Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, 91054 Erlangen, Germany.
Brain. 2009 Nov;132(Pt 11):3134-41. doi: 10.1093/brain/awp168. Epub 2009 Sep 8.
Several lines of evidence suggest a major role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine and other primary headaches. Inhibition of CGRP receptors by olcegepant and telcagepant has been successfully used to treat acute migraine and to reduce the activity of spinal trigeminal neurons involved in meningeal nociception in rodents. The site of CGRP receptor inhibition is unclear, however. In adult Wistar rats anaesthetized with isofluorane systemic intravenous infusion (0.9 mg/kg) or unilateral facial injection (1 mM in 100 microl) of capsaicin was used to induce activity in the trigeminal nociceptive system. Animals were pre-treated either by saline or olcegepant. In comparison with vehicle infusion or the non-injected side of the face, capsaicin significantly increased the expression of the activation markers Fos in the spinal trigeminal nucleus and phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion. Pre-treatment with olcegepant (900 microg/kg) inhibited the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion was not changed by olcegepant pre-treatment. CGRP receptor inhibition, which has been shown to decrease spinal trigeminal activity, is likely to occur in the central nervous system rather than in the periphery including the trigeminal ganglion. This may be important for future therapeutic interventions with CGRP receptor antagonists in migraine.
有几条证据表明降钙素基因相关肽（CGRP）在偏头痛和其他原发性头痛的发病机制中起主要作用。奥昔拉肽和telcagepant 抑制 CGRP 受体已成功用于治疗急性偏头痛，并减少了参与啮齿动物脑膜伤害感受的脊髓三叉神经神经元的活性。然而，CGRP 受体抑制的部位尚不清楚。在异氟烷全身静脉输注（0.9 mg/kg）或单侧面部注射（1 mM 在 100 微升）辣椒素麻醉的成年 Wistar 大鼠中，用于诱导三叉神经伤害感受系统的活性。动物预先用盐水或奥昔拉肽处理。与载体输注或面部的未注射侧相比，辣椒素显着增加了脊髓三叉神经核中激活标记物 Fos 和三叉神经节中磷酸化细胞外信号调节激酶的表达。奥昔拉肽（900 µg/kg）预处理通过 57%抑制了整个脊髓三叉神经核中辣椒素诱导的 Fos 表达。相比之下，奥昔拉肽预处理不会改变三叉神经节中磷酸化细胞外信号调节激酶的表达。已经表明抑制 CGRP 受体可降低脊髓三叉神经活性，这可能发生在中枢神经系统而不是包括三叉神经节在内的外周。这对于未来偏头痛中 CGRP 受体拮抗剂的治疗干预可能很重要。
