Vagal Modulation in Chronic Musculoskeletal Pain: Mechanisms, Clinical Implications, and Therapeutic Potential

Abstract Fibromyalgia and other chronic musculoskeletal pain conditions are increasingly recognized as disorders involving complex interactions among autonomic, inflammatory, metabolic, and neuropsychological systems. Emerging evidence identifies the vagus nerve as a key regulator in these processes due to its extensive bidirectional communication between the brain and visceral organs. This narrative review synthesizes current knowledge on the functional anatomy of the vagus nerve and its role in modulating pain pathways, immune responses, metabolic regulation, circadian rhythms, and gut–brain interactions. Vagus nerve dysfunction has been associated with heightened systemic inflammation, impaired descending pain inhibition, autonomic imbalance, and increased symptom severity in chronic pain conditions. Both invasive and noninvasive vagus nerve stimulation (VNS) techniques have demonstrated therapeutic potential across multiple clinical populations, including patients with fibromyalgia. Mechanistic studies suggest that VNS may reduce the release of pro-inflammatory cytokines, enhance parasympathetic tone, regulate neurotransmitter systems, and restore homeostatic autonomic function. Additionally, behavioral and mind–body interventions that enhance vagal activity – such as diaphragmatic breathing, meditation, and cognitive-behavioral strategies – may offer complementary benefits. While VNS represents a promising therapeutic approach, further large-scale, randomized controlled trials are required to determine long-term efficacy, optimal stimulation parameters, and patient-specific responsiveness. A deeper understanding of vagal mechanisms may ultimately support the development of more personalized and integrative approaches to chronic pain management.