Transcutaneous auricular vagus nerve stimulation and stress regulation: preclinical insights and unresolved challenges

Chronic stress exposure contributes to the onset and maintenance of a wide range of mental and physical disorders. Non-invasive modulation of vagal pathways has received increasing attention as a potential strategy for the prevention and treatment of stress-related conditions, given the central role of the vagus nerve in brain-body communication. By stimulating auricular vagal afferents, transcutaneous auricular vagal nerve stimulation (taVNS) is proposed to engage stress regulatory circuits, with downstream effects that may modulate stress-related physiology. Consistent with this mechanistic rationale, preclinical rodent research has begun investigating the effectiveness of taVNS as a non-invasive approach to mitigate stress-related outcomes. The aim of this narrative review is to summarize this emerging preclinical evidence, focusing on potential mechanisms involving central neural circuits implicated in stress regulation, as well as downstream autonomic function, inflammatory signaling pathways, and gut microbiota composition. Collectively, available studies support taVNS as a multi-system modulator of stress responses acting through interconnected neural, autonomic, immune, and gut-brain pathways. However, preclinical taVNS research remains at an early stage. Major unresolved challenges include the lack of standardized stimulation parameters and insufficient consideration of biological sex as a critical experimental variable. Addressing these limitations will be essential to improve reproducibility and strengthen translational relevance.