Abstract
OBJECTIVE: Vagus nerve stimulation (VNS) can inhibit inflammation in various diseases by activating the cholinergic anti-inflammatory pathway. However, whether VNS could attenuate periodontitis by activating α7-nicotinic acetylcholine receptor (α7-nAChR) remains unknown. METHODOLOGY: Ligature induction was utilized to establish the periodontitis rat model. Periodontal indices like bleeding, tooth mobility, and probing depth, were measured. Bone mineral density, trabecular thickness, and length of the cement-enamel junction to the alveolar bone crest were analyzed using micro-CT. Immunohistochemistry assessed bone morphology and inflammatory levels. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. For the in vitro inflammation model, RAW264.7 cells were stimulated with lipopolysaccharides and acetylcholine to study inflammatory responses. RESULTS: VNS significantly improved periodontal health and reduced alveolar bone loss in periodontitis rats. VNS alleviated inflammation by suppressing pro-inflammatory cytokines, including IL-1β, IL-6, and IL-18, enhanced bone formation, and activated the cholinergic anti-inflammatory pathway, as evidenced by increased α7-nAChR expression. Additionally, acetylcholine activation of α7-nAChR in RAW264.7 cells inhibited pro-inflammatory responses and promoted anti-inflammatory responses. CONCLUSION: These findings suggest that VNS can effectively reduce inflammation and improve periodontal outcomes in periodontitis.