Vagus nerve

The vagus nerve, also called the tenth cranial nerve, starts in the brain and runs down the trunk of the body, with branches innervating the major organs. A major component of the autonomic nervous system and HPA axis, it interfaces with the parasympathetic nervous system and helps to regulate the heart, lungs, and the digestive system. It's a bi-directional nerve, meaning it both sends signals from the brain to the organs and the organs send messages back to the brain.

Function
The vagus nerve is an important sensor and regulator of basic functions including breathing, heart rate, the relaxation response, the gut-brain connection, and the formation of memories. The motor vagus nerve normally holds inhibitory influence over both systemic inflammation and the autonomic functions that become dysfunctional in POTS.

Immune system
Because it is a bidirectional nerve, both the afferent (sensory) and efferent (motor) branches have important functions: afferent pathways mediate anti-inflammatory responses via the HPA axis and the release of corticosteroids from the adrenal glands. Efferents pathways mediate anti-inflammatory processes via direct effects on immune cells or through the splenic sympathetic nerve. This system is called the cholinergic anti-inflammatory pathway (CAP).

For example, when the vagus nerve detects pro-inflammatory cytokines such as tumor necrosis factor-alpha or interleukin 1-beta, chemoreceptors in the afferent vagus nerve send a signal into the brainstem that triggers both glial cell activation within the central nervous system as well as the general innate immune response, sometimes called the sickness response. The efferent vagus nerve is responsible for an anti-inflammatory pathway. The vagus nerve speaks directly to the immune system via the neurotransmitter acetylcholine.

Vagus is thus important for maintaining homeostasis and preventing an overreactive immune response that can cause major injury or death. For example, vagus nerve stimulation is being used experimentally as an adjunct treatment for sepsis, which can cause death via a massive cytokine storm (e.g. Wang et al 2016 Int Rev Immunol).

Autonomic nervous system
Vagal tone is a measure of the constitutive output of the motor branch of the vagus nerve. It is frequently measured with the "tilt-table test" because the vagus nerve is responsible for the autonomic changes that allow us to go from lying down to standing up without fainting.

With a loss of vagal tone, both the antiinflammatory pathway and parasympathetic inhibition over autonomic systems are diminished. According to the vagus nerve infection hypothesis, exaggerated sensory vagus nerve signaling leads to loss of vagal tone and therefore a loss of control over inflammation and in some cases POTS.

Learn more

 * Dr. Diana Driscoll: Vagus Nerve and POTS/Mast Cell Activation, The Low Histamine Chef, January 12 2016
 * 9 Nervy Facts About the Vague Nerve, Mental Floss