Vital pulp therapy has been a widely adopted for managing pulp diseases, in which the control of pulpitis progression is critical. Although the transient receptor potential ankyrin 1 (TRPA1) channel mediates pain transduction and inflammatory responses, its specific role in pyroptosis during pulpitis remains poorly understood. Pulp inflammation was evaluated using H&E staining for group stratification. The expression and localization of TRPA1 and pyroptosis-related markers (NLRP3, cleaved caspase-1, and IL-1β) were assessed by immunohistochemistry. Additionally, qRT‒PCR and Western blotting were performed to analyse the expression levels of TRPA1 and pyroptosis markers in vitro. Mitochondrial function was evaluated by flow cytometric analysis of the mitochondrial membrane potential (ΔΨm) and calcium influx. Simultaneously, intracellular and mitochondrial reactive oxygen species (ROS) levels were measured using fluorescence staining. TRPA1 was predominantly expressed in the fibroblast-rich zone and odontoblastic layer in the dental pulp, and its expression levels were positively correlated with pulp inflammation severity. In vitro, lipopolysaccharide (LPS) stimulation significantly increased the expression of pyroptosis-related markers and induced mitochondrial dysfunction, as evidenced by ΔΨm depolarization, intracellular Ca2+ overload, and excessive reactive oxygen species (ROS) generation. Notably, the pharmacological inhibition of the TRPA1 channel markedly attenuated these pathological changes, reducing pyroptosis-related markers responses and ameliorating mitochondrial impairment in human dental pulp cells (hDPCs). During pulpitis, the expression of the TRPA1 channel was positively correlated with the severity of inflammation and pyroptosis-associated molecular signalling in dental pulp tissue. These findings suggest that TRPA1 may mediate mitochondrial damage through calcium ion influx, subsequently promoting cell pyroptosis in the context of pulpitis. These findings highlight a potential link between TRPA1 activation and mitochondrial dysfunction, warranting further investigation into the underlying mechanisms .
Huang et al. (Sat,) studied this question.