Cholinergic Pathway

A portable device delivering controlled electrical stimulation to the nervous system through the skin, without surgery. Designed for home or repeated use, these devices aim to make neuromodulation accessible outside clinical and hospital settings.

The longest cranial nerve (CN X), running as a paired structure from the brainstem through the neck, chest, and abdomen. It is the primary nerve of the parasympathetic nervous system and the main bidirectional communication pathway between the brain and internal organs.

A measure of the vagus nerve's baseline activity level, particularly in its regulation of heart rate and autonomic balance. Higher vagal tone is associated with better stress regulation, reduced inflammation, and greater physiological resilience.

A small cartilage flap at the entrance to the ear canal. Sometimes used as a stimulation site in vagus nerve research, its vagal innervation is more variable than the cymba conchae, which is considered the more reliable ear target for taVNS.

A major pro-inflammatory cytokine produced primarily by macrophages. Central to initiating and sustaining inflammatory responses, it is a key target of both the cholinergic anti-inflammatory pathway and several widely used anti-inflammatory drug therapies.

A non-invasive technique delivering mild electrical pulses to the outer ear — primarily the cymba conchae — to stimulate vagal nerve fibers without surgery. It is being studied as a potential treatment for inflammatory, neurological, and autonomic conditions.

Cytokines that initiate or amplify inflammatory responses, including TNF-α and IL-6. Essential for fighting infection, they are also implicated in tissue damage and disease when produced chronically or in excess of what the situation requires.

One of two main branches of the autonomic nervous system, responsible for rest, digestion, and recovery. The vagus nerve serves as its primary pathway to the heart, lungs, and digestive organs, transmitting both regulatory signals and sensory information.

A brainstem nucleus serving as the primary relay center for sensory signals carried by the vagus nerve. It processes visceral and autonomic information from organs throughout the chest and abdomen, and plays a central role in vagal signaling pathways.

Inflammatory processes occurring within the nervous system. Driven by activated immune cells in brain and spinal cord tissue and peripheral nerves, it is associated with multiple sclerosis, Alzheimer's disease, depression, and post-viral syndromes including Long Covid.

The targeted modulation of neural activity via electrical, chemical, or other stimuli. Applied to specific neural targets, it can influence pain, movement, autonomic function, and immune regulation without broadly affecting the nervous system.

The scientific field studying the interactions between the nervous system and immune system. It examines how neural activity influences immune responses and vice versa, forming the scientific foundation for bioelectronic medicine and vagus nerve stimulation research.

Versatile immune cells found throughout the body that engulf pathogens and dead cells, coordinate inflammatory responses, and produce cytokines including TNF-α and IL-6. They are key targets of the vagus nerve's cholinergic anti-inflammatory pathway.

A cytokine with both pro- and anti-inflammatory roles depending on context. Produced by immune and non-immune cells, it is widely elevated in chronic inflammatory and autoimmune diseases and is a commonly used biomarker of inflammatory activity.

A neural reflex arc in which the vagus nerve detects inflammation and the brain responds by activating efferent vagal signals that suppress excessive or dysregulated immune responses. Its discovery established the nervous system as an active regulator of immunity.

Signaling proteins released by immune cells to coordinate inflammatory responses. They include both pro-inflammatory types such as TNF-α, IL-6, and IL-1β, and anti-inflammatory types, playing roles in both protective immunity and chronic disease.

A potent pro-inflammatory cytokine produced primarily by macrophages. It triggers fever, inflammation, and immune cell activation, and is implicated in many autoimmune and inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease.

A protein with two distinct roles: inside cells it helps regulate gene expression; released into the bloodstream, it acts as an alarm signal that activates inflammation and pain. Elevated extracellular HMGB1 levels are associated with sepsis, autoimmune disease, and chronic inflammation.

The natural variation in time intervals between consecutive heartbeats. Higher HRV generally reflects greater parasympathetic activity and autonomic flexibility, and is widely used as an indirect measure of vagal tone, stress, and cardiovascular health.

A bidirectional communication network connecting the gastrointestinal tract and the central nervous system. It operates via neural, immune, endocrine, and microbial pathways, with the vagus nerve serving as the primary neural route.

Nerve fibers carrying signals from the brain to the body's organs and tissues. In the vagus nerve, efferent fibers transmit commands from the brainstem to regulate heart rate, digestion, and — through the cholinergic pathway — inflammatory responses.

A hollow in the upper outer ear. The only auricular region where the auricular branch of the vagus nerve (ABVN) is consistently present across all individuals, making it the preferred stimulation site for non-invasive vagus nerve stimulation (taVNS).

Inflammation that persists over weeks, months, or years rather than resolving after an acute trigger. Sometimes low-grade and symptom-poor, it is associated with cardiovascular disease, type 2 diabetes, autoimmune disorders, and neurological conditions.

A neurological process in which the central nervous system becomes persistently hypersensitive, amplifying pain signals. It underlies many chronic pain conditions where normal stimuli cause pain, or where pain persists well beyond the original injury.

An emerging medical field that uses targeted electrical stimulation of neural circuits to treat disease. Rather than systemic drugs, bioelectronic devices modulate specific nerve pathways to influence inflammation, pain, and organ function.

Found on macrophages and other immune and non-immune cells, this receptor mediates acetylcholine's anti-inflammatory effects. When activated by acetylcholine released by the vagus nerve, it inhibits the release of many inflammatory mediators including TNF-α and HMGB1.

The part of the nervous system controlling involuntary functions including heart rate, breathing, digestion, and stress responses. It consists of two main branches: the sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) systems.

Nerve fibers that carry sensory signals from the body to the brain. Approximately 80% of vagus nerve fibers are afferent, relaying continuous information from internal organs — including about inflammatory states — up to the brainstem.

A neurotransmitter used by the vagus nerve and other neural pathways to transmit signals between nerve cells and target tissues. In the context of inflammation, it is the key signaling molecule of the cholinergic anti-inflammatory pathway.

The only peripheral branch of the vagus nerve accessible through the outer ear. Its consistent presence in the cymba conchae — a small hollow in the upper outer ear — is what makes non-invasive, ear-based vagus nerve stimulation anatomically possible.