Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.
Cephalalgia. 2020 Oct;40(12):1283-1295. doi: 10.1177/0333102420929027. Epub 2020 Jun 2.
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.
The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments.
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 (pEC ∼ 7); however, these effects were inhibited by the vasopressin V antagonist SR49059.
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.
最近的临床发现表明，催产素可能成为偏头痛的一种新的治疗方法。然而，这种神经肽/激素及其受体在三叉血管途径中的作用知之甚少。在这里，我们确定了催产素和催产素受体在大鼠三叉神经节中的表达、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）传入的靶标。
该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段的肌描记法。
催产素受体 mRNA 在大鼠三叉神经节中表达，受体蛋白定位于许多小到中等大小的神经元和 A∂感觉纤维特有的粗轴突。双重免疫组织化学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%的中细胞中表达。催产素免疫荧光仅在三叉神经节卫星神经胶质细胞中观察到。三叉神经节中催产素 mRNA 低于检测限。三叉神经尾核表达了催产素及其受体的 mRNA。从分离的三叉神经节或硬脑膜中，K 诱发降钙素基因相关肽释放，催产素（10μM）对其没有明显影响。催产素直接收缩颅动脉（pEC∼7）；然而，这些作用被血管加压素 V 拮抗剂 SR49059 抑制。
催产素受体广泛表达于大鼠三叉血管系统，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未发现功能性催产素受体。因此，循环催产素可能作用于三叉神经节中的催产素受体，影响痛觉传递。这些作用可能有助于解释偏头痛中的激素影响，并为治疗提供新途径。
