Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment.
Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment.
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DOI：
10.3390/ijms232213807
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发表时间：
2022-11-09
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
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偏头痛的临床特征是反复头痛发作，导致相当大的残疾。许多偏头痛患者会出现后综合征，其症状包括疲劳和恐惧症。降钙素基因相关肽（GGRP）在偏头痛发病机制中起着重要作用。皮质扩散性去极化（CSD），偏头痛先兆的生物学相关，敏感三叉神经血管系统。在我们以前的研究中，CSD在72 h时引起光区运动功能减退和恐惧症倾向，此时三叉神经敏化已消失。我们建议，这种CSD诱导的疾病状态将有助于探索偏头痛后综合征的治疗策略。在本研究中，我们观察到CGRP受体拮抗剂olcegepant在CSD诱导后72 h防止了光区的运动不足，并改善了光耐受性。此外，olcegepant治疗显著提高了CSD后72小时的面部热痛阈值。我们的研究结果提出了这样一种可能性，即CGRP阻断可能通过增强偏头痛后期的光耐受性而有效改善光环境中的活动减退。此外，我们的数据表明，CGRP通路可能会降低面部热痛阈值，即使在没有明显的三叉神经敏化，这提供了一个重要的线索，从而CGRP阻断偏头痛预防的潜在机制。
A migraine is clinically characterized by repeated headache attacks that entail considerable disability. Many patients with migraines experience postdrome, the symptoms of which include tiredness and photophobia. Calcitonin gene-related peptide (GGRP) is critically implicated in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, sensitizes the trigeminovascular system. In our previous study, CSD caused hypomotility in the light zone and tendency for photophobia at 72 h, at which time trigeminal sensitization had disappeared. We proposed that this CSD-induced disease state would be useful for exploring therapeutic strategies for migraine postdrome. In the present study, we observed that the CGRP receptor antagonist, olcegepant, prevented the hypomotility in the light zone and ameliorated light tolerability at 72 h after CSD induction. Moreover, olcegepant treatment significantly elevated the threshold for facial heat pain at 72 h after CSD. Our results raise the possibility that CGRP blockade may be efficacious in improving hypoactivity in the light environment by enhancing light tolerability during migraine postdrome. Moreover, our data suggest that the CGRP pathway may lower the facial heat pain threshold even in the absence of overt trigeminal sensitization, which provides an important clue to the potential mechanism whereby CGRP blockade confers migraine prophylaxis.
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DOI：
10.1177/0333102417712719
发表时间：
2018-04
期刊：
Cephalalgia : an international journal of headache
影响因子：
--
作者：
Kayama Y;Shibata M;Takizawa T;Ibata K;Shimizu T;Ebine T;Toriumi H;Yuzaki M;Suzuki N
通讯作者：
Suzuki N
DOI：
10.1186/s10194-022-01467-z
发表时间：
2022-08-08
期刊：
The journal of headache and pain
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.4
作者：
Lampl, Christian;Thomas, Hallie;Steiner, Timothy J.
通讯作者：
Steiner, Timothy J.
影响因子：
4.9
作者：
Ayata, Cenk
通讯作者：
Ayata, Cenk
影响因子：
3.3
作者：
Cornelison LE;Hawkins JL;Durham PL
通讯作者：
Durham PL