The Upregulation of AIM2 in the Central Nucleus of the Amygdala Correlates with Pain Induced by Tooth Movement

Pain is an unavoidable experience during orthodontic treatment. The central nucleus of the amygdala (CeA) plays a key role in regulating emotion and pain. Meanwhile, Absent in Melanoma 2 (AIM2) has been demonstrated in multiple neuroinflammatory and pain models for promoting inflammatory responses then enhancing nociceptive signaling. However, its role in pain caused by orthodontic tooth movement has not yet been clarified. In this study, C57BL/6J mice were used to establish an experimental tooth movement (ETM) model and were assigned to a control group, sham group, and experimental group. The face grooming and von Frey results showed that pain behaviors reached a peak on 1 d and returned to baseline levels by 7 d. After 14 days of continuous force application, mice developed obvious anxious behaviors and progressively worsened over time. The Western blot results revealed that tooth movement significantly increased AIM2 protein expression in the CeA. This was accompanied by a marked upregulation of NLRP3, caspase-1 and pp65. These findings suggest a potential role of NLRP3-NF-κB signaling in orthodontic tooth movement and also provide a new central target for the precise regulation of orthodontic pain.