〔Abstract〕 Objective To investigate the effect of neuropathic pain on myocardial ischemia-perfusion injury in rats and the regulatory mechanism of AKT/mTOR signaling pathway involved in this process. Methods Forty-two Sprague-Dawley rats weighing 250-320 g(10 weeks old) were randomly divided into 3 groups(n=14): control group(group Con), myocardial ischemia-reperfusion injury group(group I/R) and neuropathic pain with myocardial ischemia-reperfusion injury group(group NP+I/R). The neuropathic pain model was prepared by the chronic constriction injury method(CCI) of the sciatic nerve. The mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL)of each group of rats were measured before and at 3, 7, and 14 days after the operation. The left anterior descending coronary artery is ligated for 30 minutes and opened for 120 minutes 14 days after the CCI operation to establish a model of myocardial ischemia-reperfusion injury. A slice of the heart was taken to detect the infarct size(IS) and area at risk(AAR) to calculate the myocardial infarction area. Western blot was used to detect the expression of AKT, mTOR and LC3 proteins, which was related to the AKT/mTOR signal pathway and autophagy. Results Compared with group I/R, MWT and TWL of group NP+I/R decreased at 3, 7, and 14 days after CCI.Compared with group Con, IS/AAR increased in group I/R, the ratio of p-AKT/AKT and p-mTOR/mTOR decreased, the ratio of LC3-Ⅱ/Ⅰincreased, and the differences were statistically significant(P<0.05). Compared with group I/R, IS/AAR decreased in group NP+I/R, the ratio of p-AKT/AKT and p-mTOR/mTOR increased, the ratio of LC3-Ⅱ/Ⅰ decreased, and the differences were statistically significant(P<0.05). Conclusion Neuropathic pain reduces myocardial ischemia-reperfusion injury in rats. The mechanism may be related to neuropathic pain regulating AKT/mTOR signaling pathway and inhibiting excessive autophagy.