Migraine is an extraordinarily prevalent and disabling headache disorder that affects one billion people worldwide. Throbbing pain is one of several migraine symptoms including sensitivity to light (photophobia), sometimes to sounds, smell and touch. The basic mechanisms underlying migraine remain inadequately understood, and current treatments (with triptans being the primary standard of care) are not well tolerated by some patients. NOP (Nociceptin OPioid) receptors, the fourth member of the opioid receptor family, are expressed in the brain and periphery with particularly high expression known to be in trigeminal ganglia (TG). The aim of our study was to further explore the involvement of the NOP receptor system in migraine. To this end, we used immunohistochemistry to examine NOP receptor distribution in TG and trigeminal nucleus caudalus (TNC) in mice, including colocalization with specific cellular markers, and used nitroglycerin (NTG) models of migraine to assess the influence of the selective NOP receptor agonist, Ro 64-6198, on NTG-induced pain (sensitivity of paw and head using von Frey filaments) and photophobia in mice. Our immunohistochemical studies with NOP-eGFP knock-in mice indicate that NOP receptors are on the majority of neurons in the TG and are also very highly expressed in the TNC. In addition, Ro 64-6198 can dose dependently block NTG-induced paw and head allodynia, an effect that is blocked by the NOP antagonist, SB-612111. Moreover, Ro 64-6198, can decrease NTG-induced light sensitivity in mice. These results suggest that NOP receptor agonists should be futher explored as treatment for migraine symptoms. This article is part of the special issue on Neuropeptides.

中文翻译：

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NOP受体激动剂可减轻小鼠硝酸甘油诱导的偏头痛样症状。

偏头痛是一种极为普遍的致残性头痛病，全世界有十亿人受到影响。阵痛是偏头痛的几种症状之一，包括对光的敏感（畏光），有时对声音，气味和触觉。偏头痛的基本机制仍未得到足够的了解，某些患者对目前的治疗方法（曲坦类药物为主要治疗标准）还没有很好的耐受性。NOP（Nociceptin阿片样物质）受体，是阿片样物质受体家族的第四个成员，在脑和周围组织中以三叉神经节（TG）的高表达表达。我们研究的目的是进一步探索偏头痛中NOP受体系统的参与。为此，我们使用免疫组化方法检查了TG和小鼠三叉神经核（TNC）中NOP受体的分布，包括与特定细胞标志物的共定位，并使用偏头痛的硝化甘油（NTG）模型评估了选择性NOP受体激动剂Ro 64- 6198，关于NTG引起的小鼠疼痛（使用von Frey细丝的爪子和头部的敏感性）和畏光。我们对NOP-eGFP敲入小鼠的免疫组织化学研究表明，NOP受体在TG中的大多数神经元上，并且在TNC中也高度表达。此外，Ro 64-6198可以剂量依赖性地阻断NTG诱导的爪和头部异常性疼痛，这一作用被NOP拮抗剂SB-612111阻断。此外，Ro 64-6198可以降低NTG诱导的小鼠光敏感性。这些结果表明，应进一步探索NOP受体激动剂作为偏头痛症状的治疗方法。本文是有关神经肽的特刊的一部分。