Objective To investigate the phenomenon of hippocampal ferroptosis and its change in a rat model of chronic constriction injury（CCI） of the sciatic nerve，as well as the association between hippocampal ferroptosis and emotional disorders induced by neuropathic pain. Methods A total of 32 male Sprague-Dawley rats were randomly divided into Sham group，CCI group，CCI+F group，and CCI+E group，with 8 rats in each group. The rats in the CCI+F group and the CCI+E group were given intraperitoneal injection of Ferrostatin-1（10 mg/kg） and Erastin（10 mg/kg），respectively，since day 7 after surgery for two consecutive days. Mechanical withdrawal threshold（MWT），paw withdrawal latency（PWL），and open field test（OFT） were measured before surgery and on days 7 and 14 after surgery. On day 14 after surgery，the rats were sacrificed to collect hippocampal tissue；Western blot was used to measure the levels of GPX4，xCT，and FTH1；related kits were used to measure the expression levels of MDA and GSH；HE staining，Nissl staining，and immunofluorescent staining were performed；transmission electron microscopy was used to observe the structural changes of the mitochondria. Results In terms of behavioristics，compared with the Sham group，the CCI group had significant reductions in MWT and PWL on day 7 after surgery（P<0.001），with further reductions from day 7 to day 14 after surgery（P<0.001）；compared with the CCI group，the CCI+F group had significant increases in MWT and PWL on day 14 after surgery（P<0.001），and the CCI+E group had no significant change in MWT and a significant reduction in PWL（P<0.01）. In terms of the OFT test，compared with the Sham group，the CCI group had significant reductions in total distance and number of central squares crossed （P<0.001） and a significant increase in immobility time（P<0.001）；compared with the CCI group，the CCI+F group had significant increases in total distance and number of central squares crossed and a significant reduction in immobility time，while the CCI+E group had no significant changes in these indices. In terms of biochemical results，compared with the Sham group，the CCI group had significant reductions in GPX4，xCT，and FTH1（P<0.01），a significant increase in MDA，and a significant reduction in GSH；compared with the CCI group，the CCI+F group had significant increases in GPX4，xCT，and FTH1（P<0.05），a significant reduction in MDA（P<0.001），and a significant increase in GSH（P<0.01），and the CCI+E group had significant reductions in xCT and FTH1，with no significant changes in MDA and GSH. In terms of morphology，compared with the Sham group，the CCI group had damage and necrosis of hippocampal neurons，significant reductions in Nissl bodies and c-Fos level（P<0.05），and significantly damaged mitochondrial cristae on day 14 after surgery；compared with the CCI group，the CCI+F group had intact structures of hippocampal neurons，significant increases in Nissl bodies and c-Fos（P<0.05），and relatively intact mitochondria，while there were no significant differences in c-Fos and Nissl bodies between the CCI+E group and the CCI group. The pairwise linear correlation analysis of PWL，MWT，GPX4，OFT，and c-Fos on day 14 after surgery showed a significantly positive correlation between any two indicators（P<0.01）. Conclusion Peripheral nerve injury triggers ferroptosis in the hippocampus and causes anxiety and depression，thereby aggravating ferroptosis and accelerating the development of central hyperalgesia.