Harnessing the Vagus Nerve: A New Frontier in Inflammation Control

The Vagus Nerve and Inflammation

Chronic inflammation underpins a wide range of health conditions, from autoimmune disorders and chronic pain to cardiovascular disease and depression. Emerging research points to the vagus nerve—a key component of the parasympathetic nervous system—as a powerful regulator of inflammation through what is termed the inflammatory reflex.

The recent study published in Scientific Reports by Ozaki et al. (2024) further elucidates the vagus nerve’s role in systemic inflammation, identifying mechanisms independent of the spleen, traditionally thought to be essential in this process. These findings could have profound implications for the use of vagus nerve stimulation (VNS) in managing inflammatory conditions.

Key Findings of the Study

1. Vagus Nerve Can Suppress Inflammation Without the Spleen

The research team conducted experiments on mice that had undergone splenectomy (spleen removal) and discovered that vagus nerve stimulation still reduced serum TNF-α, a key pro-inflammatory cytokine, during induced endotoxemia (a model of systemic inflammation). This challenges the long-held belief that the spleen is essential for the anti-inflammatory effects of vagus nerve signalling.

2. Neural Pathways Over Humoral Pathways

The team used cervical vagotomy (cutting the vagus nerve at the neck) and pharmacological inhibition of adrenergic receptors to show that the vagus nerve reduces inflammation via direct neural circuits rather than through circulating hormones or immune cells derived from the spleen.

3. Organ-Specific Anti-inflammatory Reflexes

In a surprising twist, the liver and gastrointestinal tract appeared to serve as alternative sites for vagus nerve-mediated immune modulation, suggesting that the vagus nerve can influence inflammation in a more decentralised and organ-specific manner.

Implications for Clinical Practice and Osteopathy

Expanding the Use of Vagus Nerve Stimulation (VNS)

VNS is already approved for treatment-resistant epilepsy and depression. This study provides new support for its use in managing rheumatoid arthritis, inflammatory bowel disease, and other chronic inflammatory disorders. A pivotal 2016 study by Koopman et al. showed that VNS significantly reduced disease severity in rheumatoid arthritis patients, aligning with the latest findings (Koopman et al., 2016).

Vagus Nerve and the Gut-Brain Axis

Given the vagus nerve’s central role in the gut-brain axis, its influence on gut-derived immune responses may explain why stress, diet, and lifestyle can so profoundly affect inflammation levels. Osteopathic care, which often includes strategies to modulate autonomic nervous system balance, may indirectly enhance vagal tone and thus contribute to inflammation control.

Lifestyle Interventions That Stimulate the Vagus Nerve

Patients may enhance vagal activity naturally through:

• Breathwork and diaphragmatic breathing

• Cold water immersion

• Meditation and mindfulness

• Regular aerobic exercise

• Manual therapies such as osteopathy and craniosacral therapy

Supporting Evidence from Other Studies

Several lines of research support the anti-inflammatory potential of the vagus nerve:

• Borovikova et al. (2000) first introduced the concept of the inflammatory reflex, showing that vagus nerve stimulation inhibited cytokine release during endotoxemia.

• Bonaz et al. (2016) reviewed the role of VNS in gastrointestinal inflammatory disorders and emphasised the vagus nerve’s capacity to downregulate immune responses.

• Tracey (2002) proposed the term “inflammatory reflex” and highlighted the nervous system's capacity to control immune function.

Together, these studies position the vagus nerve as a viable therapeutic target in systemic inflammation.

Conclusion: A New Era for Inflammation Control

The 2024 study by Ozaki et al. offers compelling evidence that the vagus nerve can suppress systemic inflammation independently of the spleen, operating through direct neural pathways. These findings not only advance our understanding of neuro-immune interactions but also support the expanding use of vagus nerve stimulation as a non-pharmacological intervention for inflammatory conditions.

Recommendation

For individuals suffering from chronic inflammation, autoimmune conditions, or unexplained fatigue and digestive issues, exploring ways to enhance vagal tone could offer meaningful relief. At Jo Martin Osteopathy, we support holistic, evidence-based approaches that harness the body's natural self-regulatory mechanisms. Patients are encouraged to consult with Dr. Jo Maehrlein to discuss how osteopathic care and lifestyle interventions may complement medical therapies and support vagus nerve function.

References

1. Bonaz, B., Picq, C., Sinniger, V., Mayol, J. F., & Clarençon, D. (2016). Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway. Neurogastroenterology & Motility, 28(2), 187–196.

2. Borovikova, L. V., Ivanova, S., Zhang, M., et al. (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405(6785), 458–462.

3. Koopman, F. A., Chavan, S. S., Miljko, S., et al. (2016). Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proceedings of the National Academy of Sciences, 113(29), 8284–8289.

4. Ozaki, T., Miyamae, M., Tanaka, Y., et al. (2024). The vagus nerve controls systemic inflammation independent of the spleen via a noncanonical neuroimmune pathway. Scientific Reports, 14, Article 9320. https://doi.org/10.1038/s41598-024-79687-3

5. Tracey, K. J. (2002). The inflammatory reflex. Nature, 420(6917), 853–859.