大鼠反复给予硝酸甘油的效应；偏头痛相关终点及慢性化建模
The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification.
作者信息
Harris Hannah M, Carpenter Jessica M, Black Jonathan R, Smitherman Todd A, Sufka Kenneth J
机构信息
Department of Psychology, University of Mississippi, 207 Peabody Building, University, MS 38677, USA.
Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA.
出版信息
J Neurosci Methods. 2017 Jun 1;284:63-70. doi: 10.1016/j.jneumeth.2017.04.010. Epub 2017 Apr 23.
BACKGROUND
Rodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance.
NEW METHOD
Rats received 5 nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15days. Behavioral endpoints were assessed 110min post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia.
RESULTS
Animals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode.
COMPARISON WITH EXISTING METHODS
Most NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia.
CONCLUSIONS
This repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints.
背景
啮齿动物模型通常采用单次注射硝酸甘油来诱发偏头痛，但临床人群中的偏头痛表现为反复发作。此外，这些模型所量化的行为终点与发作性偏头痛或偏头痛慢性化的临床特征不一致，因此可能会限制其转化相关性。
新方法
大鼠每隔一天接受5次硝酸甘油（10mg/kg/2ml）、丙二醇/乙醇赋形剂或生理盐水注射，持续15天。在注射硝酸甘油后110分钟评估行为终点，包括在明/暗箱中因畏光而花费的时间以及活动、面部疼痛表情和触觉性痛觉过敏。
结果
给予硝酸甘油的动物表现出畏光、活动减少和面部疼痛表情增加。在接受赋形剂治疗的动物中也观察到了类似的畏光和活动变化，但这些变化在第4次或第5次注射后趋于减弱。在第5次发作时，硝酸甘油组出现了自发性触觉性痛觉过敏。
与现有方法的比较
大多数硝酸甘油偏头痛模型采用单次给予硝酸甘油并量化诱发的痛觉过敏。该范式采用反复给予硝酸甘油的发作以及畏光、活动减退和面部 grimace 终点的临床相关测量，并引入了一种新颖的实验装置来量化自发性痛觉过敏。
结论
这种重复给予硝酸甘油的程序和终点测量分别与发作性偏头痛的频率和临床表现及其慢性化相一致。此外，丙二醇乙醇赋形剂对偏头痛终点有影响。
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