Characterization of a mouse model of headache.
Characterization of a mouse model of headache.
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DOI：
10.1097/j.pain.0000000000000578
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发表时间：
2016-08
期刊：
影响因子：
7.4
通讯作者：
Cao YQ
中科院分区：
文献类型：
--
作者：
Huang D;Ren L;Qiu CS;Liu P;Peterson J;Yanagawa Y;Cao YQ
偏头痛和其他原发性头痛疾病影响大量人群，并导致使人衰弱的疼痛。建立显示长期和持续头痛（偏头痛最常见和致残的症状）行为相关性的动物模型，对于阐明疾病机制以及确定药物靶点至关重要。我们已经开发了一种头痛的小鼠模型，使用辣椒素沿着与炎性介质的混合物（IScap）的硬脑膜应用来模拟头痛发作的诱导。这引起了间歇性的头部定向擦拭和抓挠以及三叉神经节神经元中c-Jun N-末端激酶的磷酸化。有趣的是，硬脑膜应用IScap优先诱导FOS蛋白表达的兴奋性，但不是抑制性颈/髓背角神经元。IScap诱导的行为的持续时间和福斯阳性神经元的数量在个别小鼠中呈正相关;通过抗偏头痛药物舒马曲坦的预处理，两者都降低到对照水平。硬膜内应用降钙素基因相关肽（CGRP）受体拮抗剂CGRP（8-37）也能有效阻断IScap诱导的行为，提示硬膜内内源性CGRP的释放是IScap诱导的伤害性感受所必需的。这些数据表明，硬脑膜IScap诱导的小鼠疼痛反应行为可能与人类持续头痛有关。此外，硬脑膜应用IScap增加了雌性小鼠的休息时间。总之，我们在这里提出了第一个详细的研究，使用硬脑膜应用IScap在小鼠。该模型可应用于转基因小鼠，为偏头痛发病机制和治疗靶点的研究奠定基础。
Migraine and other primary headache disorders affect a large population and cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting and ongoing headache, the most common and disabling symptom of migraine, is vital for the elucidation of disease mechanisms as well as the identification of drug targets. We have developed a mouse model of headache, using dural application of capsaicin along with a mixture of inflammatory mediators (IScap) to simulate the induction of a headache episode. This elicited intermittent head-directed wiping and scratching as well as the phosphorylation of c-Jun N-terminal kinase in trigeminal ganglion neurons. Interestingly, dural application of IScap preferentially induced FOS protein expression in the excitatory but not inhibitory cervical/medullary dorsal horn neurons. The duration of IScap-induced behavior and the number of FOS-positive neurons correlated positively in individual mice; both were reduced to the control level by the pretreatment of anti-migraine drug sumatriptan. Dural application of CGRP(8–37), the calcitonin gene-related peptide (CGRP) receptor antagonist, also effectively blocked IScap-induced behavior, suggesting that the release of endogenous CGRP in dura is necessary for IScap-induced nociception. These data suggest that dural IScap-induced nocifensive behavior in mice may be mechanistically related to the ongoing headache in humans. In addition, dural application of IScap increased resting time in female mice.. Taken together, we present here the first detailed study using dural application of IScap in mice. This headache model can be applied to genetically modified mice to facilitate the research for the mechanisms and therapeutic targets for migraine headache.