF Pain is an experience produced by the brain through complex neural activities.

So, what happens in the brain when using a placebo that makes us "deceive ourselves" like this? Recently, a meta-analysis study published in Nature Communications, a sub-issue of "Nature", answered this question.

Scientists pointed out that in order to find the neural mechanism behind the placebo effect, there have been some small-scale studies in the past, but this time through the first large-scale meta-analysis, focusing on the analysis of the whole brain images of a single participant, the participation can be analyzed in detail The various brain regions where pain is established, so as to have a deeper understanding of the placebo effect.

The researchers synthesized 20 neuroimaging studies for this purpose and looked at the brain activity of more than 600 healthy participants in detail.

All participants stated that they had “treated” to reduce their pain, but the researchers wanted to find out whether the brain responded to the placebo in a meaningful way.

For example, does a placebo change the way the brain generates pain, or does it change people's thinking about pain after the fact? Image source: 123RF After a large-scale sample analysis, the researchers located the placebo effect to specific brain areas, such as thalamus.

The thalamus can be regarded as a portal for various sensory inputs such as vision and sound.
It is composed of many nuclei, like different workstations, used to process different types of sensory inputs.

The results showed that the nucleus, which is most important for pain management, was most strongly affected by the placebo.

Another brain area essential for early processing of pain information, the somatosensory cortex, is also affected by the placebo effect.

In addition, the placebo effect affects the basal ganglia, which is a very important brain area that links pain with other experiences and behaviors.

"Placebo can reduce your pain experience, including feelings of pain and motivating you to take actions to avoid pain,
" explained Professor Tor Wager, who led the study.

The study also found that placebo treatment reduced activity at the back of the insula, which means that the pathways of pain formation are affected.

▲Functional MRI showed that during the pain process, the activity of the brain area (blue) related to the construction of pain experience decreased, and the activity of the brain area related to cognition and memory (red and yellow) increased (picture source: reference [2] ) Another area of ​​interest is the prefrontal cortex, which is an important brain area related to higher cognitive functions.

When we expect pain, this area will be activated, which helps us to keep track of the background of the occurrence of pain and confirm the existence of pain.

However, the researchers found that in different studies, the activity of the prefrontal cortex was not consistent, and no specific area was continuously activated.

This suggests that the way the placebo is administered, people's thinking, the way of thinking and other factors may affect the placebo effect.

"In general, this shows that the placebo effect is not limited to sensory (noxious feelings) or cognitive (emotional) processes, but is more like a synthesis of multiple mechanisms, so it will produce results that vary from person to person.

" The professor said, "We hope that these results can contribute to the development of brain biomarkers that can be used to predict the response of different people to placebo, which helps to distinguish the placebo effect from the pain relief response of the drug.

"Scientists believe that understanding the neural mechanism of the placebo effect is of great significance for clinical and drug development.
When we combine specific situations and target specific diseases, we can use the placebo effect in a more effective way, and ultimately we can bring better results for patients.
Therapeutic effect.

Reference materials [1] Matthias Zunhammer et al.
, (2021) Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data.
Nature Communications.
Doi: https://doi.
org/10.
1038/s41467- 021-21179-3[2] Study Provides Deep Dive on the Neuroscience of Placebo Effects.
Retrieved March 3, 2021 from https://news.
dartmouth.
edu/news/2021/03/study-provides-deep-dive-neuroscience -Placebo-effects Academic Jingwei Reader Interest Survey Questionnaire "Academic Jingwei" is an academic public account created by WuXi AppTec's content team, dedicated to delivering important academic news in the field of biomedicine as soon as possible.

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