干扰素γ在眶下神经损伤大鼠脊髓三叉神经尾下核星形胶质细胞中的信号转导参与了口面部神经痛的发生

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Sayaka Asano, Akiko Okada-Ogawa, Momoyo Kobayashi, Mamiko Yonemoto, Yasushi Hojo, Ikuko Shibuta, Noboru Noma, Koichi Iwata, Suzuro Hitomi, Masamichi Shinoda
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引用次数: 0

摘要

背景:三叉神经损伤会导致口面部疼痛,从而影响日常生活。然而,其潜在机制仍不清楚,适当的治疗方法也尚未确立。本研究旨在探讨干扰素γ(IFN-γ)信号在脊髓三叉神经尾下核(Vc)中参与口面部神经病理性疼痛的情况:方法:通过部分结扎眶下神经(IONI),对大鼠进行眶下神经损伤(IONI)实验。在IONI大鼠或假大鼠身上,以及在IFN-γ和IFN-γ与氟柠檬酸盐(星形胶质细胞活化抑制剂)的混合物持续在蝶窦内给药后,或在IONI大鼠身上给药IFN-γ拮抗剂后,测量大鼠对须垫皮肤机械刺激的头退缩反射阈值(HWT)。分析了IONI或假治疗后Vc的IFN-γ受体免疫组化和IFN-γ Western印迹。在给予 IFN-γ 和 IFN-γ 与柠檬酸氟的混合物后,还分析了神经胶质纤维酸蛋白(GFAP)免疫组化和 Western 印迹。此外,还检测了IONI组、假组和服用IFN-γ拮抗剂的IONI组Vc中单个神经元活性的变化:结果:IONI后HWT下降。IONI后IFN-γ和IFN-γ受体上调,IFN-γ受体在Vc星形胶质细胞中表达。给予 IFN-γ 可降低 HWT,而 IFN-γ 和氟柠檬酸盐的混合物可恢复 HWT 的下降。IFN-γ能上调GFAP的表达,而IFN-γ和柠檬酸氟的混合物能恢复GFAP表达的上调。IONI能明显增强机械诱发反应的神经元活性,而服用IFN-γ拮抗剂能明显抑制这些活性的增强:结论:通过星形胶质细胞中的受体传递 IFN-γ 信号是与三叉神经损伤相关的口面部神经病理性疼痛的一个关键机制。这些发现将有助于开发治疗口面部神经病理性疼痛的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Involvement of interferon gamma signaling in spinal trigeminal caudal subnucleus astrocyte in orofacial neuropathic pain in rats with infraorbital nerve injury.

Background: Trigeminal nerve injury causes orofacial pain that can interfere with activities of daily life. However, the underlying mechanism remains unknown, and the appropriate treatment has not been established yet. This study aimed to examine the involvement of interferon gamma (IFN-γ) signaling in the spinal trigeminal caudal subnucleus (Vc) in orofacial neuropathic pain. Methods: Infraorbital nerve (ION) injury (IONI) was performed in rats by partial ION ligation. The head-withdrawal reflex threshold (HWT) to mechanical stimulation of the whisker pad skin was measured in IONI or sham rats, as well as following a continuous intracisterna magna administration of IFN-γ and a mixture of IFN-γ and fluorocitrate (inhibitor of astrocytes activation) in naïve rats, or an IFN-γ antagonist in IONI rats. The IFN-γ receptor immunohistochemistry and IFN-γ Western blotting were analyzed in the Vc after IONI or sham treatment. The glial fibrillary acid protein (GFAP) immunohistochemistry and Western blotting were also analyzed after administration of IFN-γ and the mixture of IFN-γ and fluorocitrate. Moreover, the change in single neuronal activity in the Vc was examined in the IONI, sham, and IONI group administered IFN-γ antagonist. Results: The HWT decreased after IONI. The IFN-γ and IFN-γ receptor were upregulated after IONI, and the IFN-γ receptor was expressed in Vc astrocytes. IFN-γ administration decreased the HWT, whereas the mixture of IFN-γ and fluorocitrate recovered the decrement of HWT. IFN-γ administration upregulated GFAP expression, while the mixture of IFN-γ and fluorocitrate recovered the upregulation of GFAP expression. IONI significantly enhanced the neuronal activity of the mechanical-evoked responses, and administration of an IFN-γ antagonist significantly inhibited these enhancements. Conclusions: IFN-γ signaling through the receptor in astrocytes is a key mechanism underlying orofacial neuropathic pain associated with trigeminal nerve injury. These findings will aid in the development of therapeutics for orofacial neuropathic pain.

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来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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