Background

Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents.

Methods

The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments.

Results

Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in numerous small to medium-sized neurons and thick axons characteristic of A∂ sensory fibers. Double immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and calcitonin gene-related peptide. In contrast, double immunostaining showed expression of the calcitonin gene-related peptide receptor component receptor activity-modifying protein 1 and oxytocin receptors in 23% of the small cells and in 47% of the medium-sized cells. Oxytocin immunofluorescence was observed only in trigeminal ganglia satellite glial cells. Oxytocin mRNA was below detection limit in the trigeminal ganglia. The trigeminal nucleus caudalis expressed mRNA for both oxytocin and its receptor. K⁺-evoked calcitonin gene-related peptide release from either isolated trigeminal ganglia or dura mater and it was not significantly affected by oxytocin (10 µM). Oxytocin directly constricted cranial arteries ex vivo (pEC₅₀ ∼ 7); however, these effects were inhibited by the vasopressin V_1A antagonist SR49059.

Conclusion

Oxytocin receptors are extensively expressed throughout the rat trigeminovascular system and in particular in trigeminal ganglia A∂ neurons and fibers, but no functional oxytocin receptors were demonstrated in the dura and cranial arteries. Thus, circulating oxytocin may act on oxytocin receptors in the trigeminal ganglia to affect nociception transmission. These effects may help explain hormonal influences in migraine and offer a novel way for treatment.

中文翻译：

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催产素作为三叉神经血管系统中的调节神经肽：催产素和催产素受体的定位、表达和功能。

背景

最近的临床发现表明，催产素可能是偏头痛的一种新疗法。然而，人们对这种神经肽/激素及其受体在三叉神经血管通路中的作用知之甚少。在这里，我们确定了大鼠三叉神经节中催产素和催产素受体的表达、定位和功能，以及外周（硬脑膜和颅动脉）和中枢（三叉神经尾核）传入神经的靶标。

方法

这些方法包括免疫组织化学、信使 RNA 测量、定量 PCR、降钙素基因相关肽的释放和动脉节段的肌造影。

结果

催产素受体 mRNA 在大鼠三叉神经节中表达，受体蛋白定位于众多中小神经元和 A∂ 感觉纤维特征的粗轴突中。双免疫组化显示只有少数神经元同时表达催产素受体和降钙素基因相关肽。相比之下，双重免疫染色显示降钙素基因相关肽受体成分受体活性修饰蛋白 1 和催产素受体在 23% 的小细胞和 47% 的中型细胞中表达。仅在三叉神经节卫星神经胶质细胞中观察到催产素免疫荧光。三叉神经节中的催产素 mRNA 低于检测限。三叉神经尾核表达催产素及其受体的mRNA。K ⁺-诱发的降钙素基因相关肽从分离的三叉神经节或硬脑膜中释放，并且它不受催产素 (10 µM) 的显着影响。催产素在体外直接收缩颅动脉（pEC ₅₀  ∼ 7）；然而，这些作用被加压素 V _1A拮抗剂 SR49059 抑制。

结论

催产素受体在大鼠三叉神经血管系统中广泛表达，特别是在三叉神经节 A∂ 神经元和纤维中，但在硬脑膜和颅动脉中没有表现出功能性催产素受体。因此，循环中的催产素可能作用于三叉神经节中的催产素受体，从而影响伤害感受的传递。这些影响可能有助于解释偏头痛中的激素影响，并提供一种新的治疗方法。