Objective To explore the temporal characteristics of anxiety-like emotions induced in the hyperalgesia priming rat model and the excitability changes in the anterior cingulate cortex (ACC) via dynamically observing the paw withdrawal thresholds ( PWTs ), anxiety-like behaviors, and immediate early gene ( c-Fos ) and paralbumin (PV) expression in the bilateral ACC at different time points. Methods The experimental rats were randomly divided into the sham hyperalgesic priming (SHP) group and the hyperalgesic priming (HP) group. In the HP group, 100 μL of 1% λ-carrageenan (Car) was subcutaneously injected into the left hind plantar ( first time), and after the PWT returned to the basic level, 25 μL of prostaglandin E₂(PGE₂ ) (100 ng) was injected into the left dorsum ( second time). In the SHP group, an equivalent volume of saline was injected (first time), and the same volume of PGE₂ was then injected (second time). We measured the PWT of the hyperalgesia priming rat model before modeling (base), and at 4, 24, 48, 72 h, and 10 d after Car injection, and at 1, 4, 24, 48, 72 h, 7 d, and 14 d after PGE₂ injection. Anxiety-like behaviors were observed in an open field (OF) at 24 h, 7 d, and 14 d after PGE₂ injection, in an elevated zero maze (EZM) at 24 h, 8d, and 15 d after PGE₂ injection. Immunofluorescence was used to detect the expression changes in c-Fos and PV-positive cells in the bilateral ACC. Results Compared with the SHP group, the PWTs of the HP group were significantly reduced at 4, 24, 48, and 72 h after Car injection (P< 0. 01) and recovered to the basic level at 10 d after Car injection (P> 0. 05); whereas, the PWTs significantly decreased at 4 h after PGE₂ injection and remained low for 14 days (P< 0.01). Compared with the SHP group, the total distance, the distance in the central area, the time in the central area, and the number of central zone entries in the OF of the HP group were significantly reduced at 24 h after PGE₂ injection (P<0.05). The total distance, the distance in the open arm, the time in the open arm, and the number of open arm entries in the EZM of the HP group were significantly reduced compared with the SHP ( P< 0.05). Interesting, there was no significant difference in anxiety-like behaviors in the OF and EZM at 7 d (or 8 d) and 14 d (or 15 d) after PGE₂ injection between the SHP and HP groups (P> 0.05). Compared with the SHP group, c-Fos positive expression in the bilateral ACC of the HP group was significantly decreased at 10 d after Car injection, while it was significantly increased at 24 h and 8 d after PGE₂ injection (P< 0.01), but there was no significant difference at 4 h and 15 d after PGE₂ injection (P>0.05). There was no significant difference in PV-positive expression in the bilateral ACC at 10 d after Car injection and 4 h, 24 h, and 8 d after PGE₂ injection (P> 0.05). PV-positive expression on the ipsilateral side of the HP group was significantly decreased at 15 d after PGE₂ injection compared with that of the SHP group (P< 0.01). Conclusions The hyperalgesia state in the hyperalgesia priming rat model can last for more than 14 days, accompanied by transient stress anxiety-like behaviors; however, it is not easy to induce persistent anxiety-like behaviors. The ACC excitability was in a state of compensatory inhibition before the transition, but was enhanced after the transition, characterized by increasing c-Fos expression in the early transition stage and decreasing PV expression in the later stage.