Objective To investigate the effect of intra-rACC( rostral anterior cingulate cortex,rACC) administration of Ifenprodil on aversion related to bone-cancer pain. Methods Totally 30 male Wistar rats without place preference were randomly divided into three groups: control group( n = 10),bone-cancer pain group( n = 10) and Ifenprodil group( n =10). A total of 3 μL MADB-106 cells( 4.8 ×109/mL) were inoculated into the right tibia bone marrow cavity in rats of the bone-cancer pain group and Ifenprodil group; rats of the control group were given the same dose of normal saline( NS). A total volume of 1. 2 μL Ifenprodil was administered into the rACC on the 14thday after operation,while the control group and bone-cancer pain group were given the same dose of NS. The diversity of the mechanical stimulation withdrawal threshold was measured using Von Frey stimulation on the 1stday before the operation,and the 3rd,7th,10th,12thand 14thday after the operation. On the 14thday after injection of Ifenprodil,the pain-related aversion in rats was observed. Results After the operation,the mechanical stimulation withdrawal threshold decreased obviously inrats of the bone-cancer pain group and Ifenprodil group from the 10thday to the 14thday( P 0. 05). Group comparison showed that the pain threshold to mechanical stimulation of rats in the bone-cancer pain group and Ifenprodil group decreased significantly compared with that of the control group by day 10th,12thand 14thafter inoculation with the tumor cells( P 0. 05). The residence time within chamber A was( 30 ± 4) % in bone-cancer pain group,lower than that of the( 52 ± 5) % in the control group( P 0. 05). After Ifenprodil treatment,the residence time within chamber A of the Ifenprodil group was( 42 ± 5) %,higher than that of the bone-cancer pain group,but still lower than that of the control group( P 0. 05). Conclusion Ifenprodil,a selective NR2B antagonist,administered into the rACC,can effectively alleviate pain-related aversion in rats with tibial bone cancer.