Background: Apelin has recently been identified as an analgesic agent and a novel neuropeptide. On the other hand, it has been shown that exercise can lead to reduced pain in morphine-dependent patients. Objectives: Therefore, the aim of this study was to evaluate apelin and pain threshold changes in healthy and morphine-dependent rats in response to two exercise paradigms. Materials and Methods: In this study, 30 healthy and 30 morphine-dependent rats were used. Morphine-dependent and healthy rats were divided into six groups: 1, a control (healthy) group; 2, a healthy endurance group; 3, a healthy strength-training group; 4, an addicted control group; 5, an addicted endurance group; 6, an addicted strength-training group. Then, the training groups performed aerobic and strength training for eight weeks. After the training program, the tail flick and formalin tests were used to assess pain. Apelin was also measured by ELISA. Results: Regardless of the type of exercise, exercise significantly increased the apelin serum levels in healthy rats. The apelin levels significantly increased in the morphine-dependent rats compared with the healthy control group. Endurance, unlike strength training, significantly increased apelin in the serum compared to the addicted control group. The training led to pain relief in the morphine-dependent rats and returned it to the healthy control group level. The Pearson correlation showed a reverse significant correlation between the serum apelin level and the tail flick test in the morphine-dependent rats. Conclusions: The results showed that endurance training reduced pain by increasing apelin in morphine-dependent rats. Therefore, it is suggested that this type of training be considered for the morphine-dependent patients for pain relief.
