Broader Explanation

Transcutaneous Vagus Nerve Stimulation

The process of stimulating the vagus nerve with micropulses of electrical current is referred to in various ways. Vagus nerve stimulation (VNS) typically refers to stimulation of the nerve with a surgically implanted device and electrode. Noninvasive, or transcutaneous, vagus nerve stimulation refers to stimulation of the vagus nerve without penetrating the skin using an external device and surface electrode. The vagus nerve provides unique access to the brain via its auricular branch, allowing it to modulate subcortical brain regions involved in neurophysiological and neuroinflammatory repair pathways.

The development of VNS as a therapy began with the research of James Corning, who developed the first fundamentally functional VNS device. In the late 1990s, the FDA approved its use after successful clinical trials for treatment-resistant epilepsy and depression. However, the adoption of VNS was limited by the need for surgical implantation, with geographical, severity-related, and financial constraints. Recent advances have made it possible to stimulate the vagus nerve without surgery, by using the auricular branch at the cymbal concha on the outer ear. This method activates vagal pathways similarly to surgical procedures, making it more accessible and cost-effective.

Why is stimulating the vagus nerve beneficial?

Vagus nerve stimulation utilizes various modulatory actions in the nervous, immune, autonomic, endocrine, cardiorespiratory, and gastrointestinal systems. The precise mechanisms of VNS action are still being theorized, but this has not hindered its ability to demonstrate safe and effective use for individuals with conditions related to vagal pathways.

Vagus nerve stimulation therapies have already been approved by regulatory agencies for applications such as mood enhancement, pain relief, sleep improvement, and anxiety reduction; studies are underway to assess their inflammatory modulation properties on the heart, as well as those exploiting the effects of neuroplasticity.

Vagus nerve stimulation - Mechanism of action

Autonomous modulation

The vagus nerve is the main nerve of the parasympathetic division of the autonomic nervous system, which regulates unconscious processes in the body. The vagus nerve innervates, among other things, all organs in the thoracic and abdominal cavities. The parasympathetic nervous system (PSN) is often referred to as the "rest and digest" system, while the sympathetic nervous system (SNS) is considered the "fight or flight" system. Stimulation of the vagus nerve has been shown to increase PSN activity and decrease SNS activity. Furthermore, through this regulation of metabolic homeostasis, the vagus nerve also regulates heart rate, with increased vagal activity being associated with a decrease in heart rate. This is important because autonomic dysfunction, as characterized by an overactive SNS response, is believed to underlie several high-impact chronic conditions, illustrating the value of an intervention that can modulate it.

Neurotransmitters

Neurotransmitters are chemical substances released by nerve fiber impulses into the areas surrounding this electrical activity. Examples of neurotransmitters include serotonin, norepinephrine/noradrenaline, and aminobutyric acid (GABA). Research in this area suggests that stimulating the vagus nerve can influence neurotransmitter release in the brain. Clinical studies indicate that VNS likely results in changes in serotonin (Ben-Menachem et al. 1995), norepinephrine (Krahl et al. 1998), GABA, and glutamate (Walker et al. 1999). These are all neurotransmitters implicated in the pathogenesis of major depression. It is thought that this influence on neurotransmitters, along with several other theoretical mechanisms, explains the mood-enhancing effects of vagus nerve stimulation.

Ignition modulation

It is now clear that the nervous system reflexively regulates the inflammatory response in real time, much in the same way it regulates heart rate and other vital functions. This is believed to occur via the vagus nerve, through a neural reflex mechanism known as the "inflammatory reflex." The brain receives signals from the immune system to optimally control inflammation in the body. However, dysfunction of these signals can lead to excessive inflammation. It was observed that without vagus nerve activity (whether due to vagotomy or neural lesions), there was an absence of the inflammatory reflex, resulting in excessive innate immune responses and cytokine toxicity (excessive inflammation). This led to clinical research and the demonstration that vagus nerve stimulation can lead to a decrease in inflammatory cytokines. The anti-inflammatory properties of (stimulating) the vagus nerve are believed to be mediated by the cholinergic anti-inflammatory pathway (CAP) and regulated by the hypothalamic-pituitary-adrenal (HPA) axis. These insights have led to new possibilities for treating inflammation via these selective and reversibly "hard-wired" neural systems.

Neuroplasticity

Research toward the end of the 20th century demonstrated that many aspects of the brain are changeable or "plastic," even in adults. Neuroplasticity is the brain's ability to restructure itself by generating new neural connections. It allows neurons, or nerve cells, in the brain to compensate for injury or disease and adapt their processes in response to new situations or environmental changes. The promotion of the neuroplastic effects of vagus nerve electrical stimulation through changes in neurotransmitter levels and/or processing in the central nervous system has led to increased focus on the use of transcutaneous vagus nerve electrical stimulation as a therapy for tinnitus and stroke rehabilitation. It is now theorized that a significant number of cases of tinnitus onset result from poor plasticity of the auditory cortex. These applications utilize the mechanisms of "targeted plasticity," stimulating the vagus nerve to promote neuroplasticity and pairing it with a specific stimulus—for example, sound therapy (for tinnitus) or rehabilitation exercises (for stroke recovery)—which targets this plasticity effect in the specific part of the brain associated with each condition. This has led to results such as accelerated and improved stroke recovery and reduced tinnitus symptoms.

The research below has contributed to our vision and treatment protocol:

1. https://pubmed.ncbi.nlm.nih.gov/10969939/

2. https://pubmed.ncbi.nlm.nih.gov/16133780/

3. https://pubmed.ncbi.nlm.nih.gov/27898202/

4. https://pubmed.ncbi.nlm.nih.gov/30217648/

5. https://www.frontiersin.org/journals/neuralcircuits/articles/10.3389/fncir.2017.00086/full

6. https://pubmed.ncbi.nlm.nih.gov/16690723/ 7. https://pubmed.ncbi.nlm.nih.gov/21907323/

8. https://pubmed.ncbi.nlm.nih.gov/12948617/

9. https://pubmed.ncbi.nlm.nih.gov/17125748/

10. https://pubmed.ncbi.nlm.nih.gov/27522167/

11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676495/

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020312/