Technion: Researchers at the
Technion Faculty of Medicine have uncovered a potential course of action
of the placebo effect. The study, published in the journal Nature Medicine, indicates the effect of positive expectations on the immune system. For the first time, Technion researchers have indicated a
possible course of action of the placebo effect in the context of the
impact of an optimistic mindset on the operation of the immune system.
According to the findings, the brain’s “reward system” transmits
messages via the sympathetic nervous system that affect the immune
system’s efficiency.
The article, published in the prestigious journal Nature Medicine,
presents the work of Assistant Professor Asya Rolls from the Rappaport
Faculty of Medicine, carried out in cooperation with her colleague at
the Faculty, Assistant Professor Shai Shen-Orr. The study was led by
Tamar Ben-Shaanan, a doctoral student in the lab of Assistant Professor
Rolls.
Significant Applications
Photo: Haim Maggiore
“Our study explains how
areas of the brain associated with positive emotions can affect the
body’s coping with diseases,” explains Assistant Professor Rolls.
“Placebo is a complex phenomenon in which the patient’s expectation of
recovery affects his state of health. Expectation of improvement and
arousal of positive emotions are reflected in the activity of neurons in
the brain. Therefore we decided to understand, at the molecular level,
how areas of the brain associated with positive feelings affect the
functioning of the immune system, which is basically the body’s main
defense system. We have no doubt that an understanding the mechanisms
connecting the brain to this system could lead to significant medical
applications based on the effect of the mind on the body.”
We are all familiar with
the effect of the mind on the immune system. Sometimes mental stress
leads to poor physical condition, and sometimes a good mood alleviates
the sensation of pain. One of the most fascinating expressions of the
influence of one’s mental state on physical health is the
placebo-effect: the effect of sham treatment, for example a sugar pill,
on a person’s physical condition. Since this is an absolutely genuine
effect, the authorities now require the existence of a “placebo group”
in every drug approval process; since only with such a group is it
possible to determine the chemical and physiological effects of the test
drug on patients, disregarding the placebo effect. In this process it
turns out, in many cases, that the test drug is not more effective than
the placebo – both achieve improvements.
The research group of
Assistant Professor Rolls examined the effect of the “reward system” – a
brain region that is triggered in anticipation of a positive experience
and is also stimulated during the placebo effect. Using innovative
technological means, the researchers triggered the reward system in the
brains of mice and examined the behavior of the immune system following
this intervention. The findings show that triggering the reward system
stimulates the immune system, that is, causes it to operate more
effectively and eliminate bacteria more quickly. Moreover, as a result
of the intervention the immune system created a more robust immune
memory against the bacteria it was exposed to. In other words – it will
operate more effectively next time it is exposed to the same bacteria.
Innovative Technology
“Our breakthrough was made
possible thanks to two new technologies,” explains Assistant Professor
Shen-Orr. “One is DREADD technology, which enables precise activation of
specific neurons, and the second is CyTOF technology, which enables
high resolution characterization of hundreds of thousands of cells in
the immune system. By coupling these two technologies, we were able to
demonstrate a causal connection between the activation of specific
neural circuits in the brain and the increased activity of cell
populations in the immune system.
In the brain context, the
researchers focused on the ventral tegmental area (VTA), a key component
in the dopamine reward system. “This is the area of expectation for a
reward positive,” explains Assistant Professor Rolls, “and it is
stimulated, for example, when someone offers us a bar of chocolate.
Stimulation of this area, as we found, stimulates the immune system’s
anti-bacterial response, especially if stimulation occurs before
exposure to bacterial infection.
The researchers also mapped
the route through which the message passes from the brain to the immune
system; the sympathetic nervous system, which is responsible for
immediate response in emergency situations and stress. “This is the
system that dilates the pupils, accelerates the heartbeat and makes our
hair stand on end when we’re under stress. So it is no wonder that this
is the system through which the brain sends the immune system a message
to be on the ‘alert’ in the case of a bacterial infection, and even in
the case of a tumor. Now, as stated, it turns out that even the thought
or anticipation of something good or a reward, is able to stimulate this
system and increase the activity of the immune system.”
According to Assistant
Professor Rolls, this is the first scientific study conducted with an
experimental animal model, indicating the connection between the brain’s
dopamine activity and the immune system’s antibacterial activity. “This
study demonstrates that the immune system is NOT completely autonomous
and opens the possibility of stimulating it to act by a direct effect on
the brain. Understanding that stimulating the VTA in the brain triggers
the immune system will allow us to optimize existing therapies against
infections and boost the effectiveness of vaccines.”
An Evolutionary Advantage
This is how Assistant
Professor Rolls explains the effect of the brain on the immune system.
The brain sees the big picture of the body and its environment, and
therefore it can prioritize actions and direct the immune system.
“Moreover, such a connection between the reward system and the immune
system may have an evolutionary advantage. The reward system is
activated in situations such as a good meal and sex, situations that
expose us to bacteria and contaminants. Thus, it makes sense to couple
reward activation and infection. Moreover, if we enjoyed that activity
it is likely we will repeat it in the future and therefore it is in the
body’s interests to create a stronger immune memory against these
bacteria in order to overcome them next time.”