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首页> 外文期刊>The journal of pain: official journal of the American Pain Society >Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system
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Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system

机译：周围三叉神经血管系统中存储CGRP和CGRP受体的神经纤维的分化

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Primary headaches such as migraine are postulated to involve the activation of sensory trigeminal pain neurons that innervate intracranial blood vessels and the dura mater. It is suggested that local activation of these sensory nerves may involve dural mast cells as one factor in local inflammation, causing sensitization of meningeal nociceptors. Immunofluorescence was used to study the detailed distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in whole-mount rat dura mater and in human dural vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with respect to each other and in relationship to mast cells, myelin, substance P, neuronal nitric oxide synthase, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide. CGRP expression was found in thin unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity colocalized with mast cell tryptase in rodent; however, expression of both receptor components was not observed in human mast cells. Immunoreactive substance P fibers coexpressed CGRP, although neuronal nitric oxide synthase and vasoactive intestinal peptide expression was very limited, and these fibers were distinct from the CGRP-positive fibers. Few pituitary adenylate cyclase-activating polypeptide immunoreactive fibers occurred and some colocalized with CGRP. Perspective This study demonstrates the detailed distribution of CGRP and its receptor in the dura mater. These data suggest that CGRP is expressed in C-fibers and may act on A-fibers, rodent mast cells, and vascular smooth muscle cells that express the CGRP receptor. These sites represent potential pathophysiological targets of novel antimigraine agents such as the newly developed CGRP receptor antagonists.
机译：假定原发性头痛（例如偏头痛）会牵涉到支配颅内血管和硬脑膜的感觉三叉神经痛神经元的激活。提示这些感觉神经的局部活化可能将硬脑膜肥大细胞作为局部炎症的一个因素，引起脑膜伤害感受器的致敏。免疫荧光法用于研究降钙素基因相关肽（CGRP）及其受体成分降钙素受体样受体（CLR）和受体活性修饰蛋白1（RAMP1）在整个大鼠硬脑膜和人硬脑膜中的分布船只。相互评估了CGRP，CLR和RAMP1的相对分布，并与肥大细胞，髓磷脂，P物质，神经元一氧化氮合酶，垂体腺苷酸环化酶激活多肽和血管活性肠肽有关。 CGRP在细无髓纤维中发现，而CLR和RAMP1在与A纤维标记物共表达的较粗髓纤维中表达。 CLR和RAMP1免疫反应性与肥大细胞类胰蛋白酶共定位于啮齿动物中;然而，在人类肥大细胞中未观察到两种受体成分的表达。免疫反应性物质P纤维共表达CGRP，尽管神经元一氧化氮合酶和血管活性肠肽的表达非常有限，并且这些纤维与CGRP阳性纤维截然不同。很少有垂体腺苷酸环化酶激活多肽免疫反应性纤维发生，并且一些与CGRP共定位。观点这项研究证明了硬脑膜中CGRP及其受体的详细分布。这些数据表明，CGRP在C纤维中表达，并可能作用于表达CGRP受体的A纤维，啮齿动物肥大细胞和血管平滑肌细胞。这些位点代表了新型抗偏头痛药物（例如新开发的CGRP受体拮抗剂）的潜在病理生理靶标。

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