Scuteri Damiana, Martelletti Paolo
Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
School of Health, Unitelma Sapienza University of Rome, 00161 Rome, Italy.
Toxins (Basel). 2025 Jul 17;17(7):355. doi: 10.3390/toxins17070355.
Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies.
偏头痛是一种以神经源性炎症为特征的神经血管性发作性疾病，对生活质量有显著影响。美国食品药品监督管理局（FDA）于2010年批准A型肉毒毒素用于慢性偏头痛的预防性治疗。如今，在其应用的第四个十年里，它在100个国家被批准用于15种主要适应症。其作用机制基于抑制初级感觉神经元释放神经递质，非常复杂：它具有抗伤害感受作用，但对神经性疼痛状况也有镇痛效果，并减少了急救药物的需求。人们已经研究了基因变异在偏头痛的发病机制、临床表型以及对治疗反应中的潜在作用。这些研究主要涉及与血管调节和心血管病理相关的基因，包括编码血管紧张素转换酶（ACE）和亚甲基四氢叶酸还原酶（MTHFR）的基因。然而，就理解偏头痛易感性、先兆、慢性化以及对症状性和预防性治疗反应所涉及的机制而言，表观遗传学，尤其是基因和表观遗传修饰仍研究不足。特别是，本研究的目的是收集有关影响降钙素基因相关肽（CGRP）途径的基因变异和表观遗传修饰的证据，CGRP是A型肉毒毒素和所有新型单克隆抗体的作用靶点。
