Martami Fahimeh, Holton Kathleen F
Departments of Health Studies, American University, 4400 Massachusetts Ave NW, Washington, DC, 20016, USA.
Department of Neuroscience, American University, Washington, DC, USA.
J Headache Pain. 2025 May 6;26(1):101. doi: 10.1186/s10194-025-02043-x.
The exact mechanisms that trigger the activation of the trigeminovascular system in migraine remain unclear. The involvement of calcitonin gene-related peptide (CGRP) in migraine is well-documented, and treatments aimed at blocking CGRP activity have proven successful in reducing migraine attacks for some patients. However, around one third of individuals do not respond to these therapies, which are also limited by factors like cost, side effects, and contraindications. There is growing evidence suggesting that glutamate, an excitatory neurotransmitter, plays a crucial role in the onset and maintenance of migraine pain, partially by enhancing CGRP release. Increased glutamate levels have been linked to both peripheral and central sensitization, potentially contributing to the development and persistence of chronic migraine. The relationship between CGRP and glutamate is complex, with glutamate possibly acting as an upstream trigger for CGRP release. This review examines the interplay between CGRP and glutamate, and their involvement in both peripheral and central sensitization. It also explores the therapeutic potential of targeting either glutamate or CGRP, aiming to address both peripheral and central migraine mechanisms. Finally, the role of triggers in migraine initiation at the peripheral level is discussed, offering insights into potential preventive strategies.
偏头痛中触发三叉神经血管系统激活的确切机制仍不清楚。降钙素基因相关肽（CGRP）参与偏头痛已有充分记录，针对阻断CGRP活性的治疗已被证明对一些患者减少偏头痛发作是成功的。然而，约三分之一的个体对这些疗法无反应，这些疗法还受到成本、副作用和禁忌症等因素的限制。越来越多的证据表明，谷氨酸作为一种兴奋性神经递质，在偏头痛疼痛的发作和维持中起关键作用，部分原因是通过增强CGRP的释放。谷氨酸水平升高与外周和中枢敏化均有关联，可能促成慢性偏头痛的发展和持续。CGRP与谷氨酸之间的关系很复杂，谷氨酸可能作为CGRP释放的上游触发因素。本综述探讨了CGRP与谷氨酸之间的相互作用，以及它们在外周和中枢敏化中的作用。它还探讨了针对谷氨酸或CGRP的治疗潜力，旨在解决外周和中枢偏头痛机制。最后，讨论了触发因素在偏头痛外周水平起始中的作用，为潜在的预防策略提供见解。
