Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Department of Epidemiology and Health Promotion, New York University College of Dentistry, New York, USA.
J Headache Pain. 2019 Feb 14;20(1):18. doi: 10.1186/s10194-019-0968-1.
Administration of endogenous mediators or exogenous chemicals in migraine patients provoke early headaches and delayed migraine-like attacks. Although migraine provoking substances are normally vasodilators, dilation of arterial vessels does not seem to be the sole contributing factor, and the underlying mechanisms of the delayed migraine pain are mostly unknown. Sustained mechanical allodynia is a common response associated with the local administration of various proalgesic substances in experimental animals and humans. Here, we investigated the ability of a series of endogenous mediators which provoke or do not provoke migraine in patients, to cause or not cause mechanical allodynia upon their injection in the mouse periorbital area.
Mechanical allodynia was assessed with the von Frey filament assay. Stimuli were given by subcutaneous injection in the periorbital area of C57BL/6J mice; antagonists were administered by local and systemic injections.
Calcitonin gene related peptide (CGRP), but not adrenomedullin and amylin, pituitary adenylyl cyclase activating peptide (PACAP), but not vasoactive intestinal polypeptide (VIP), histamine, prostaglandin E (PGE) and prostacyclin (PGI), but not PGF evoked a dose-dependent periorbital mechanical allodynia. The painful responses were attenuated by systemic or local (periorbital) administration of antagonists for CGRP (CLR/RAMP1), PACAP (PAC-1), histamine H, PGE (EP), and PGI (IP) receptors, respectively.
The correspondence between substances that provoke (CGRP; PACAP, histamine, PGE, PGI), or do not provoke (VIP and PGF), migraine-like attacks in patients and periorbital allodynia in mice suggests that the study of allodynia in mice may provide information on the proalgesic mechanisms of migraine-provoking agents in humans. Results underline the ability of migraine-provoking substances to initiate mechanical allodynia by acting on peripheral terminals of trigeminal afferents.
在偏头痛患者中给予内源性介质或外源性化学物质会引发早期头痛和延迟性偏头痛样发作。尽管偏头痛诱发物质通常是血管扩张剂，但血管扩张似乎不是唯一的促成因素，延迟性偏头痛疼痛的潜在机制在很大程度上尚不清楚。持续机械性痛觉过敏是一种常见的反应，与在实验动物和人类中局部给予各种致痛物质有关。在这里，我们研究了一系列在患者中引发或不引发偏头痛的内源性介质，在注射到小鼠眶周区域后是否会引起或不引起机械性痛觉过敏。
使用 von Frey 细丝测定法评估机械性痛觉过敏。刺激通过皮下注射到 C57BL/6J 小鼠的眶周区域给予；拮抗剂通过局部和全身注射给予。
降钙素基因相关肽（CGRP），而不是肾上腺髓质素和淀粉样蛋白，垂体腺苷酸环化酶激活肽（PACAP），而不是血管活性肠肽（VIP），组胺，前列腺素 E（PGE）和前列环素（PGI），但不是 PGF 引起了剂量依赖性的眶周机械性痛觉过敏。疼痛反应分别通过全身或局部（眶周）给予 CGRP（CLR/RAMP1）、PACAP（PAC-1）、组胺 H、PGE（EP）和 PGI（IP）受体的拮抗剂而减弱。
在患者中引发（CGRP；PACAP、组胺、PGE、PGI）或不引发（VIP 和 PGF）偏头痛样发作的物质与在小鼠中引发眶周痛觉过敏的物质之间的对应关系表明，在小鼠中研究痛觉过敏可能为人类偏头痛诱发剂的致痛机制提供信息。结果强调了偏头痛诱发物质通过作用于三叉神经传入末梢起始机械性痛觉过敏的能力。
