前扣带皮层吻侧部注射NR2B受体阻断剂Ifenprodil对骨癌痛大鼠伴随痛厌恶情绪体验的影响

Effect of Ifenprodil administered into the rostral anterior cingulate cortex on the pain-related aversion in rats with bone-cancer pain

目的探讨前扣带皮层吻侧部(rACC)内注射N-甲基-D-天门冬氨酸受体2B亚基(NR2B)受体阻断剂Ifenprodil是否减轻骨癌痛大鼠伴随的痛厌恶情绪体验。方法无位置偏爱的雄性Wistar大鼠30只随机分为空白对照组、骨癌痛组和Ifenprodil组,每组10只。骨癌痛组和Ifenprodil组大鼠右胫骨骨髓腔接种MADB-106细胞3μL(4.8×109/mL),而空白对照组给予同等剂量的生理盐水作对照。术后第14天Ifenprodil组rACC内给予NR2B受体阻断剂Ifenprodil 1.2μL,而空白对照组和骨癌痛组给予同等剂量的生理盐水。分别于术前1天,以及术后第3、7、10、12及14天采用Von Frey刺激法测量大鼠右后爪机械刺激痛阈的变化。术后第14天rACC内给予Ifenprodil后观测骨癌痛大鼠伴随的痛厌恶情绪体验。结果骨癌痛组及Ifenprodil组大鼠自术后第10天至第14天右后爪机械刺激痛阈值明显降低(P<0.05),而空白对照组无改变(P>0.05)。组间比较术后第10、12和14天骨癌痛组和Ifenprodil组明显低于空白对照组(P<0.05)。条件性位置回避实验显示,骨癌痛组大鼠A室滞留时间的百分比为(30±4)%,低于空白对照组(52±5)%(P<0.05);经rACC内注射Ifenprodil后A室滞留时间的百分比为(42±5)%,较骨癌痛组升高但仍低于空白对照组(P<0.05)。结论前扣带回皮层注射NR2B受体阻断剂ifenprodil能够减轻骨癌痛大鼠伴随的痛厌恶情绪体验。

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.