Nerve stimulation promotes resolution of inflammation

Summary: Electrical stimulation of the vagus nerve promotes healing in people with acute inflammation by changing the balance between inflammatory and anti-inflammatory molecules.

Font: Karolinska Institute

The nervous system is known to communicate with the immune system and regulate inflammation in the body. Researchers at the Karolinska Institute in Sweden now show how electrical activation of a specific nerve can promote healing in acute inflammation.

The finding, published in the journal PNASopens new pathways to accelerate resolution of inflammation.

How the body regulates inflammation is only partially understood. Previous research by Peder Olofsson’s group at the Karolinska Institutet and other research groups has shown that electrical stimulation of the vagus nerve can reduce inflammation.

This nerve stimulation has been used with encouraging results in clinical studies of patients with inflammatory bowel disease and rheumatoid arthritis. However, it was not clear how nerve signals regulate the active resolution of inflammation.

“We have now studied the effects of signals between nerves and immune cells at the molecular level,” says April S. Caravaca, a researcher in Peder Olofsson’s group at the Department of Medicine, Solna, Karolinska Institutet and the Center for Bioelectronic Medicine at Stockholm at MedTechLabs. .

“A better understanding of these mechanisms will allow for more precise applications that harness the nervous system to regulate inflammation.”

The researchers showed that electrical stimulation of the vagus nerve in inflammation changes the balance between specialized inflammatory and anti-inflammatory molecules, promoting healing.

“Inflammation and its resolution play a key role in a wide range of common diseases, including autoimmune and cardiovascular diseases,” says Peder Olofsson.

“Our findings provide insight into how the nervous system can accelerate the resolution of inflammation by activating defined signaling pathways.”

Researchers will continue to study in more detail how nerves regulate the healing of inflammation. The image is in the public domain

Researchers will continue to study in more detail how nerves regulate the healing of inflammation.

“The vagus nerve is just one of many nerves that regulate the immune system. We will continue to map the neural networks that regulate inflammation at the molecular level and study how these signals are involved in disease development,” says Dr. Olofsson.

“We hope that this research will provide a better understanding of how pathological inflammation can be resolved and contribute to more effective treatments of many inflammatory diseases, such as atherosclerosis and rheumatism.”

Money: The study was supported by grants from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Heart-Lung Foundation, MedTechLabs, and Novo Nordisk. Peder Olofsson has shares in Emune AB. Co-author Jesmond Dalli is the founder and research director of Resolomics Ltd.

About this research news on brain stimulation and inflammation

Author: press office
Font: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is in the public domain.

original research: Closed access.
“Stimulation of the vagus nerve promotes the resolution of inflammation through a mechanism that involves Alox15 and requires the α7nAChR subunit” by April S. Caravaca et al. PNAS


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This shows the head and brain of a woman.

Vagus nerve stimulation promotes resolution of inflammation through a mechanism that involves Alox15 and requires the α7nAChR subunit

Unresolved inflammation underlies a variety of chronic inflammatory diseases, and therapeutic acceleration of inflammation resolution may improve outcomes.

Neural reflexes regulate the intensity of inflammation (for example, via signals in the vagus nerve), but whether vagus nerve activation promotes resolution of inflammation in vivo is unknown.

To investigate this, mice underwent electrical vagus nerve stimulation (VNS) or sham surgery at the cervical level followed by zymosan-induced peritonitis.

The duration of resolution of inflammation was significantly reduced and efferocytosis was significantly increased in VNS-treated mice compared to sham. Lipid mediator (LM) metabololipidomics revealed that VNS-treated mice had higher levels of specialized proresolving mediators (SPM), particularly the omega-3 docosahexaenoic (DHA) and docosapentaenoic (n-3 DPA) metabolomes, in peritoneal exudates.

VNS also shifted the ratio between proinflammatory and proresolving LM toward a proresolving profile, but this effect of VNS was reversed in mice deficient in 12/15-lipoxgenase (Alox15), a key enzyme in this SPM biosynthesis.

Significant VNS-mediated reduction in the number of neutrophils in peritoneal exudates was absent in mice deficient in the cholinergic subunit of the α7 nicotinic acetylcholine receptor (α7nAChR), an essential component of the inflammatory reflex.

Therefore, VNS increased local SPM levels and accelerated the resolution of inflammation in zymosan-induced peritonitis by a mechanism involving Alox15 and requiring the α7nAChR.

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