TRPA1 triggers hyperalgesia and inflammation after tooth bleaching

Abstract

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

Chemical painful post-traumatic trigeminal neuropathy induced by dental bleaching: A case report

“…They activate TRPA1 expressed by neurons, which induces the release of SP and CGRP associated with neurogenic inflammation and a prolonged mechanical and thermal hypersensitivity state. More specifically, Chen et al (12) observed in pulp stem cells treated with a 15% hydrogen peroxide gel for 90 min or 40% for 45 min inducing oxidative stress and ROS production, an increase in the expression of TRPA1, intracellular absorption of Ca2+, activation of PANX1 favoring the secretion of ATP and its action as a neurotransmitter. In addition, TRPA1 upregulated TNF-ß and IL-6, inducing inflammation.…”

2-hydroxyethyl methacrylate-derived reactive oxygen species stimulate ATP release via TRPA1 in human dental pulp cells

“…The increase in extracellular ATP levels in the cells suggested the possibility of TRPA1 activation by ROS stimulation. Others demonstrated that TRPA1 antagonist HC-030031 suppressed H 2 O 2 production-induced intracellular ROS, ATP release, and the mRNA and protein levels of PANX1 32 . These finding suggest that ATP is released via PANX1 in response to TRPA1 channel activation by the H 2 O 2 -induced ROS stimulation.…”

“…Recent studies in rat incisor models of tooth bleaching have suggested that strong oxidative stress following treatment with high-dose H 2 O 2 induced ROS-mediated cytotoxicity in DPSCs, which could affect the hyperalgesia of tooth by regulating TRPA1 expression, intracellular Ca 2 + concentration, and ATP release into the extracellular space 32 , 34 . Moreover, oxidative stress in the periodontal tissue and dental pulp following orthodontic force is suggested to activate and/or mechanically sensitize TRPA1 on nociceptive fibers, resulting in orthodontic nociception 35 .…”

Effects on peripheral and central nervous system of key inflammatory intercellular signalling peptides and proteins in psoriasis

“…Activation of TRPA1 promotes intracellular calcium uptake, increases adenosine triphosphate (ATP) secretion, and induces inflammatory pain, whilst also upregulating the expression of TNFα and IL-6. 79 Therefore, the interaction between TRPA1 and TNFα collectively participates in the inflammatory response of psoriasis.…”