1 Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Cephalalgia. 2018 Oct;38(11):1716-1730. doi: 10.1177/0333102417748563. Epub 2017 Dec 13.
Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.
背景 根据偏头痛的神经血管理论，三叉血管系统的激活有助于偏头痛的发展。本研究考察了慢性腹腔内给予生长激素释放肽（150µg/kg）对间歇性注射 10mg/kg 硝酸甘油诱导的慢性偏头痛发展的影响。
方法 在第 1、3、5、7、9 和 11 天，通过 von Frey 毛发和尾巴浸入试验分别评估基线和药物后（硝酸甘油注射后 2 小时）的机械和热敏感性。此外，我们通过使用双室条件性位置厌恶范式研究了生长激素释放肽治疗对硝酸甘油诱导的厌恶行为的影响。在行为测试结束时，即第 11 天，处死动物并使用大鼠特异性酶联免疫吸附测定试剂盒测量降钙素基因相关肽的血浆浓度。还使用实时聚合酶链反应定量三叉神经节中降钙素基因相关肽和瞬时受体电位香草醛 1 的 mRNA 表达。
结果 我们的结果表明，硝酸甘油激活了三叉血管系统，这反映在机械和热敏性增加以及降钙素基因相关肽和瞬时受体电位香草醛 1 的 mRNA 表达增加上，这些都是偏头痛的标志物，以及血浆降钙素基因相关肽水平。此外，慢性硝酸甘油注射引起条件性位置厌恶和体重减轻。然而，生长激素释放肽调节了硝酸甘油触发的瞬时受体电位香草醛 1 和降钙素基因相关肽表达的变化，并减轻了硝酸甘油诱导的痛觉过敏。
结论 这些结果首次提供了令人信服的证据，表明生长激素释放肽对慢性间歇性硝酸甘油引起的中枢敏化具有调节作用，其镇痛作用可能与三叉神经节中这些因子的减少有关。
