Pulpal Pressure Aggravates Pulpitis by Mechano-Inflammatory Signal Synergy

Pulpitis is a common oral disease characterized by severe pain and markedly impairs quality of life. A hallmark of its pathogenesis is a sharp increase in pulpal pressure due to vasodilation and oedema. However, the specific role of the elevated pulpal pressure in pulpitis progression remains unknown. This study aimed to investigate how pulpal pressure influences pulpitis progression and its underlying mechanism.

Rat models of pulpitis were established, and changes in pulpal pressure were quantified by immunofluorescence for mechanosensitive markers. Double immunofluorescence and colocalization analysis were used to assess the ability of macrophages to respond to pulpal pressure during pulpitis at 0, 24, 72 hours (n = 6/group/timepoint). Furthermore, an in vitro pressure-culture model of inflamed teeth was established at 0 and 180 kPa (n = 6/group), and pulp inflammation was assessed. An in vitro cellular model was established in which lipopolysaccharide-prestimulated macrophages were exposed to hydrostatic pressure. Finally, pulp inflammation after infiltration of a Piezo1 inhibitor was assessed by H&E and immunofluorescence.

Elevated pulpal pressure was positively correlated with pulpitis severity, and the capacity of macrophages to sense the pressure significantly increased with the progression of pulpitis (r = 0.672 ± 0.105 at 24 hours and 0.805 ± 0.077 at 72 hours, P < .001). Experimentally applied hydrostatic pressure significantly exacerbated both pulp inflammation and macrophage inflammatory responses (P < .05). Mechanistically, the synergistic interaction occur between signals induced by the inflammatory stimulus lipopolysaccharide and hydrostatic pressure in macrophages.

Elevated pulpal pressure synergized with inflammatory signals to exacerbate pulpitis. This mechano-inflammatory transduction pathway potentiated the TRAF6-NF-κB pathway and synergistically activated TRAF6-YAP pathway in macrophages, thereby leading to hyper-inflammatory activation and increased pulpitis.

Our work highlights the synergistic interplay between pulpal pressure and inflammation in disease progression, supporting a therapeutic strategy that integrates the mechanical microenvironment for effective inflammatory control.