Vagal neuropathies: An underrecognized potential driver of physical, mental, and immune symptoms

Peripheral neuropathies are widely recognized disorders of the peripheral nervous system. However, research and clinical attention have focused predominantly on somatosensory, somatic motor, and sympathetic neurons, with comparatively little emphasis on the vagus nerve. In this review, we propose a working definition of vagal neuropathies, referring to pathological alterations affecting vagal sensory and/or motor neurons. We synthesize evidence for vagal neuropathy across diverse human diseases and experimental models, examining structural, functional, and molecular hallmarks of nerve injury, associated clinical manifestations, and diagnostic challenges. Emphasis is placed on immune-neural interactions, given the central role of the vagus nerve in inflammatory reflexes and immunomodulation, and because immune and inflammatory mechanisms are implicated in the pathogenesis of many other neuropathies. Collectively, the literature suggests that vagal neuropathy is more prevalent than currently appreciated and may contribute to a broad spectrum of physical, mental, and immune dysfunctions. Recognizing vagal neuropathy as a distinct and clinically relevant entity has important implications for diagnosis, mechanistic understanding, and therapeutic development.