Vagus Nerve Stimulation (VNS)

Cholinergic anti-inflammatory reflex mechanism: vagal stimulation releases acetylcholine in the spleen, where it activates α7-nicotinic receptors on macrophages, inhibiting their production of TNF-α and IL-6. It is a direct parasympathetic control over systemic inflammation — an evolutionary mechanism little appreciated until Tracey's work in the 2000s.

Approved or investigated clinical applications:

Approved: drug-refractory epilepsy, treatment-refractory depression, cluster migraine (gammaCore). Under investigation: rheumatoid arthritis (Koopman 2016 studies with implantable VNS showed significant disease activity reduction), Crohn's disease, fibromyalgia, tinnitus, cognitive impairment, post-stroke recovery, post-COVID depression, long COVID.

Accessible techniques (do not require medical device): Breathing 4-6 bpm (heart coherence): 5-15 min/day robustly activates vagal tone. Cold exposure on face and neck: cold water on face stimulates the mammalian diving reflex, strongly vagotonic. Singing and humming: activates laryngeal muscles innervated by the vagus. Auricular stimulation: TENS of 1-100 Hz on cymba conchae (auricular branch of vagus). Yoga and pranayama: especially ujjayi and bhramari breathing.

Monitoring of vagal tone: HRV — especially RMSSD, a metric directly proportional to night-time parasympathetic activity. Vagal training is evidenced by consistent HRV increases over weeks/months.