Objectives <p>Pain is a common issue for individuals undergoing orthodontic treatment, with some even discontinuing treatment due to the pain experienced. Furthermore, orthodontic pain is often accompanied by negative emotional responses such as anxiety and unease. This study aims to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the mouse’s central nucleus of the amygdala (CeA), focusing on its involvement in nociception and anxiety during experimental orthodontic tooth movement (OTM).</p> Methods <p>Twenty-five 8-week-old male C57BL/6J mice were randomly divided into five groups: blank, 0 centinewton (cN), 10 cN, 30 cN, and 50 cN, based on the force applied for OTM(<i>n</i> = 5). Behavioral responses were assessed at different time points. Face-rubbing behavior and Von Frey test were used as a measure of nociception during experimental OTM. Both Open Field (OF) and Elevated Plus Maze (EPM) tests were conducted to evaluate anxiety-related behaviors. Immunohistochemistry was used to study the localization of TRPV1 in the CeA(<i>n</i> = 5), while Western blotting was employed to measure its expression levels(<i>n</i> = 3).</p> Results <p>During the experimental OTM, all groups of mice exhibited nociception, with the 50 cN group showing the highest level of face rubbing and the minimum force value of von frey test on the first day (1 d). Mice subjected to different force values also showed different degrees of anxiety-related behavior. The anxiety-related indexes in the 30 cN group and 50 cN group were significantly higher than in the 0 cN group on the 28 d (<i>P</i> &lt; 0.05). Immunofluorescence staining revealed that the TRPV1 expression in the 30 cN-1 d group was higher than in the 0 cN-1 d group (<i>P</i> &lt; 0.001). Western blotting analysis showed that the TRPV1 expression in the CeA of the 30 cN group was significantly higher compared to the 0 cN-1 d group during experimental OTM, reaching its peak on the 1 d and 28 d time point (<i>P</i> &lt; 0.001).</p> Conclusions <p>The present study demonstrates that orthodontic procedures can induce pain and emotional changes, which may be associated with increased TRPV1 expression in the central amygdala.</p> Clinical significance <p>The study provides preliminary evidence that TRPV1 in CeA is involved in both nociception and anxiety behavior during orthodontic tooth movement.</p>