The placebo analgesia response plays an important role in clinical practice, however, participants can be divided into placebo analgesia responder and non-responder. In a recent research, we found that there are also individual difference in placebo analgesia in animal research. In the present study, we use the previously animal model to study the mechanism uderlying placebo analgesia responder and non-responder. The dopamine level in prefrontal cortex (PFC) and nucleus accumbens (NAc) was measured to correlate with the placebo analgesia response. The methylation of catechol-O-methyltransferase (COMT) promoter in PFC and NAc was observed to determine the mechanism uderlying individual differences in DA concentration. Then, the μ opioid receptor in rostral anterior cingulate cortex (rACC) and cholecystokinin (CCK) receptor level in PFC were measured after the COMT inhibitor or the dopamine agonist was microinjected once or multiple times, which can reveal the mechanism of DA level on individual differences in placebo analgesia. In conclusion, this research will help to understand the mechanism underlying placebo responder and non-responder. Furthermore, this study will improve our ability to use of placebo analgesia in clinic. Therefore, the present experiment has important theoretical and practical value.