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摘要：
目的 观察新型抗抑郁药帕罗西汀（Paroxetine）对慢性缩窄性损伤（Chronic constriction injury,CCI）疼痛模型小鼠痛阈的影响，及与海马CA1区脑源性神经营养因子（Brain-derived neurotrophic factor,BDNF）表达的关系。 方法 雄性健康小鼠48只，采用随机数字表法随机分为假手术组（Sham组）和慢性缩窄性损伤模型组（CCI组），两组小鼠于术后第3天开始分别给予Paroxetine(20mg)或等量生理盐水（NS）灌胃，连续给药7天后，从第8天开始停止给药，再分为Sham+P组、Sham+NS组、CCI+P组、CCI+NS组，每组12只。①于CCI模型建立后第0、3天，以及给药后第1、3、7、8、9、10、11天分别检测实验小鼠的热缩足潜伏期(paw withdrawal latency,PWL)变化。②将CCI+P组、CCI+NS组实验动物按随机数字表法随机分成CCI+P+BDNF组、CCI+P+PBS组、CCI+NS+BDNF组、CCI+NS+PBS组每组6只，在Paroxetine 给药7天后行脑立体定位，于CCI对侧海马CA1区注射小剂量外源性BDNF（）。观察BDNF注射后的1、2、4 h的疼痛行为学变化。 结果 与Sham+NS比较，Sham+P组灌胃后各时间点PWL差异无统计学意义（p>0.05）;与CCI+NS组比较，CCI+P在灌胃后第3 d PWL(6.66±1.43)明显升高（p<0.01)，在灌胃后第7d PWL(8.36±1.13)升高更明显（p<0.001）,CCI+P组在停药第1 d PWL(7.84±0.37)仍较高（p<0.05），然而，CCI+P组从停药第2d开始差异无统计学意义（p>0.05）;与CCI+NS+PBS组比较，CCI+NS+BDNF组在各时间点PWL差异无统计学意义（P>0.05）,与CCI+P+PBS组比较，CCI+P+BDNF组PWL在注药1 h (5.78±0.39)、2 h（ 5.34±0.47）明显降低（ p<0.001）,并且可以至少持续至注药4h,CCI+P+BDNF组在注药4h PWL(5.85±1.13)差异有意义（p<0.05）。 结论 新型抗抑郁药Paroxetine有确切的镇痛效果，其机制是通过抑制海马内BDNF的升高而产生镇痛作用。
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Abstract: [Abstract] Objective To investigate the effect of the new Antidepressant drug Paroxetine on the pain threshold in mice underwent neuropathic pain induced by CCI and the relation between the analgestic effect of Paroxetine with expression of BDNF in hippocampal CA1 region . Methods Healthy male mice of 48, according to the random number table method were randomly divided into two groups:sham operated control and CCI group.Two groups of mice from started on the 3 postoperative day were orally given Paroxetine and saline,continuous administration for 7 days,starting from the eighth day withdrawal,were divided into group Sham+P,group Sham+NS, group CCI+P and group CCI+NS,12 rats in each group.① Pwl was measured in 0 day, 3 day after the operation and 1、 3、 7、8、9、10、11 days after administration respectively.② The group CCI+P and group CCI+NS of experimental animal were randomly divided into group CCI +P+BDNF, group CCI+P+PBS ,group CCI+NS+BDNF and group CCI+NS+PBS,6 rats in each group.After 7 days of treatment of Paroxetine,Cerebral Stereotactic was conducted.Small dose of exogenous BDNF was injected in the CCI contralateral hippocampus CA1 region. Results Compared with group Sham+NS,the PWL of group Sham+P at each time point after intragastric administration had no statistically significant difference（ p>0.05 );Compared with group CCI+NS,the PWL increased significantly in 3、7 days of group CCI+P[(6.66±0.35) ,(8.36±0.33)]after intragastric administration and the difference was statistically significant(p<0.001), the PWL of group CCI +P(7.84±0.37) had statistically significant difference in 1 day after discontinuation (p<0.05);The PWL difference between group CCI+P and group CCI+NS decreased gradually after discontinuation and the difference was not statistically significant 2 days after discontinuation(p>0.05).Compared with group CCI+NS+PBS,the PWL of group CCI+NS+BDNF at each time point had no statistically significant difference（p>0.05).
Compared with group CCI+P+PBS,the PWL of 1、2 h of group CCI+P+BDNF[(5.78±0.39)、（5.34±0.47）]decreased significantly(p<0.001), and it can last until 4 h after injection at last, the PWL of 4 h of group CCI +P+BDNF (5.85±1.13)had statistically significant difference (p<0.05). Conclusions Paroxetine , a kind of new antidepressant drug , has precise analgesic effect on neuropathic pain and its analgestic effect has a close relation with the decrease of expression of brain-derived neurotrophic factor( BDNF )in hippocampal CA1 region.
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