In this study, using a transgenic approach to achieve the conditional ablation of nociceptors (marked as Nav1.8+ neurons), we found that nociceptors regulate early stages of the apical periodontitis initiation and progression by suppressing an initial immune response, which are seen as reduced influx of macrophages and lymphocytes and lower expression of IL-1⍺ and IL-6, promoting osteoblast differentiation and inhibiting osteoclast differentiation and its mediated resorption. The gene discussed is IL6; the disease is periapical periodontitis.