Conditioned reaction: Anyone suffering from an allergy can get complaints without pollen, house dust and the like. The blame is the nocebo effect – the negative variant of the placebo effect. According to an experiment with hay fever patients, a key stimulus or a specific location can be sufficient to trigger an allergic reaction without any allergen. However, there are differences.
Usually people with hay fever, asthma or another allergic disease only have problems if they come into contact with the allergy trigger – whether pollen, house dust or even a food. The immune system sensitized to these allergens then releases antibodies and messenger substances that cause the typical symptoms.
Allergy reaction without allergen
But there is another way: As early as 1886, a doctor reported a woman who already had an asthma attack when she saw an artificial rose. Since then, several studies have demonstrated that allergy sufferers can show a conditioned reaction to certain key stimuli: their immune system triggers an allergy attack if they experience a stimulus associated with experiences with the allergy triggers – even if there is no allergen.
With such a negative reaction, psychologists and medical doctors speak of a nocebo effect without a real trigger. Conversely, an active ingredient-free placebo, declared as an antiallergic, can have a soothing placebo effect. “These observations underline the importance of psychological factors in allergic diseases,” said Luciana Besedovsky from the University of Tübingen and her colleagues.
Nasal spray for hay fever sufferers
But how far does the power of the psyche go? To find out, the researchers examined whether the mere context – the spatial environment – is sufficient for the allergic nocebo effect. To do this, they asked 25 patients with colds in the evening in a test room. All received a dose of their allergen via nasal spray, to which a fragrance was added as a key stimulus. As expected, an allergic reaction occurred, as evidenced by the increase in the marker enzyme tryptase in the nasal mucosa.
Half of the subjects then went to sleep for eight hours, the second half had to stay awake until the following evening. The actual test, however, followed a week later: Again, the test subjects were asked to enter the test room, where they received the scented nasal spray again after a short wait. But this time without allergens.
Response to key stimulus – and the environment
The result: The test subjects’ immune system reacted to the pseudo-nasal spray, as evidenced by increasing enzyme concentrations in their nasal mucosa. This reaction also occurred in a supplementary test when the nasal spray was administered in a different environment, as the researchers report. This confirms that a key stimulus can trigger the reaction, in this case in the form of the fragrance.
The interesting thing, however, was that this reaction not only occurred when the key stimulus was present, but also when you looked at the test room. “Some of the test subjects reacted with an allergic runny nose shortly after entering the test room,” reports Besedovsky. “This shows that an allergic reaction can be triggered not only by specific stimuli, but also by returning to the environment in which one previously encountered the allergen.” This is the first evidence of such context-dependent conditioning.
“It’s amazing how quickly the immune system learns the mismatched response. In the experiment, a single allergen dose was enough to link the allergic reaction to the environment, ”says Besedovsky.
Sleep is essential
However, there was a crucial difference: While the key stimulus of the scented nasal spray worked in all test groups and environments, only the “sleepers” reacted to the environment. However, those who were not allowed to sleep after the first round did not. “As with many classic learning processes, the sleep phase played a crucial role in our study. This is the only way the brain can link a specific environment to an allergic reaction, ”says senior author Jan Born.
But why? The researchers explain this by saying that the hippocampus plays an important role in learning context-dependent behavior. This center of our brain, which is important for the memory, sorts the experiences during sleep and transfers them to long-term memory. In the evolutionarily older reaction to key stimuli, on the other hand, learning takes place without sleep and hippocampus involvement. (Proceedings of the National Academy of Sciences, 2020; doi: 10.1073 / pnas.1920564117)
Source: Eberhard Karls University of Tübingen
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