Background and Objective: It is well known that anti-nociceptive tolerance to opioids severely limits their clinical efficacy for the treatment of chronic pain syndromes. It has been reported that morphine-evoked neuro-inflammation is important in induction of morphine tolerance. According to the results of recent researches, the mitogen-activated protein (MAP) kinases are involved in the inflammation that is induced after repeated use of morphine. In this study, we aim to examine changes in the gene expression of the Erk1 and P38 MAP kinases in the prefrontal cortex (PFC) in morphine-tolerant rats. Method: Male Wistar rats were used in the current study. Two groups of animals received saline (1 ml/kg) or morphine (10 mg/kg) twice daily for 8 consecutive days. A hotplate test of analgesia was used to assess the induction of morphine tolerance on day 8 of the schedule. Two hours after the last injection on day 8, each rat was anesthetized, decapitated and the PFC was dissected on an ice-chilled surface. The gene expression of the Erk1 and P38 MAP kinase were examined using a real-time quantitative polymerase chain reaction (qPCR) method. Result: According to the results of the hotplate test, morphine treatment for 8 consecutive days induced anti-nociceptive tolerance to the opioid. The results of the real-time qPCR method for the gene expression of the Erk1MAP kinase in the PFC of the morphine-tolerant group showed a tendency to increase compared to the saline-treated control group but no significant change was observed. However, the results for the gene expression of the P38 MAP kinase in the morphine-tolerant group showed significant increase compared to the saline-treated control group (P<0.01). Conclusions: It can be concluded that morphine tolerance may induce neuro-inflammation, which may underlie, at least partly, the decreases in morphine-induced analgesia after repeated use of the opioid. It can be suggested that control of inflammation with specific drugs t
