Objective: To investigate the anxiety-like behaviors associated with pain sensitivity in mice induced by the injection of complete Freuder"s adjuvant (CFA), and to explore the changes in the expression levels of glutamate receptor subtype 2 (GluR2) and GLUR2-P in the cingulate cortex (RSG) of mice. Methods: Twenty-six male C57BL/6 mice aged 10-12 weeks, weighing 20-25g, were selected as the experimental subjects. The mice were randomly divided into the control group (Sham group) and the experimental group (CFA group), with 13 mice in each group. In the Sham group, 25μl of normal saline was injected into the right sole of the foot at one time as the negative control for modeling. The CFA group was modeled by a one-time injection of 25μl of Complete Freund"s adjuvant (CFA) on the right sole of the foot. On the 0th day (before CFA modeling), the 1st day (2 hours after modeling), the 3rd day, and the 7th day respectively, the foot contraction rates of both left and right feet were detected to determine the success of CFA modeling and to measure the mechanical pain threshold of mice. The open field test was conducted to determine the anxiety of mice. The RSG brain region specimens of mice modeled for 7 days were selected, and the expression levels of GluR2 and GLUR2-P were detected by western blot and immunohistochemistry respectively. Results: On the 1st, 3rd, and 7th days, the foot contraction rate of mice on the same side in the CFA group was significantly higher than that in the Sham group on the same side (p<0.05). The time that mice in the CFA group stayed in the central area and the number of times they passed the central platform were significantly lower than those in the Sham group (p<0.05), but there was no significant difference in the total distance they ran between the two groups. Seven days after CFA injection, the western blot results showed that there was no significant difference in the total protein content of GluR2 in the RSG brain region between the CFA group mice and the Sham group. However, the content of GluR2 phosphorylation in the contralateral brain region of the CFA group mice was significantly higher than that of the contralateral brain region of the Sham group (p<0.05). The immunohistochemical results showed that the GluR2-p in the contralateral brain region of the CFA group was significantly increased compared with that of the contralateral brain region of the Sham group (p<0.05), and also significantly increased compared with the same side of the individual (p<0.05). Conclusion: CFA injection triggers pain sensitivity accompanied by anxiety-like behaviors and leads to an increase in GluR2 phosphorylation in the RSG brain regions of mice, which may be involved in the pathological process of anxiety-like behaviors.