Focusing attention may help brain fight inflammation, study suggests

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When you feel pain or an itch, you might try to ignore it.

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But a fascinating new study has found that this may actually make your inflammation worse in certain situations.

The study, published in the journal Nature Human Behaviour, suggests that our brain and attention may change how our immune system responds to inflammation. When people tried to distract themselves from an itch, it caused the inflammation – as measured by redness and swelling of the skin – to grow larger in size and last longer than if they focused their attention on it.

The research adds to growing evidence that the brain and the immune system – long thought to be relatively separate and distinct from each other – actually have an intimate relationship. Dysfunctional immune activity and inflammation have been linked to several psychiatric and neurological disorders, including schizophrenia, depression, long COVID and dementia. In fact, recent research has found that our brains may trigger an immune response even from seeing someone who looks as though they might have an infectious condition.

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“The two systems are constantly in communication,” said Jonathan Kipnis, a professor of pathology and immunology at Washington University in St. Louis who studies neuroimmune interactions. The “brain is involved in the individual’s survival, and the immune system is involved in survival, and that’s what they do. So of course they talk to each other.”

In other words, the findings suggest that “what we think matters,” said Liron Rozenkrantz, a principal investigator in the Azrieli Faculty of Medicine of Bar-Ilan University in Israel and the study’s senior author.

In a clever set of experiments, Rozenkrantz and her colleagues caused inflammation on the forearms of 57 people – akin to “a bad mosquito bite,” she said – using a drop of histamine and the prick of a needle. Histamine is a chemical used by immune cells that triggers a reliable inflammatory response – that familiar itching, swelling and redness that anyone with an allergic reaction or mosquito bite knows well.

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In one experiment, researchers told people to stare at a screen and either distract themselves with a cognitive task on the screen or focus their attention internally on the sensations at the inflamed site (but without looking at it or touching it). Everything else stayed the same.

Crucially, the same people did the experiment twice, once with each condition.

When people directed their attention to the sensations of their inflamed skin, both the swelling and redness shrank more. By contrast, when the same people distracted themselves, 90 percent of them had more inflammation, with swelling and redness that were about 50 percent greater.

Paying attention to the inflammation also made it recover faster. After 20 minutes, almost 90 percent of people who paid attention had their swelling stabilize or diminish. When they were distracted, just 46 percent had improved inflammation.

These results suggest the extra input from the brain could be helping the immune system better regulate the inflammatory response.

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“It was striking to see the consistency of the effect and the fact that it was displayed across the vast majority of participants,” Rozenkrantz said.

There are at least two ways that the brain regulates inflammation, though Rozenkrantz said the mechanisms are not completely understood.

First, the inflamed sensations themselves seem to play a role. In a follow-up experiment, researchers covered people’s skin with lidocaine, a local anesthetic, after administering the histamine. With the sensations dulled, paying attention to the inflammation had a smaller effect on the itch – compared with the experiment without numbing cream. But the results were still better than distracting.

“By thinking about ‘This inflammation is hurting me,’ you’re actually ramping up the input of the inflammation to the nervous system, which in turn may be ramping up the output to turn it off,” said Kevin Tracey, president and chief executive of the Feinstein Institutes for Medical Research.

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The study also showed that when people paid attention to the inflamed site, they had more heart rate variability, a widely used proxy for increased parasympathetic activation – less “fight-or-flight” stress response and more “rest-and-digest” – and activity from the vagus nerve. The vagus nerve – which connects the brain to essential organs via 200,000 nerve fibres down either side of your neck – reduces inflammation when stimulated, Tracey discovered in earlier research.

“It’s a very reasonable hypothesis now that the stimulation of the vagus nerve somehow contributes to the decreased inflammation in the skin of the arm” in this experiment, said Tracey, who wrote “The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes.”

There are many remaining questions about the brain and immune system, including whether this study’s results mean anything clinically.

It’s not clear whether the brain was controlling the immune system because the study didn’t directly test for inflammatory cells or molecules, said Kipnis, who was not involved in the study but described it as done “really, really well.”

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Also, the study tested the effect of attention on short-lived inflammation when there was no pathogen present to fight. In follow-up research, Rozenkrantz will look at how attention changes our body’s response when it comes to chronic inflammation or fighting a pathogen.

After all, inflammation is not always bad.

“Inflammation is a good thing. It’s adaptive. We need it,” Rozenkrantz said. “It helps the tissue heal and sort of be separated from the other tissue and get the treatment it needs. But it’s also important the inflammation ends when its role is unnecessary anymore.”

The results may help explain some of the benefits of meditation known for centuries, Kipnis said. “Some mechanistic evidence is emerging, but we are just at the beginning of the journey to understand how these things work.”

This study also “makes you think differently about the placebo effect,” in which beliefs and expectations in the brain lead to biologically measurable changes in the body, Tracey said.

More practically, the fact that the brain may influence inflammation is not a call to eschew painkillers. But “when we find ourselves encountering an unpleasant sensation, maybe we can be more curious about it rather than just try to make it go away,” Rozenkrantz said.

Do you have a question about human behaviour or neuroscience? Email BrainMatters@washpost.com and we may answer it in a future column.

For more health news and content around diseases, conditions, wellness, healthy living, drugs, treatments and more, head to Healthing.ca – a member of the Postmedia Network.

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