Vagus Nerve Stimulation in Physical Medicine and Rehabilitation: A Narrative Review of Pain, Inflammation, and Tissue Healing

Abstract Introduction: Vagus nerve stimulation (VNS) is a neuromodulatory intervention with systemic effects on inflammation, autonomic balance, and pain perception. While well established in neurology and rheumatology, its potential role in physical medicine and rehabilitation remains underexplored. Methods: We conducted a structured literature search in PubMed, Scopus, and Web of Science (2010–2025) focusing on VNS and rehabilitation-related outcomes. Eligible studies included preclinical and clinical research addressing pain modulation, inflammation control, musculoskeletal biology, wound healing, and functional recovery. Results: Preclinical studies consistently demonstrate suppression of pro-inflammatory cytokines and modulation of osteoblast/osteoclast activity through the cholinergic anti-inflammatory reflex. Clinical trials in rheumatoid arthritis show mixed results regarding cytokine suppression and disease activity. Pilot studies suggest that transcutaneous auricular VNS (taVNS) reduces perioperative and trauma-related pain and opioid use. Meta-analyses confirm modest analgesic benefits compared to sham stimulation. Reviews indicate potential contributions of VNS to wound repair and tissue perfusion. Evidence for effects on bone remodeling and implant integration is limited to animal models. To date, no dedicated trials have tested VNS in rehabilitation populations undergoing joint replacement or structured physical medicine interventions. Conclusion: Vagus nerve stimulation is biologically plausible and clinically promising as an adjunct in physical medicine and rehabilitation, with potential benefits for pain, inflammation, wound healing, and musculoskeletal recovery. Large, well-designed randomized controlled trials are required to establish its role in clinical rehabilitation pathways, especially in joint arthroplasty and chronic musculoskeletal pain populations.