Chen Ting-Bin, Yang Cheng-Chia, Tsai I-Ju, Yang Hao-Wen, Hsu Yung-Chu, Chang Ching-Mao, Yang Chun-Pai
Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan.
Department of Healthcare Administration, Asia University, Taichung, Taiwan.
Front Neurol. 2024 May 6;15:1366372. doi: 10.3389/fneur.2024.1366372. eCollection 2024.
Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.
偏头痛是一种在全球范围内高度流行的疾病，给个人和社会带来了巨大的临床和经济负担。目前的治疗方法疗效和可接受性有限，这凸显了对更有效、更安全的预防方法的需求，包括使用营养保健品来治疗偏头痛。偏头痛涉及中枢神经系统和外周神经系统之间的相互作用，在疼痛产生和传递过程中，三叉神经血管系统（TVS）会有显著的激活和致敏。这种疾病受遗传易感性和环境因素的影响，导致感觉处理发生改变。神经炎症反应日益被认为是偏头痛病理生理学的关键事件，涉及复杂的神经-胶质-血管相互作用。这种相互作用部分由降钙素基因相关肽（CGRP）、垂体腺苷酸环化酶激活多肽（PACAP）等神经肽和/或皮质扩散性抑制（CSD）介导，涉及氧化应激、线粒体功能障碍、含NOD样受体家族pyrin结构域蛋白3（NLRP3）炎性小体形成、活化的小胶质细胞和反应性星形胶质细胞。ω-3多不饱和脂肪酸（PUFAs），特别是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），对神经系统至关重要，介导多种生理功能。ω-3 PUFAs因其强大的抗炎、抗伤害感受、抗氧化和神经调节特性，对心血管、神经和精神方面有益，这些特性可调节神经炎症、神经源性炎症、疼痛传递、增强线粒体稳定性和调节情绪。此外，专门的促消退介质（SPMs），一类源自PUFA的脂质介质，调节促炎和消退途径，发挥重要的抗炎和神经作用，这反过来可能有助于缓解偏头痛的症状。ω-3 PUFAs影响多种神经生物学途径，且已证明缺乏重大不良事件，这突出了它们在偏头痛管理中的多方面作用和安全性。尽管并非所有ω-3 PUFAs试验都显示对减轻偏头痛症状有益，但仍需要进一步研究来充分确立它们的临床疗效，并了解ω-3 PUFAs和源自PUFA的脂质介质SPMs对偏头痛病理生理学和进展产生影响的精确分子机制。这篇综述强调了它们在调节脑功能（如神经免疫效应）方面的潜力，并表明它们有望成为有效的偏头痛预防候选药物。
