Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, 20246, Hamburg, Germany.
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), 635 Charles Young Drive, Los Angeles, CA, 90095, USA.
Neurotherapeutics. 2018 Apr;15(2):361-370. doi: 10.1007/s13311-018-0616-5.
There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling. Animal studies indicate that glutamate plays a key role in pain transmission, central sensitization, and cortical spreading depression. Multiple therapies that target glutamate receptors including magnesium, topiramate, memantine, and ketamine have been reported to have efficacy in the treatment of migraine, although with the exception of topiramate, the evidence for the efficacy of these therapies is not strong. Also, because all of these therapies have other mechanisms of action, it is not possible to conclude that the efficacy of these drugs is entirely due to their effects on glutamate receptors. Further studies are needed to more clearly delineate the possible roles of glutamate and its specific receptor subtypes in migraine and to identify new ways of targeting glutamate for migraine therapy.
有大量证据表明谷氨酸在偏头痛中起作用。谷氨酸水平在偏头痛患者的大脑中较高，在周围循环中也可能较高，特别是在发作期间。偏头痛患者的内源性谷氨酸受体调节剂犬尿氨酸的血液水平发生改变。人群遗传学研究表明，与谷氨酸信号有关的基因参与偏头痛，而导致家族性偏瘫性偏头痛和其他家族性偏头痛综合征的基因突变可能会影响谷氨酸信号。动物研究表明，谷氨酸在疼痛传递、中枢敏化和皮质扩散性抑制中起关键作用。多种靶向谷氨酸受体的治疗方法，包括镁、托吡酯、美金刚和氯胺酮，已被报道对偏头痛的治疗有效，尽管除了托吡酯之外，这些治疗方法的疗效证据并不强。此外，由于所有这些治疗方法都有其他作用机制，因此不能得出这些药物的疗效完全归因于它们对谷氨酸受体的影响。还需要进一步的研究来更清楚地阐明谷氨酸及其特定受体亚型在偏头痛中的可能作用，并确定针对谷氨酸治疗偏头痛的新方法。
