Melo-Carrillo Agustin
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, CLS-624-E, 3 Blackfan Circle, Boston, MA, 02215, USA.
Harvard Medical School, Boston, MA, USA.
J Headache Pain. 2025 Apr 28;26(1):91. doi: 10.1186/s10194-025-02012-4.
Cortical spreading depression (CSD) is a wave of neuronal and glial depolarization followed by suppressed neural activity, thought to underlie migraine aura. While Calcitonin Gene-Related Peptide (CGRP) is well established in migraine pathophysiology, its role in CSD remains uncertain. This comment evaluates evidence suggesting that CGRP is not directly involved in CSD initiation or propagation but may contribute to nociceptive activation associated with migraine. While some studies report CGRP-related effects on CSD susceptibility, methodological limitations raise concerns about their interpretation. Electrophysiological data indicate that CGRP does not influence the ionic mechanisms driving CSD. However, CGRP plays a key role in sensitizing nociceptive neurons, and CGRP-targeting drugs effectively modulate migraine pain without altering CSD dynamics. Clinical findings further suggest that peripheral CGRP inhibition reduces headache burden, potentially allowing the brain to recover from chronic pain states. In conclusion, while CGRP is integral to migraine pain modulation, its direct involvement in CSD appears minimal, highlighting distinct pathways for aura and headache pathophysiology.
皮层扩散性抑制（CSD）是一种神经元和胶质细胞去极化波，随后是神经活动抑制，被认为是偏头痛先兆的基础。虽然降钙素基因相关肽（CGRP）在偏头痛病理生理学中已得到充分证实，但其在CSD中的作用仍不确定。本评论评估了相关证据，这些证据表明CGRP并不直接参与CSD的起始或传播，但可能促成与偏头痛相关的伤害性激活。虽然一些研究报告了CGRP对CSD易感性的相关影响，但方法学上的局限性引发了对这些结果解读的担忧。电生理数据表明，CGRP不影响驱动CSD的离子机制。然而，CGRP在使伤害性神经元敏感化方面起关键作用，且靶向CGRP的药物可有效调节偏头痛疼痛而不改变CSD动态。临床研究结果进一步表明，外周CGRP抑制可减轻头痛负担，这可能使大脑从慢性疼痛状态中恢复。总之，虽然CGRP对于偏头痛疼痛调节不可或缺，但其直接参与CSD的程度似乎很小，这凸显了先兆和头痛病理生理学的不同途径。
