The brain mechanisms behind the placebo: why do you feel less pain?

A large part of the benefit that a person gets from taking a real drug or receiving pain relief treatment is due to the individual’s mindset, not the medication itself. Understand the neural mechanisms that drive this Placebo effect It has been a long-standing issue. A meta-analysis published in Nature Communications finds that placebo treatments to reduce ailment, known as placebo analgesia, reduce pain-related activity in multiple areas of the brain.

Previous studies of this type have been based on small-scale research, thus, until now, the scientists did not know whether the neural mechanisms underlying the placebo effects observed to date would hold up in larger samples. This study, which represents the first large-scale meta-analysis analyzing the whole brain images of individual participants, It allowed the researchers to look at parts of the brain that didn’t have enough resolution to look at in the past.

The analysis consisted of 20 neuroimaging studies with 600 healthy participants. The results provide a new perspective on the size, location, importance and heterogeneity of placebo effects on pain-related brain activity.

The research reflects the work of an international collaborative effort of the Placebo Neuroimaging Consortium, led by Tor Wager from the department of neurology at Essen University Hospital. The meta-analysis is the second with this sample and builds on the team’s previous research using a pain marker established by Wager’s lab.

“Our findings show that participants who showed the greatest reduction in pain with placebo also revealed the greatest decreases in areas of the brain associated with the construction of pain”Explains co-author Wager, who is also the principal investigator at the Laboratory for Cognitive and Affective Neuroscience at Dartmouth.

“We are still learning how the brain constructs pain experiences, But we know that it is a mixture of areas of the brain that process information from the body and those involved in motivation and decision-making. Placebo treatment reduced activity in areas involved in early pain signaling from the body, as well as motivational circuits not specifically related to pain ”.

On In all studies in the meta-analysis, participants had indicated that they felt less pain; however, the team sought to find out whether the brain responded to the placebo in a meaningful way.

Is it real or is it mental placebo

¿The placebo is changing the way a person constructs the experience of pain or is changing the way a person thinks about it after the fact? Does the person really feel less pain? Those were two basic questions that the researchers tried to elucidate in their research.

The thalamus serves as a gateway for images and sounds and all kinds of sensory motor information. It has many different cores, which act as processing stations for different types of sensory information. The results showed that the parts of the thalamus that are most important for pain sensation were most affected by the placebo.

What’s more, parts of the somatosensory cortex were also affected, which are an integral part of the early processing of painful experiences.

The placebo effect also affected the basal ganglia, which are important for motivation and for connecting pain and other experiences with action.. “The placebo can affect what you do with the pain and how it motivates you, which could be a bigger part of what’s going on here,” says Wager. It is changing the circuit that is important for motivation ”.

The findings revealed that placebo treatments reduce activity in the posterior insula, which is one of the areas that are involved in the early construction of the pain experience. This is the only site in the cortex that can stimulate and invoke the sensation of pain. The main ascending pathway of pain is from parts of the thalamus to the posterior insula. The results provide evidence that the placebo affects that pathway of how pain is built.

Previous research has shown that with placebo effects, the prefrontal cortex is activated in anticipation of pain. The prefrontal cortex helps to keep track of the context of pain and to maintain the belief that it exists. When the prefrontal cortex is activated, there are pathways that trigger the release of opioids in the midbrain that can block pain and pathways that can modify the signaling and construction of pain.

The team found that activation of the prefrontal cortex is heterogeneous between studies, meaning that particular areas in this region were not activated consistently or strongly in the studies. These differences between studies are similar to those found in other areas of self-regulation, where different types of thoughts and mindsets can have different effects.

For example, other work in Wager’s lab has found that rethinking pain through the use of images and storytelling normally activates the prefrontal cortex, but conscious acceptance does not. The effects of the placebo likely involve a combination of these types of processes, depending on the details of how it is administered and people’s predispositions.

“Our results suggest that the effects of placebo are not limited solely to sensory / nociceptive or cognitive / affective processes, but probably involve a combination of mechanisms that may differ according to the placebo paradigm and other individual factors -explains the specialist-. The study findings will also contribute to future research in the development of brain biomarkers that predict an individual’s responsiveness to placebo and help distinguish responses to placebo from pain relievers, which is a key goal of the new collaborative research center. , Treatment Expectation ”.

Understanding the neural systems that use and moderate responses to placebo has important implications for clinical care and drug development. The placebo responses could be used in a context, patient, and disease specific way. The placebo effect could also be used in conjunction with a drug, surgery, or other treatment, as it could potentially improve patient outcomes.