Kalatharan Veberka, Al-Karagholi Mohammad Al-Mahdi
Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansens Vej 5, DK-2600 Glostrup, Denmark.
J Clin Med. 2023 Mar 10;12(6):2156. doi: 10.3390/jcm12062156.
: Several acute and preventive medications were developed for the treatment of migraine. Yet, a significant proportion of patients reports an inadequate response and a lack of tolerability, emphasizing the need for new options. Glutamate is the most important excitatory neurotransmitter in the brain, and glutamate receptors including N-Methyl-D-Aspartate Receptor (NMDAR) are expressed at several levels of the trigeminovascular system, which is the anatomical and physiological substrate of migraine pain. To review preclinical and clinical studies investigating the role of the NMDAR in migraine pathophysiology. No protocol was registered for this study. References for the present review were identified from a narrative search of the PubMed database. Search terms such as glutamate, migraine, N-Methyl-D-Aspartate Receptor, and NMDAR were used. No restrictions were made in terms of the language and date of publication. In animal models, administration of monosodium glutamate (MSG) activated and sensitized trigeminovascular neurons. In healthy human participants, consumption of MSG caused headaches, craniofacial sensitivity, and nausea. In in vivo models and through immunolabeling, NMDAR subunits NR1, NR2A, and NR2B were expressed in trigeminal ganglion neurons. In humans, NMDAR antagonists such as ketamine and memantine caused a significant reduction in pain intensity and monthly headache frequency. Accumulative evidence indicates that NMDAR is a promising new target for the treatment of migraine. Selective NMDAR antagonists without central effects are needed to investigate their therapeutic benefit in the treatment of migraine.
已经研发出几种用于治疗偏头痛的急性和预防性药物。然而，相当一部分患者报告疗效不佳且耐受性差，这凸显了需要新的治疗选择。谷氨酸是大脑中最重要的兴奋性神经递质，包括N-甲基-D-天冬氨酸受体（NMDAR）在内的谷氨酸受体在三叉神经血管系统的多个层面表达，而该系统是偏头痛疼痛的解剖学和生理学基础。为了综述研究NMDAR在偏头痛病理生理学中作用的临床前和临床研究。本研究未注册方案。本综述的参考文献通过对PubMed数据库的叙述性检索确定。使用了谷氨酸、偏头痛、N-甲基-D-天冬氨酸受体和NMDAR等检索词。在语言和出版日期方面没有限制。在动物模型中，给予谷氨酸钠（MSG）可激活并致敏三叉神经血管神经元。在健康人类受试者中，食用MSG会引起头痛、颅面部敏感和恶心。在体内模型中并通过免疫标记，NMDAR亚基NR1、NR2A和NR2B在三叉神经节神经元中表达。在人类中，氯胺酮和美金刚等NMDAR拮抗剂可显著降低疼痛强度和每月头痛频率。累积证据表明，NMDAR是治疗偏头痛的一个有前景的新靶点。需要无中枢作用的选择性NMDAR拮抗剂来研究它们在治疗偏头痛中的治疗益处。
