Upregulation of transient receptor potential ankyrin 1 (TRPA1) but not transient receptor potential vanilloid 1 (TRPV1) during primary tooth carious progression.

OBJECTIVE: To quantify the changes in Transient Receptor Potential Ankyrin 1 (TRPA1) and Transient Receptor Potential Vanilloid 1 (TRPV1) expression throughout the process of inflammation induced by caries. METHODS: Forty primary teeth were obtained from children requiring dental extractions under local or general anesthesia. The teeth were grouped according to three stages reflecting the progression of dental caries: nine with intact dentin, 15 with exposed dentin (but not to the extent of the pulp), and 16 with exposed pulp. Immunofluorescence was used to validate the presence of dental pulp inflammation by demonstrating a decrease in NF-κB nuclear translocation. The expression levels of TRPA1 and TRPV1 were quantified in the pulp horn and the subodontoblastic and midcoronal regions of the pulp. RESULTS: The percentage of cells with NF-κB nuclear translocation was highest for teeth with intact dentin and decreased progressively during the progression of caries. TRPA1 expression was lowest in intact teeth and gradually increased as caries advanced. TRPV1 expression was similar in teeth with intact dentin, exposed dentin, and exposed pulp. CONCLUSION: The differences in TRPA1 and TRPV1 expression in response to caries suggest that these receptors play unique roles in the immune response during the progression of caries and that the pathophysiology of inflammation in the dental pulp varies between the early and late stages of caries.

Upregulation of TRPA1 and reduction of NF-κB translocation could be part of the immunomodulatory process during primary tooth inflammation.

Transient receptor potential ankyrin 1 (TRPA1) is expressed on neurons and immune and endothelial cells, and acts as a chemosensor that is activated by bacterial components and endotoxins. This study aimed to better understand how TRPA1 responds to inflammation induced by bacterial-related stimuli during dental caries. The pulp of 40 primary teeth and 46 permanent teeth were categorized into three stages of carious progression: intact dentin, exposed dentin and exposed pulp. We measured the percentages of cells with NF-κB nuclear translocation to verify the severity of inflammation, and then assessed TRPA1 expression by immunofluorescence technique in the pulpal horn, subodontoblastic and mid-coronal regions of the dental pulp samples at various stages of caries. We found NF-κB nuclear translocation gradually reduced during the progression of caries in all three areas of the dental pulp in both primary and permanent teeth. TRPA1 was gradually upregulated in the pulp of primary teeth as caries progressed, but did not significantly vary during caries in the pulp of permanent teeth. This study of TRPA1 expression demonstrates primary and permanent teeth exhibit distinct responses when undergoing carious infection.

Varied temporal expression patterns of trigeminal TRPA1 and TRPV1 and the neuropeptide CGRP during orthodontic force-induced pain.

OBJECTIVE: The aim of this study was to quantify the temporal changes in inflammation and TRPA1, TRPV1 and CGRP expression in the trigeminal ganglion during force-induced orthodontic pain. DESIGN: Orthodontic force was applied to both maxillary first molars in 8-week-old Wistar rats for 12 h, 24 h, 3 d or 7 d. The rat grimace scale (RGS) score and duration of face grooming were used to measure orthodontic pain. Western blotting was performed to assess TRPA1, TRPV1 and CGRP expression in trigeminal ganglia. NF-кB levels and colocalization of TRPA1, TRPV1 and CGRP were evaluated by immunofluorescent staining. RESULTS: Application of continuous force significantly increased pain behaviours at 1 and 3 d. NF-кB significantly increased in periodontal ligament at 12 h until 3 d. TRPV1 was significantly elevated within 1 d; TRPA1 significantly increased from 1-3 d; CGRP expression significantly increased from 12 h to 3 d. The TRPV1/TRPA1 expression ratio was highest at 12 h; the TRPA1/TRPV1 ratio peaked at 3 d. The percentages of trigeminal neurons co-expressing TRPA1/TRPV1, TRPA1/CGRP, and TRPV1/CGRP significantly increased by 12 h and peaked at 24 h. CGRP expression had a stronger positive correlation with TRPV1 than TRPA1. CONCLUSIONS: Inflammation induced by application of orthodontic force sensitizes trigeminal TRPV1 and TRPA1; TRPV1 is primarily activated as an early response, whereas TRPA1 is activated as a late response. Activation of both nociceptors results in CGRP release. Thus, blocking both TRPV1 and TRPA1 may represent a primary therapeutic target for relief of orthodontic pain.

Interval Vibration Reduces Orthodontic Pain Via a Mechanism Involving Down-regulation of TRPV1 and CGRP.

BACKGROUND/AIM: The transient receptor potential vanilloid 1 (TRPV1) ion receptor is involved in the release of calcitonin gene-related peptide (CGRP), a major contributor to orthodontic pain. Approaches that attenuate expression of TRPV1 and CGRP may reduce orthodontic pain. We explored the ability of high-frequency interval vibration to reduce orthodontic pain. MATERIALS AND METHODS: Orthodontic force (50 g) was applied to both maxillary first molars in 8-week-old Wistar rats (n=72). Vibration was applied at 125 Hz for 15 min/day. Duration of face grooming was assessed as a measure of orthodontic pain. Immunofluorescence and western blotting were used to assess TRPV1 and CGRP in the trigeminal ganglia. RESULTS: Compared to orthodontic force alone, application of vibration significantly decreased the duration of face grooming at 24 h and day 3 and reduced expression of TRPV1 and CGRP at 24 h. CONCLUSION: Vibration represents a promising mechanical approach to reduce orthodontic pain.