Loewendorf Andrea I, Matynia Anna, Saribekyan Hakob, Gross Noah, Csete Marie, Harrington Mike
Huntington Medical Research Institutes , Pasadena, CA , USA.
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Front Immunol. 2016 Apr 19;7:140. doi: 10.3389/fimmu.2016.00140. eCollection 2016.
Migraine is a common, little understood, and debilitating disease. It is much more prominent in women than in men (~2/3 are women) but the reasons for female preponderance are not clear. Migraineurs frequently experience severe comorbidities, such as allergies, depression, irritable bowel syndrome, and others; many of the comorbidities are more common in females. Current treatments for migraine are not gender specific, and rarely are migraine and its comorbidities considered and treated by the same specialist. Thus, migraine treatments represent a huge unmet medical need, which will only be addressed with greater understanding of its underlying pathophysiology. We discuss the current knowledge about sex differences in migraine and its comorbidities, and focus on the potential role of mast cells (MCs) in both. Sex-based differences in pain recognition and drug responses, fluid balance, and the blood-brain barrier are recognized but their impact on migraine is not well studied. Furthermore, MCs are well recognized for their prominent role in allergies but much less is known about their contributions to pain pathways in general and migraine specifically. MC-neuron bidirectional communication uniquely positions these cells as potential initiators and/or perpetuators of pain. MCs can secrete nociceptor sensitizing and activating agents, such as serotonin, prostaglandins, histamine, and proteolytic enzymes that can also activate the pain-mediating transient receptor potential vanilloid channels. MCs express receptors for both estrogen and progesterone that induce degranulation upon binding. Furthermore, environmental estrogens, such as Bisphenol A, activate MCs in preclinical models but their impact on pain pathways or migraine is understudied. We hope that this discussion will encourage scientists and physicians alike to bridge the knowledge gaps linking sex, MCs, and migraine to develop better, more comprehensive treatments for migraine patients.
偏头痛是一种常见但了解甚少且使人虚弱的疾病。女性患者比男性患者更为突出（约三分之二为女性），但其女性居多的原因尚不清楚。偏头痛患者经常伴有严重的合并症，如过敏、抑郁、肠易激综合征等；其中许多合并症在女性中更为常见。目前针对偏头痛的治疗并非针对性别，而且偏头痛及其合并症很少由同一位专科医生进行诊断和治疗。因此，偏头痛的治疗存在巨大的未满足医疗需求，只有更深入地了解其潜在的病理生理学才能解决这一问题。我们讨论了目前关于偏头痛及其合并症性别差异的知识，并重点关注肥大细胞在两者中的潜在作用。基于性别的疼痛识别、药物反应、体液平衡和血脑屏障差异已得到认可，但它们对偏头痛的影响尚未得到充分研究。此外，肥大细胞在过敏中的突出作用已广为人知，但它们对一般疼痛通路尤其是偏头痛的贡献却知之甚少。肥大细胞与神经元之间的双向通讯使这些细胞成为疼痛的潜在引发者和/或维持者。肥大细胞可以分泌伤害感受器致敏和激活剂，如血清素、前列腺素、组胺和蛋白水解酶，这些物质也可以激活介导疼痛的瞬时受体电位香草酸通道。肥大细胞表达雌激素和孕激素的受体，结合后会诱导脱颗粒。此外，环境雌激素，如双酚A，在临床前模型中可激活肥大细胞，但其对疼痛通路或偏头痛的影响尚未得到充分研究。我们希望这次讨论能够鼓励科学家和医生填补将性别、肥大细胞和偏头痛联系起来的知识空白，从而为偏头痛患者开发出更好、更全面的治疗方法。
Zotero 插件
