Objective To observe the expression change of cyclooxygenase2 (COX2) in the trigeminal nucleus caudalis (Vc) in a rat model of experimental tooth movement pain (ETMP) and to determine its correlation with pain behavioral performance. Methods Adult male SpragueDawley rats were divided into ETMP group, Sham group and Naive group. Elastic rubber band was inserted between the incisor and the first maxillary molar bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. At different time points (0, 4h, 12h, 1d, 2d, 3d and 7d after rubber band insertion), the immunostaining and Western blot of COX2 were performed in each group after the detection of pain behavior. The inhibitors of COX2, COX1 or COX3 was injected intracisternally in ETMP group at 1d after rubber band insertion. After injection, pain behavior was immediately measured. Meanwhile, double labeling immunofluorescence of COX2 with NeuN or Fos was performed in Vc sections. Results Compared to Sham group and Naive group, the mouth wiping behaviour of ETMP group significantly increased at 4h after rubber band insertion, reached the highest value at 1 d (n=8/group; P＜0.05). The immunostaining and expression of COX2 was significantly increased in Vc of ETMP group (P＜0.05). The expression level of COX2 was found to be significantly correlated to the mouth wiping behaviour in ETMP group (P＜0.001, r=0.868). Intracisternal treatment with NS-398 (a selective COX2 inhibitor) exerted significant analgesic effect in ETMP group. However, intrathecal treatment with selective COX1 inhibitor and selective COX3 inhibitor had no effect on pain behavior. Double immunofluorescent staining showed all of the COX2 immunoreactive structures in Vc exhibited Neu Nimmunopositive staining and most of these COX2immunoreactive neurons were Fosimmunopositive. Conclusion The overexpression of COX2 contributes to tooth movement pain, and inhibiting Vc COX2 may represent a novel therapeutic strategy for clinical management of orthodontic pain.