【作者】 杨娟；

【导师】 冯智英；

【作者基本信息】 浙江大学 ， 临床医学（专业学位）， 2017， 硕士

【摘要】 目的:本实验通过疼痛行为学检测以评估小鼠皮肤/肌肉切口牵拉模型(skin/muscleincision and retraction,SMIR)是否造模成功,探讨该模型作为术后慢性疼痛(chronic postsurgical pain,CPSP)模型的可行性及稳定性,为CPSP的发生机制及治疗提供稳定的研究基础;同时应用多种不同作用机制的镇痛药物干预小鼠SMIR模型以观察疗效并评估该模型的行为学特征。方法:(1)将实验鼠随机分为皮肤/肌肉切口牵拉组(SMIR组)和皮肤/肌肉切口不牵拉组(Sham组),在术前Id、术后1d、3d、7d、10d、14d、18d检测其机械缩足反射阈值及热缩足反射阈值,验证该模型的稳定性。(2)观察可乐定、右美托咪定和加巴喷丁对SMIR小鼠疼痛行为学的影响:于术后第3天腹腔注射可乐定(0.02mg/kg、0.1mg/kg、0.5mg/kg)、右美托咪定(0.4ug/kg、2ug/kg、10ug/kg)及加巴喷丁(10mg/kg、20mg/kg、50mg/kg),观察其对SMIR小鼠机械缩足反射影响;分别检测可乐定、加巴喷丁和右美托咪定对SMIR小鼠条件性位置偏爱的影响:于术后第4天腹腔注射0.5mg/kg可乐定、10ug/kg右美托咪定和50mg/kg加巴喷丁,观察是否会诱发SMIR小鼠条件性位置偏爱。结果:(1)跟假手术组及术前基础值相比,SMIR组造模前后机械痛阈值从术后第一天开始明显下降,有统计学差异(P<0.001),术后第10天至第14天开始恢复,但仍有统计学差异(P<0.05),直至术后第18天恢复正常;热痛阈值无统计学差异(P>0.05)。(2)跟生理盐水组相比,可乐定、右美托咪定和加巴喷丁能提高SMIR小鼠机械痛阈值,有统计学差异(P<0.05),且呈剂量依赖性。0.5mg/kg可乐定和10ug/kg右美托咪定均能诱发SMIR小鼠的条件性位置偏爱(P<0.05),而50mg/kg加巴喷丁无法诱发SMIR小鼠的条件性位置偏爱(P>0.05)。结论:小鼠皮肤/肌肉切口牵拉建立术后慢性疼痛模型成功率高、简单易行且具有一定的稳定性。可乐定、右美托咪定及加巴喷丁能够提高SMIR小鼠机械痛阈值,且呈剂量依赖性。此外,0.5mg/kg可乐定和10ug/kg右美托咪定可以改善其自发痛,50mg/kg加巴喷丁不能改善其自发痛。更多还原

【Abstract】 Obejective:To verify the stability of skin/muscle incision and retraction model in mouse by ethology and to investigate the feasibility of establishing an animal model of chronic postsurgical pain in mouse.Furthermore,we assess effect of kinds of analgesics on this model and its characteristics.Methods:(1)Mouse were randomly assigned to 2 groups:skin/muscle incision and retraction(SMIR)group and skin/muscle incision without retraction(Sham)group,Paw withdrawal thresholds to mechanical stimuli and heat stimuli were recorded at dayl before surgery,day 1,day 3,day 7,day 10,day 14 and 18 after surgery.(2)Evaluating the analgesic effects of clonidine,dexmedetomidine and gabapentin on SMIR in mice:systemic injection clonidine(0.02mg/kg、0.1mg/kg、0.5mg/kg),dexmedetomidine(0.4ug/kg、2ug/kg、lOug/kg)and gabapentin(10mg/kg、20mg/kg、50mg/kg)on day 3 after surgery,assessing the effect on mechanical withdrawal thresholds.Evaluating the effects of clonidine,dexmedetomidine and gabapentin on the spontaneous pain by using a conditional place preference(CPP)behavioral paradigm:systemic injection clonidine(0.5mg/kg),dexmedetomidine(lOug/kg)and gabapentin(50mg/kg)on day 4 after surgery,observing whether they can arise CPP.Results:(1)SMIR-evoked mechanical hypersensitivity was observed by postoperative dayl(P<0.001),most prominent between postoperative days 1-10(P<0.001),persisted until at least postoperative day 14(P<0.05)and had dissipated by postoperative day 18.SMIR did not evoke significant heat hyperalgesia(P>0.05).(2)Systemic injection of clonidine,dexmedetomidine and gabapentin raised the PWTs in SMIR mice,and these effects were dose dependent.Systemic injection of 0.5mg/kg clonidine,lOug/kg dexmedetomidine alleviated spontaneous pain by chronic surgery pain in the CPP test,but 50mg/kg gabapentin did not alleviated spontaneous pain,there was no significant difference in preference changes to conditioning-box.ConclusionThese data suggests that skin/muscle incision and retraction model in mice evokes a persistent pain syndrome.Clonidine,dexmedetomidine and gabapentin can relieve mechanical hyperalgesia on dose-dependent.furthermore,0.5mg/kg clonidine and lOug/kg dexmedetomidine can alleviate spontaneous pain of SMIR,but 50mg/kg gabapentin cannot alleviate spontaneous pain of SMIR.更多还原