Inhibition of Nerve Growth Factor Signaling Alleviates Repeated Dural Stimulation-induced Hyperalgesia in Rats
Inhibition of Nerve Growth Factor Signaling Alleviates Repeated Dural Stimulation-induced Hyperalgesia in Rats
复制标题
抑制神经生长因子信号传导可减轻大鼠反复硬脑膜刺激引起的痛觉过敏
DOI：
10.1016/j.neuroscience.2018.12.006
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发表时间：
2019-02
期刊：
影响因子：
3.3
通讯作者：
Chen Lixue
中科院分区：
文献类型：
--
作者：
Zhou Huiru;Wang Xueying;Wang Sha;Liu Chaoyang;Fu Qingqing;Qin Guangcheng;Zhou Jiying;Chen Lixue
我们前期的研究表明三叉神经尾侧核（TNC）酸敏感离子通道3（ASIC 3）参与了复发性偏头痛的发病机制。ASIC 3受神经生长因子（NGF）调节，其在各种疼痛障碍中诱导痛觉过敏。神经生长因子的中和被认为是一种有效的治疗方法。然而，NGF对慢性偏头痛（CM）中反复偏头痛样发作的作用仍不清楚。因此，本研究探讨了NGF对TNC中ASIC 3表达的影响以及NGF信号在化学性硬脑膜刺激诱导的痛觉过敏中的作用。通过连续7天反复硬脑膜灌注炎性汤（IS）来建立大鼠模型，以模拟CM发作。重复注射IS后，大鼠眶周区域和后爪出现皮肤痛觉过敏，表现出明显较低的痛阈。注射IS后，TNC神经元中NGF的mRNA和蛋白表达上调，且NGF主要表达于胞浆。侧脑室注射抗神经生长因子中和抗体可减轻CM大鼠的皮肤痛觉过敏，并降低TNC中蛋白激酶C（PKC）、ASIC 3、降钙素基因相关肽（CGRP）和c-Fos的表达。此外，侧脑室注射PKC阻断剂chelerythrine chloride减轻了IS灌注诱导的痛觉过敏，并降低了TNC中ASIC 3，CGRP和c-Fos水平。这些结果表明，NGF可能通过反复刺激IS硬脑膜后TNC中的PKC活性调节ASIC 3的表达，该信号通路可能参与了IS诱导的痛敏。
Our previous study showed that acid-sensing ion channel 3 (ASIC3) in the trigeminal nucleus caudalis (TNC) is involved in the pathogenesis of recurrent migraine. ASIC3 is regulated by nerve growth factor (NGF), which induces hyperalgesia in various pain disorders. Neutralization of NGF is considered an effective treatment method. However, the contribution of NGF to repeated migraine-like attacks in chronic migraine (CM) remains unclear. Therefore, this study investigated the effect of NGF on ASIC3 expression in the TNC and the role of NGF signaling in chemical dural stimulation-induced hyperalgesia. A rat model was established by repeated dural infusions of inflammatory soup (IS) for seven days to simulate CM attacks. After repeated IS infusions, cutaneous hyperalgesia appeared in the rats’ periorbital region and hind paws, which showed significantly lower pain thresholds. IS infusions upregulated the mRNA and protein of NGF in the TNC, and NGF was mainly expressed in the cytoplasm of TNC neurons. An intracerebroventricular injection of an anti-NGF-neutralizing antibody relieved the cutaneous hyperalgesia of CM rats and decreased protein kinase C (PKC), ASIC3, calcitonin gene-related peptide (CGRP) and c-Fos expression in the TNC. Moreover, intracerebroventricular injection with the PKC blocker chelerythrine chloride alleviated IS infusion-induced hyperalgesia and reduced ASIC3, CGRP and c-Fos levels in the TNC. These results indicate that NGF might regulate ASIC3 expression via PKC activity in the TNC following repeated IS dural stimulation, and this signaling pathway might participate in IS-induced hyperalgesia.
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影响因子：
5.1
作者：
Kashyap MP;Roberts C;Waseem M;Tyagi P
通讯作者：
Tyagi P
影响因子：
3.4
作者：
G. Leanza;G. Leanza;O. Nilsson;R. Wiley;A. Björklund
通讯作者：
G. Leanza;G. Leanza;O. Nilsson;R. Wiley;A. Björklund
影响因子：
4.8
作者：
Mamet, J;Lazdunski, M;Voilley, N
通讯作者：
Voilley, N
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
7.4
作者：
Majuta LA;Guedon JG;Mitchell SAT;Ossipov MH;Mantyh PW
通讯作者：
Mantyh PW