Spontaneous trigeminal allodynia in rats: a model of primary headache.
Spontaneous trigeminal allodynia in rats: a model of primary headache.
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DOI：
10.1111/j.1526-4610.2012.02247.x
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发表时间：
2012-10
期刊：
影响因子：
5
通讯作者：
Silberstein SD
中科院分区：
文献类型：
--
作者：
Oshinsky ML;Sanghvi MM;Maxwell CR;Gonzalez D;Spangenberg RJ;Cooper M;Silberstein SD
动物模型对于研究头痛疾病的病理生理学和作为新疗法的筛选工具是必不可少的。大多数动物模型修改了正常动物，试图模仿偏头痛症状。它们需要操纵以激活三叉神经或硬脑膜伤害感受器。充其量，它们是继发性头痛的模型。没有现有的模型可以解决这个基本问题：原发性头痛是如何自发发生的？在野生型Sprague-Dawley大鼠获得基线眶周von Frey阈值的过程中，我们发现了一只自发性发作性三叉神经异常性疼痛（表现为眶周疼痛阈值的发作性变化）的大鼠。随后的交配表明，这种特征是遗传的。自发性三叉神经异常性疼痛的动物使我们能够研究原发性复发性头痛疾病的病理生理学。为了验证这是一个偏头痛模型，我们测试了临床证明的急性和预防性偏头痛治疗对大鼠眶周敏感性自发变化的影响。舒马曲坦、酮咯酸和双氢麦角胺暂时逆转了低眶周痛阈。丙戊酸长期治疗30天可预防三叉神经异常性疼痛的自发变化。停药后，大鼠恢复到其自发性发作性阈值变化的基线。我们还测试了已知的化学物质对人类偏头痛的影响。在大鼠没有异常性疼痛并显示正常眶周von Frey阈值的日子，三硝酸甘油和降钙素基因相关肽诱导眶周疼痛阈值显著降低。该模型可用作药物开发的预测模型和用于头痛诊断和治疗的假定生物标志物的研究。
Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.
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影响因子：
8.6
作者：
Brefel-Courbon, C;Payoux, P;Rascol, O
通讯作者：
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