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.
“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.
“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.”