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-kappa B 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-kappa B 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.

Automated summary

The study found that continuous orthodontic force significantly increased pain behaviors at 1 and 3 days, while NF-kappa B levels significantly increased from 12 hours to 3 days. TRPV1 significantly elevated within 1 day, TRPA1 increased from 1 to 3 days, and CGRP expression increased from 12 hours to 3 days. The activation of TRPV1 and TRPA1 sensitizes trigeminal neurons, leading to CGRP release.