Overview of therapeutic applications of non-invasive vagus nerve stimulation: a motivation for novel treatments for systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder that commonly affects the skin, joints, kidneys, and central nervous system. Although great progress has been made over the years, patients still experience unfavorable secondary effects from medications, increased economic burden, and higher mortality rates compared to the general population. To alleviate these current problems, non-invasive, non-pharmacological interventions are being increasingly investigated. One such intervention is non-invasive vagus nerve stimulation, which promotes the upregulation of the cholinergic anti-inflammatory pathway that reduces the activation and production of pro-inflammatory cytokines and reactive oxygen species, culpable processes in autoimmune diseases such as SLE. This review first provides a background on the important contribution of the autonomic nervous system to the pathogenesis of SLE. The gross and structural anatomy of the vagus nerve and its contribution to the inflammatory response are described afterwards to provide a general understanding of the impact of stimulating the vagus nerve. Finally, an overview of current clinical applications of invasive and non-invasive vagus nerve stimulation for a variety of diseases, including those with similar symptoms to the ones in SLE, is presented and discussed. Overall, the review presents neuromodulation as a promising strategy to alleviate SLE symptoms and potentially reverse the disease.

The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases

“…In SLE, the scientific background that justifies the future use of VNS is depicted in [ 171 ]. Moreover, recently a double-blind sham-controlled pilot study was conducted on 18 SLE patients with pain, in which tVNS significantly reduced pain and fatigue, compared to sham-stimulation and joint scores after 5 and 12 days [ 172 ].…”

Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies

“…These autoimmune diseases show a dysfunction of the ANS that is mutually related to the increase of inflammation. The autonomic imbalance is related to an increased risk of developing cardiovascular disease, which is the major cause of morbidity and mortality in patients affected by autoimmune diseases [ 63 ]. More in general, ANS imbalance has been observed in immune-mediated inflammatory diseases (IMIDs), a descriptive term coined for a heterogeneous group of diseases that share common proinflammatory conditions, including not only autoimmune and inflammatory bowel disease, but also obesity, hypertension, chronic pulmonary disease, and coronary heart disease [ 64 ].…”

Control of inflammation using non-invasive neuromodulation: past, present and promise

“…This non-standard individualized approach, however, impedes the establishment of a standardized protocol. Other TA-VNS devices, NET-1000 and NET-2000, developed by Auri-Stim, have been approved by the FDA for the treatment of depression, anxiety and insomnia ( 87 ), but the effects on inflammation have yet to be established.…”