The Role of the Vagus Nerve and Its Stimulation in Modulating Inflammatory Skin Diseases and Other Dermatologic Conditions: From Mechanisms to Therapeutics.

BACKGROUND: Inflammatory skin diseases typically exhibit autonomic imbalance characterized by sympathetic dominance and parasympathetic hypofunction. The vagus nerve plays a fundamental role in modulating inflammatory responses through the cholinergic anti-inflammatory pathway, a neural circuit in which vagal efferent signals lead to acetylcholine release that suppresses pro-inflammatory cytokine production, and hypothalamic-pituitary-adrenal axis (HPA).

SUMMARY: This review analyzes emerging evidence supporting vagus nerve stimulation (VNS) as a therapeutic approach for inflammatory skin diseases. We reviewed preclinical studies and published clinical reports examining the effects of invasive and non-invasive VNS on inflammatory skin conditions and associated biomarkers. Recent research demonstrates that VNS can reset a dysregulated HPA axis and reduces inflammatory cascades by inhibiting inflammasome activation, attenuating pro-inflammatory cytokine synthesis, and accelerating inflammation resolution. Preclinical studies show that both invasive and non-invasive VNS significantly attenuate inflammatory markers in mouse models of psoriasis, eczema, and vitiligo, despite the skin lacking direct vagal innervation. Published reports document notable improvement in seborrheic dermatitis and rosacea following transcutaneous VNS. Inflammatory skin diseases share similar comorbidity profiles with conditions directly linked to vagal dysregulation, suggesting a common pathophysiological framework defined by impaired neuroimmune communication. The "Cutaneous Vagal Dysregulation Inflammatory Axis" views inflammatory skin disorders as resulting from a bidirectional relationship in which autonomic imbalance promotes a pro-inflammatory state across multiple organ systems.