Reconceptualizing regional anesthesia as a systemic modulator: a hypothesis-driven gut-brain axis perspective

Traditionally, regional anesthesia has been considered a local analgesic technique with benefits limited to the site of blockade. However, emerging preclinical and clinical evidence indicates that it may produce systemic effects by modulating the gut-brain axis. The gut-brain axis is a bidirectional regulatory system that integrates neural, immune, endocrine, and microbial signaling and is crucial for managing perioperative stress, inflammation, and physiological balance. This perspective article examines how regional anesthesia influences the gut-brain axis through several interconnected pathways, including neural modulation, immune regulation, endocrine effects, and indirect alterations in gut microbiota. We argue for reconceptualizing regional anesthesia as a systemic modulator and discuss its potential applications in perioperative recovery and chronic disease management. We conclude by calling for interdisciplinary research and mechanism-focused clinical trials to integrate this perspective into a more holistic model of perioperative medicine.