Vagus nerve stimulation in rheumatic diseases: linking autonomic nervous system regulation, inflammation, and clinical outcomes

Patients with autoimmune and inflammatory diseases most often exhibit sympathetic overactivity and dominance at the expense of the parasympathetic system, including the vagus nerve. It leads to dysfunction of the negative feedback mechanism within the hypothalamic–pituitary–adrenal axis, resulting in impaired regulation of cortisol levels, stress responses, and pro-inflammatory cytokines. Furthermore, vagal dysfunction affects the mechanism by which acetylcholine binds to α7 nicotinic receptors on macrophage surfaces, thereby inhibiting the release of TNF-α and other pro-inflammatory cytokines. The aim of this review was to identify reports elucidating the mechanisms underlying the anti-inflammatory effects of the vagus nerve and to evaluate the efficacy of VNS as a potential method for modulating autonomic nervous system function. A literature search was conducted using the electronic databases PubMed, focusing on the role of the vagus nerve in autoimmune disorders, and on vagus nerve stimulation (VNS). Based on the collected data, a reduction in inflammatory activity and decreased production of pro-inflammatory cytokines were observed following vagus nerve stimulation. Moreover, the authors of the studies analyzed reported additional therapeutic effects, including pain modulation, suppression of disease activity, and a reduction in fatigue. Vagus nerve stimulation represents a promising alternative therapeutic modality for the treatment of rheumatologic diseases. However, further high-quality studies conducted in substantially larger cohorts are required, taking into account variability in stimulation parameters and their differential impact on clinical outcomes.