帕金森病模型大鼠的痛觉敏化及其时反应量-效关系
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摘要
目的:观察帕金森病(PD)模型大鼠的痛觉敏感性并分析其痛觉时反应量-效关系(TDRR)。方法:取55只雄性SD大鼠随机分为正常组(n=13)、假手术组(n=8)、模型组(n=34),应用6-羟多巴胺右侧纹状体注射法制备模型,假手术组注射等容量生理盐水,造模后4周腹腔注射阿朴吗啡,检测其异常旋转行为进行模型鉴定。其后,使用Von Fery纤维丝测痛仪检测各组大鼠的机械刺激缩足反应阈值(PWMT),用光辐射热测痛仪检测不同光强度下的热辐射甩尾反射潜伏期(TFL)并分析其TDRR。结果:①模型组术后4周的模型鉴定显示旋转≥7 r/min造模成功的27只;②模型组(n=27)较另两组大鼠的PWMT降低(P<0.01),且假手术组(n=6)与正常组大鼠相似(P>0.05);③在光照强度为34、51、76时模型组大鼠的TFL较另两组均缩短(P<0.01),而另两组间均相似;④重复测量的双因素方差分析显示,光强度、光强度×组间(P<0.05)及组间(P<0.01)的变异均有统计学意义,两两比较模型组较另两组甩尾反应潜伏期缩短(P<0.01);⑤对3组大鼠的光强度-TFL关系数据,分别用双曲线型TDRR模型Y=c~(s+1)/(x-a)~s+b进行曲线拟合,结果模型组为c=41.29,s=7.303,a=-17.47,b=1.261(最短潜伏期,s),R~2=0.8971,主要显示参数a较另两组减小的变化。结论:帕金森病模型大鼠存在痛觉敏化和痛觉TDRR曲线左移的特征。
Objective:To observe the pain sensitization and timed dose-response relationship(TDRR) in model rats of Parkinson disease(PD).Methods:Fifty-five male SD rats were randomized into normal(n=13),sham operation(n=8) and model(n=34) groups.Rat models were developed using 6-hydroxydopamine(6-OHDA) injection into the right sided striatum,and equivalent volume of normal saline was administered in rats in the sham operation group.After 4 weeks,apomorphine was injected(i.p.) to identify PD model rats by observing the abnormal rotational behavior.Von Frey filament was used to measure the paw withdrawal mechanical threshold(PWMT) and the tail-flick latency(TFL) upon thermal radiation under diverse light intensity,for which the TDRR of TFL was analyzed in all rats.Results:①Twenty-seven rats showed steadily apomorphine-induced rotation over 7 r/min;②PWMT of model group rats(n=27) was decreased than that of 2 other groups(P<0.01),while that in normal group and sham operation group(n=6) rats was similar(P>0.05);③TFLs at focus intensity of 34,51 and 76 were obviously reduced in model rats compared to 2 other groups(P<0.01),and TFLs remained similar in 2 other groups of rats;④Two-way repeated measures ANOVA showed significant difference in the variations among light intensities,and intensity between groups.By pair-wise comparison,the difference of rat TFL between model group and 2 other groups was significant either(P<0.01);⑤ Hyperbolic TDRR model Y=c~(s+1)/(x-a)~s+b was used for curve fitting to analyze the data of light intensity-TFL relationship in all groups.The results indicated c=41.29,s=7.303,a=-17.47,b=1.261 and R~2=0.8971 in model group,and decreased parameter a in comparison with that of 2 other groups.Conclusion:The observation demonstrates that hyperalgesia does exist,and the pain TDRR curve tends to be left shifted in PD model rats.
Objective:To observe the pain sensitization and timed dose-response relationship(TDRR) in model rats of Parkinson disease(PD).Methods:Fifty-five male SD rats were randomized into normal(n=13),sham operation(n=8) and model(n=34) groups.Rat models were developed using 6-hydroxydopamine(6-OHDA) injection into the right sided striatum,and equivalent volume of normal saline was administered in rats in the sham operation group.After 4 weeks,apomorphine was injected(i.p.) to identify PD model rats by observing the abnormal rotational behavior.Von Frey filament was used to measure the paw withdrawal mechanical threshold(PWMT) and the tail-flick latency(TFL) upon thermal radiation under diverse light intensity,for which the TDRR of TFL was analyzed in all rats.Results:①Twenty-seven rats showed steadily apomorphine-induced rotation over 7 r/min;②PWMT of model group rats(n=27) was decreased than that of 2 other groups(P<0.01),while that in normal group and sham operation group(n=6) rats was similar(P>0.05);③TFLs at focus intensity of 34,51 and 76 were obviously reduced in model rats compared to 2 other groups(P<0.01),and TFLs remained similar in 2 other groups of rats;④Two-way repeated measures ANOVA showed significant difference in the variations among light intensities,and intensity between groups.By pair-wise comparison,the difference of rat TFL between model group and 2 other groups was significant either(P<0.01);⑤ Hyperbolic TDRR model Y=c~(s+1)/(x-a)~s+b was used for curve fitting to analyze the data of light intensity-TFL relationship in all groups.The results indicated c=41.29,s=7.303,a=-17.47,b=1.261 and R~2=0.8971 in model group,and decreased parameter a in comparison with that of 2 other groups.Conclusion:The observation demonstrates that hyperalgesia does exist,and the pain TDRR curve tends to be left shifted in PD model rats.
引文
[1] KHANDHAR SM,MARKS WJ.Epidemiology of Parkinson′s disease[J].Dm-Dis Mon,2007,53(4):200-205.
[2] COOKSON MR.The biochemistry of Parkinson′s disease[J].Annu Rev Biochem,2005,74(1):29-52.
[3] 王姝,莫英绪,王大成.帕金森病发病因素的研究现状[J].医学信息,2018,31(1):46-48.
[4] 杨瑞鑫,陈立刚.滋肾益髓方治疗帕金森病运动及非运动症状的疗效观察[J].现代医学与健康研究电子杂志,2018,2(17):181-182.
[5] 张志丽.探讨帕金森病患者非运动症状的临床特征[J].世界最新医学信息文摘,2018,18(78):21-22,42.
[6] 江名芳,于生元.帕金森病的疼痛[J].中国疼痛医学杂志,2013,19(12):743-746.
[7] 何延洁,刘晓加,邹海强.帕金森病疼痛的研究进展[J].实用老年医学,2015,29(12):976-978.
[8] 李巳艽,毛成洁,陈怡,等.伴发疼痛的帕金森病患者正中神经感觉阈值及疼痛耐受阈值的变化[J].中华神经科杂志,2015,48(5):395-399.
[9] 杨坤,张书婷,郭媛,等.反复力竭游泳对大鼠痛阈的影响[J].中国药物依赖性杂志,2011,20(4):262-264.
[10] 李冬辉,宋祥胜,黄华云,等.帕金森病相关性疼痛的影响因素分析[J].现代实用医学,2018,30(8):997-998,976.
[11] WANG MENGYA,SUN RUIYUAN.Mathematical models for hyperbolic type of timed dose-response relationship of drugs[J].Acta Pharmacol Sin,1987,8(6):481-486.
[12] 汪萌芽,孙瑞元.时反应量效关系及其研究现状[J].中国药理学通报,1987,3(2):111-114.
[13] 汪萌芽,孙瑞元.时反应量效关系数学模型的探讨[J].科技通报,1986,2(4):33-34.
[14] 胡凤玉,蒋娟,汪萌芽.迷宫学习模型实验的时反应量-效关系[J].皖南医学院学报,2001,20(3):159-161.
[15] 秦雯,曲睿,汪萌芽.大鼠空间学习记忆能力测试的时反应量-效关系[J].皖南医学院学报,2010,29(6):462-465.
[16] 余雪霏,郑超,汪萌芽,等.大鼠光辐射热甩尾试验的时反应量-效关系[J].皖南医学院学报,2014,33(2):176-180.
[17] 王晓晓,付文玉,庄文欣,等.改良纹状体内两点注射6-OHDA法制备大鼠帕金森病模型[J].神经解剖学杂志,2015,31(2):187-192.
[18] PAXINOS G,WATSO C.The rat brain in stereotaxic coordinates[M].Academic Press Sydney,1985,25:87-92.
[19] 眭明红,李晶晶,向云,等.电针对炎性痛大鼠镇痛作用的观察[J].康复学报,2018,28(3):32-36,41.
[20] KLINGELHOEFER L,REICHMANN H.Pathogenesis of Parkinson disease-the gut-brain axis and environmental factors[J].Nat Rev Neurol,2015,11(11):625-636.
[21] YUN JW,AHN JB,KANG BC.Modeling Parkinson′s disease in the common marmoset(Callithrix jacchus):overview of models,methods,and animal care[J].Lab Anim Res,2015,31(4):155-I65.
[22] 李进,孙杰,赵楠,等.3 种不同脑区定点注射 6-OHDA 单侧损伤大鼠帕金森病模型的比较研究[J].河北医科大学学报,2016,37(6):667-671.
[2] COOKSON MR.The biochemistry of Parkinson′s disease[J].Annu Rev Biochem,2005,74(1):29-52.
[3] 王姝,莫英绪,王大成.帕金森病发病因素的研究现状[J].医学信息,2018,31(1):46-48.
[4] 杨瑞鑫,陈立刚.滋肾益髓方治疗帕金森病运动及非运动症状的疗效观察[J].现代医学与健康研究电子杂志,2018,2(17):181-182.
[5] 张志丽.探讨帕金森病患者非运动症状的临床特征[J].世界最新医学信息文摘,2018,18(78):21-22,42.
[6] 江名芳,于生元.帕金森病的疼痛[J].中国疼痛医学杂志,2013,19(12):743-746.
[7] 何延洁,刘晓加,邹海强.帕金森病疼痛的研究进展[J].实用老年医学,2015,29(12):976-978.
[8] 李巳艽,毛成洁,陈怡,等.伴发疼痛的帕金森病患者正中神经感觉阈值及疼痛耐受阈值的变化[J].中华神经科杂志,2015,48(5):395-399.
[9] 杨坤,张书婷,郭媛,等.反复力竭游泳对大鼠痛阈的影响[J].中国药物依赖性杂志,2011,20(4):262-264.
[10] 李冬辉,宋祥胜,黄华云,等.帕金森病相关性疼痛的影响因素分析[J].现代实用医学,2018,30(8):997-998,976.
[11] WANG MENGYA,SUN RUIYUAN.Mathematical models for hyperbolic type of timed dose-response relationship of drugs[J].Acta Pharmacol Sin,1987,8(6):481-486.
[12] 汪萌芽,孙瑞元.时反应量效关系及其研究现状[J].中国药理学通报,1987,3(2):111-114.
[13] 汪萌芽,孙瑞元.时反应量效关系数学模型的探讨[J].科技通报,1986,2(4):33-34.
[14] 胡凤玉,蒋娟,汪萌芽.迷宫学习模型实验的时反应量-效关系[J].皖南医学院学报,2001,20(3):159-161.
[15] 秦雯,曲睿,汪萌芽.大鼠空间学习记忆能力测试的时反应量-效关系[J].皖南医学院学报,2010,29(6):462-465.
[16] 余雪霏,郑超,汪萌芽,等.大鼠光辐射热甩尾试验的时反应量-效关系[J].皖南医学院学报,2014,33(2):176-180.
[17] 王晓晓,付文玉,庄文欣,等.改良纹状体内两点注射6-OHDA法制备大鼠帕金森病模型[J].神经解剖学杂志,2015,31(2):187-192.
[18] PAXINOS G,WATSO C.The rat brain in stereotaxic coordinates[M].Academic Press Sydney,1985,25:87-92.
[19] 眭明红,李晶晶,向云,等.电针对炎性痛大鼠镇痛作用的观察[J].康复学报,2018,28(3):32-36,41.
[20] KLINGELHOEFER L,REICHMANN H.Pathogenesis of Parkinson disease-the gut-brain axis and environmental factors[J].Nat Rev Neurol,2015,11(11):625-636.
[21] YUN JW,AHN JB,KANG BC.Modeling Parkinson′s disease in the common marmoset(Callithrix jacchus):overview of models,methods,and animal care[J].Lab Anim Res,2015,31(4):155-I65.
[22] 李进,孙杰,赵楠,等.3 种不同脑区定点注射 6-OHDA 单侧损伤大鼠帕金森病模型的比较研究[J].河北医科大学学报,2016,37(6):667-671.
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