Involvement of Transient Receptor Potential Ankyrin 1 (TRPA1) in Inflammatory Dental Pulp Pain

Abstract

TRPA1 is a cation channel involved in pain detection and inflammatory signaling in multiple cell types within the dental pulp. However, its role in pulpitis remains unclear. This study investigates the contribution of TRPA1 to dental pain and pain-like behaviors in a mouse model. Wild-type (WT) and TRPA1 knockout (KO) mice underwent pulp exposure, followed by multiple applications of either LPS or saline forming four experimental groups. Then pulp cap material placed. Pain-like behaviors were assessed on days 1, 3, and 7 post-op using the Nesting Test, Mouse Grimace Scale (MGS), and Von Frey Filament Test (VFF). Additionally, c-Fos expression in the trigeminal nucleus of the brainstem was quantified to assess neural activation. LPS administration in wild-type (WT) mice resulted in a significant increase in pain-like behaviors compared to TRPA1 knockout (KO) mice (p < 0.05), underscoring the role of TRPA1 in inflammatory pain responses. The most pronounced differences were observed between WT and KO groups under both LPS and saline treatment. However, differences between LPS and saline treatments within each genotype were minimal, and the absence of TRPA1 more substantially attenuated behavioral responses. Consistent with the behavioral data, c-Fos expression was significantly elevated in WT mice but markedly reduced in KO-LPS mice, indicating decreased neuronal activation in the trigeminal nucleus in the absence of TRPA1. These findings demonstrate that TRPA1 plays a critical role in activating the nociceptive dental pain and triggering pain like behaviors in mice. Further investigations are needed to explore the therapeutic potential of TRPA1 inhibition and its clinical applications for managing dental pain.