Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
J Headache Pain. 2024 Sep 20;25(1):156. doi: 10.1186/s10194-024-01864-6.
Chronic migraine is a severe and common neurological disorder, yet its precise physiological mechanisms remain unclear. The IGF1/IGF1r signaling pathway plays a crucial role in pain modulation. Studies have shown that IGF1, by binding to its receptor IGF1r, activates a series of downstream signaling cascades involved in neuronal survival, proliferation, autophagy and functional regulation. The activation of these pathways can influence nociceptive transmission. Furthermore, alterations in IGF1/IGF1r signaling are closely associated with the development of various chronic pain conditions. Therefore, understanding the specific mechanisms by which this pathway contributes to pain is of significant importance for the development of novel pain treatment strategies. In this study, we investigated the role of IGF1/IGF1r and its potential mechanisms in a mouse model of chronic migraine.
Chronic migraine was induced in mice by repeated intraperitoneal injections of nitroglycerin. Mechanical and thermal hypersensitivity responses were assessed using Von Frey filaments and radiant heat, respectively. To determine the role of IGF1/IGF1r in chronic migraine (CM), we examined the effects of the IGF1 receptor antagonist ppp (Picropodophyllin) on pain behaviors and the expression of calcitonin gene-related peptide (CGRP) and c-Fos.
In the nitroglycerin-induced chronic migraine model in mice, neuronal secretion of IGF1 is elevated within the trigeminal nucleus caudalis (TNC). Increased phosphorylation of the IGF1 receptor occurs, predominantly co-localizing with neurons. Treatment with ppp alleviated basal mechanical hypersensitivity and acute mechanical allodynia. Furthermore, ppp ameliorated autophagic dysfunction and reduced the expression of CGRP and c-Fos.
Our findings demonstrate that in the chronic migraine (CM) model in mice, there is a significant increase in IGF1 expression in the TNC region. This upregulation of IGF1 leads to enhanced phosphorylation of IGF1 receptors on neurons. Targeting and inhibiting this signaling pathway may offer potential preventive strategies for mitigating the progression of chronic migraine.
慢性偏头痛是一种严重且常见的神经疾病，但确切的生理机制仍不清楚。IGF1/IGF1r 信号通路在疼痛调节中起着关键作用。研究表明，IGF1 通过与其受体 IGF1r 结合，激活一系列涉及神经元存活、增殖、自噬和功能调节的下游信号级联反应。这些途径的激活会影响伤害性传递。此外，IGF1/IGF1r 信号的改变与各种慢性疼痛疾病的发展密切相关。因此，了解该途径促进疼痛的具体机制对于开发新的疼痛治疗策略具有重要意义。在本研究中，我们研究了 IGF1/IGF1r 及其在慢性偏头痛小鼠模型中的潜在机制。
通过重复腹腔注射硝化甘油诱导慢性偏头痛。使用 Von Frey 纤维和辐射热分别评估机械和热超敏反应。为了研究 IGF1/IGF1r 在慢性偏头痛（CM）中的作用，我们研究了 IGF1 受体拮抗剂 ppp（Picropodophyllin）对疼痛行为和降钙素基因相关肽（CGRP）和 c-Fos 表达的影响。
在小鼠硝化甘油诱导的慢性偏头痛模型中，三叉神经尾核（TNC）内的 IGF1 神经元分泌增加。IGF1 受体的磷酸化增加，主要与神经元共定位。ppp 治疗可减轻基础机械性超敏反应和急性机械性痛觉过敏。此外，ppp 改善了自噬功能障碍，并降低了 CGRP 和 c-Fos 的表达。
我们的研究结果表明，在慢性偏头痛（CM）小鼠模型中，TNC 区域的 IGF1 表达显著增加。IGF1 的这种上调导致神经元上 IGF1 受体的磷酸化增强。靶向和抑制这种信号通路可能为减轻慢性偏头痛的进展提供潜在的预防策略。
