Could Focusing on Pain Actually Reduce Inflammation?

Can something as simple as directing attention toward a specific area of the body affect an inflammatory response taking place there? A study conducted at Bar-Ilan University’s Azrieli Faculty of Medicine in the Galilee and published in Nature Human Behaviour found that among healthy participants, focusing on sensations arising from an area of localized skin inflammation was associated with a smaller inflammatory response and a faster decline in inflammation.

The differences emerged within minutes and were observed in the vast majority of participants, even though the inflammatory stimulus they received was identical.

The study was conducted in the laboratory of Dr. Liron Rozenkrantz, head of the Psychobiology of Beliefs Laboratory at the Azrieli Faculty of Medicine in the Galilee. It was led by Nofar Mizrahi, then a doctoral student and now Dr. Mizrahi, in collaboration with Prof. Menachem Rotem, an expert in clinical immunology.

The Power of Attention

Dr. Rozenkrantz came to the research question through a field that has occupied her for years: the placebo effect.

“People receive a treatment that contains no pharmacological component, meaning there is no active ingredient that should help them, and yet they still improve,” she explains. “A person receives something that should not have an effect in itself, but expectations and the brain processes they trigger can influence the symptoms that person experiences. This has been extensively studied, and today we know quite a lot about the brain and physiological mechanisms involved. I find it fascinating.”

The placebo effect provided the starting point. From there, the researchers broadened their focus to examine the role cognition plays in different physiological processes.

“In my lab, we study how cognitive processes such as expectations and perceptions, as well as attention — where our mind is focused at any given moment — affect the biological regulation of the body,” says Dr. Rozenkrantz. “We wondered whether similar effects could occur through ordinary, everyday cognitive processes, outside the context of treatment or medication.”

The leap from the placebo effect to everyday life was explored through a cognitive process operating almost constantly: attention.

“We know that directing attention toward a sensation, for example pain after being injured, can increase the intensity of the pain we experience,” Dr. Rozenkrantz notes. “Often we do the opposite and distract ourselves from pain. If I stub my little toe on a piece of furniture and then open a news website, for example, it will hurt less. We also know that attention changes the way a sensation is represented in the brain, or that it is represented less intensely when we are distracted.”

“This led us to ask whether attention can affect not only how we experience a sensation, but also the biological process itself — in our case, the way the body regulates the immune response.”

From an Idea to the Laboratory

To answer this question, the researchers conducted a series of three experiments examining both the sensations reported by participants and the inflammatory response measured in their skin.

“A total of 57 people participated in the study,” says Dr. Rozenkrantz. “We conducted the main experiment twice, with two separate groups, in order to replicate the finding and better characterize the effect.”

The first experiment included 37 participants and the second included another 20. Most were women, ranging in age from 21 to 42. Seventeen participants from the first two groups returned for a third experiment designed to investigate the possible mechanisms underlying the effect.

To produce a consistent physiological response, the researchers used a histamine-based skin prick test.

“We induced localized inflammation in the participants’ skin using a standard procedure for producing acute inflammation in the arm,” Dr. Rozenkrantz explains. “A single drop of histamine is placed on the skin, followed by a superficial prick that allows it to penetrate.”

The inflammatory response develops within minutes, reaches its peak after approximately 15 to 20 minutes, and then begins to subside.

The next step was to isolate the effect of attention as much as possible.

“Each person came to the laboratory twice,” Dr. Rozenkrantz explains. “The conditions were identical on both occasions — the same time of day, the same inflammation — and the only thing that changed was what participants did with their attention during the 20 minutes in which the inflammation developed.”

The two sessions took place three to five days apart, and the order of the conditions varied among participants, allowing each participant to serve as their own control.

During both sessions, participants looked at a screen, but the target of their attention differed.

In one condition, attention was directed inward. “We instructed participants to pay attention to the sensations arising from the inflammation,” says Dr. Rozenkrantz. “They did not look at their arm, and of course they did not touch it. They looked at the screen, but directed their attention toward sensations coming from the inflamed area — itching and burning. It is unpleasant, but not unbearable.”

In the other condition, attention was directed away from the arm and toward the screen.

In the first experiment, participants watched neutral videos. In the second experiment, the comparison was made even more controlled.

“Everyone saw exactly the same thing on the screen,” Dr. Rozenkrantz explains. “The only difference was where their mind was focused — on sensations coming from the arm or on what they were seeing on the screen.”

In both conditions, participants viewed the same series of abstract shapes. In one condition, they were asked to focus on the shapes and consider whether they could exist in reality. In the other, the changing shapes served as reminders to redirect their attention back toward their arm. This allowed the researchers to isolate the effect of attention itself.

The Numbers Behind the Inflammation

As participants shifted their attention between their arm and the screen, the inflammatory response in the skin was systematically documented.

“We could clearly see the inflammation on the skin, which appeared as swelling and redness,” says Dr. Rozenkrantz. “Dr. Mizrahi monitored its development throughout the 20 minutes, measured it with a ruler, and photographed the area so that we could later verify the measurements.”

Measurements were taken six times: after 1, 3, 5, 10, 15, and 20 minutes. This produced two parallel records of the same inflammatory response for each participant — one while attention was directed toward the body and the other while attention was directed away from it.

Once all measurements had been collected, the researchers compared the two responses for each participant.

In the first experiment, approximately 90% of participants exhibited a larger inflammatory response during the distraction condition.

After 20 minutes, the average diameter of swelling was 3.5 mm when participants focused on their arm, compared with 5 mm during distraction. Redness was also smaller: 10.6 mm compared with 14 mm.

The differences began appearing within just three minutes and grew over the course of the experiment. In addition, among nearly 90% of participants, the inflammatory response stabilized or began to decline when attention was directed toward the inflamed area, compared with only 46% during the distraction condition.

The finding was replicated in the second group of participants.

“What surprised us most was how consistent the result was,” says Dr. Rozenkrantz. “For the vast majority of participants, attention affected the regulation of inflammation. When they focused on sensations coming from the inflamed area, they did experience the itching and burning more intensely, but the inflammatory response itself was smaller and subsided more quickly.”

“Our interpretation is that when the brain receives more information from the subjective sensation, it may be able to regulate the inflammation more effectively.”

The result effectively turned conventional intuition on its head: participants experienced more intense itching and burning, while their bodies produced a milder inflammatory response.

“There is a paradox here,” Dr. Rozenkrantz continues. “We might expect the body to deal with inflammation regardless of what we are thinking about it. The fact that we saw cognition participating in the regulation of inflammation led us to ask how this happens.”

What Happens When the Sensation Is Reduced?

To investigate this question, the researchers examined two possible, complementary pathways.

The first involved sensory information traveling from the inflamed area to the brain.

“The inflammation is the same inflammation, and the signal coming from the skin is the same signal,” Dr. Rozenkrantz explains. “What changes as a result of attention is the subjective experience and the way that experience is represented in the brain. We wanted to weaken the sensory signal and see whether that would affect regulation of the response.”

For the third experiment, lidocaine, a local anesthetic, was applied around the area where inflammation had been induced. Participants were asked to continue directing their attention toward the arm even though the sensations coming from it had been reduced.

“This allowed us to compare attention to the arm when the sensory signal was intact with attention to the arm when the signal was reduced by the anesthetic,” says Dr. Rozenkrantz. “We found that when less sensory information reached the brain, attention was less effective at regulating inflammation.”

However, the anesthetic weakened the effect of attention without eliminating it.

The inflammatory response while participants focused on their arm under lidocaine was larger than when they focused on the arm without anesthesia, but it was still smaller than during the distraction condition.

This suggested that another pathway might also be involved, one that does not depend solely on the strength of the signal coming from the skin.

A clue to this additional mechanism emerged from activity in the parasympathetic nervous system, which helps the body return to a state of balance and has also been associated with the regulation of inflammatory responses.

When participants directed their attention toward the arm, researchers measured greater heart rate variability, an indirect indicator of activity associated with the vagus nerve.

The vagus nerve is one of the major communication pathways between the brain and the body’s internal organs. It plays an important role in helping the body shift from heightened alertness toward relaxation, slowing the heart rate, and regulating inflammatory responses.

The difference remained even when sensations from the arm were reduced using lidocaine.

By contrast, the researchers found no differences in measures of sympathetic nervous system activity, stress, or arousal, suggesting that the effect was not simply the result of greater stress under one of the conditions.

Dr. Rozenkrantz emphasizes that this provides a clue to a potential mechanism rather than direct proof.

“We did not directly stimulate the vagus nerve,” she says. “What we saw was that activity associated with it appeared alongside inwardly directed attention, both when the sensory signal was intact and when the area was anesthetized, compared with the distraction condition.”

The study therefore points to two mechanisms that may operate in parallel: sensory information traveling from the inflamed area, and a top-down brain mechanism activating systems involved in regulating the body.

What Do the Findings Mean?

If simply changing where we direct our attention can alter an inflammatory response within minutes, it raises a much broader question: What role might everyday cognitive processes play in the way the body regulates itself?

“The significance is that an everyday, voluntary cognitive process — such as directing attention toward what is happening in the body or distracting ourselves from it — can influence the body’s biological regulation,” says Dr. Rozenkrantz. “In this case, we observed it in localized inflammation.”

The possibility that this effect extends beyond the immune system remains, for now, only a hypothesis.

“We think this may reflect a more general principle of how the brain works. We still do not know whether that is actually the case, but it is possible that one of the roles of cognition is to help the body regulate itself in response to the challenges it encounters.”

The finding also brings the research full circle, back to its starting point: the placebo effect.

“To me, this finding extends the phenomenon underlying the placebo effect into more everyday aspects of life,” says Dr. Rozenkrantz. “It raises the broader question of just how much cognitive processes can influence the body and participate in the way it regulates itself.”

However, there is still a long way to go from a controlled laboratory model to therapeutic applications.

“This opens up many research questions,” Dr. Rozenkrantz concludes. “When else does this happen? In which physiological systems beyond the immune system? Could we eventually harness this effect to help people with real injuries or after surgery? What happens in chronic processes? We still do not have answers regarding autoimmune diseases either.”

“We have identified several possible mechanisms, but there is still much more to investigate before we understand how attention produces this effect and how it might one day be used.”