Regulation of transient receptor potential vanilloid 1 expression in trigeminal ganglion neurons via methyl-CpG binding protein 2 signaling contributes tongue heat sensitivity and inflammatory hyperalgesia in mice.
Regulation of transient receptor potential vanilloid 1 expression in trigeminal ganglion neurons via methyl-CpG binding protein 2 signaling contributes tongue heat sensitivity and inflammatory hyperalgesia in mice.
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DOI：
10.1177/1744806916633206
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Iwata K
中科院分区：
文献类型：
--
作者：
Suzuki A;Shinoda M;Honda K;Shirakawa T;Iwata K
在Rett综合征患者中已经报道了疼痛痛觉减退，Rett综合征是一种严重的神经发育障碍，其可归因于甲基-CpG结合蛋白2（MeCP 2）的突变。在这里，我们使用Mecp 2杂合（Mecp 2 +/−）小鼠研究了MeCP 2信号在正常和炎症状态下舌热敏感性中的作用。舌的热痛觉减退发生在Mecp 2 +/−小鼠中，并且将完全弗氏佐剂粘膜下注射到舌中在野生型小鼠的发炎部位产生了持久的热痛觉过敏，但在Mecp 2 +/−小鼠中没有。瞬时受体电位香草酸1在野生型和Mecp 2 +/−小鼠中大量支配舌的MeCP 2免疫反应性三叉神经节神经元中表达（野生型70.9%; Mecp 2 +/− 72.1%）。相对于野生型小鼠，Mecp 2 +/−小鼠中支配舌的瞬时受体电位香草素1免疫反应性三叉神经节神经元的数量较少（野生型为30.5%; Mecp 2 +/−为20.2%）。在完全弗氏佐剂注射后，支配舌的瞬时受体电位香草素1和MeCP 2免疫反应性三叉神经节神经元的数量以及三叉神经节中MeCP 2蛋白的表达在野生型小鼠中显著增加，但在Mecp 2 +/−小鼠中没有。此外，舌热痛觉过敏后完全弗氏佐剂注射完全抑制SB 366791，瞬时受体电位香草素1拮抗剂，在舌头上。这些研究结果表明，舌头的热敏感性和超敏反应依赖于瞬时受体电位香草酸1的表达，这是通过MeCP 2信号在三叉神经节神经元支配舌头调节。
Pain hypoalgesia has been reported in Rett syndrome patients, a severe neurodevelopmental disorder which can be attributed to mutations in the methyl-CpG binding protein 2 (MeCP2). Here, we examined the role of MeCP2 signaling in tongue heat sensitivity in the normal and inflamed state using Mecp2 heterozygous (Mecp2+/−) mice. Heat hypoalgesia of the tongue occurred in Mecp2+/− mice and submucosal injection of complete Freund’s adjuvant into the tongue produced a long-lasting heat hyperalgesia at the inflamed site in wild-type mice but not in Mecp2+/− mice. Transient receptor potential vanilloid 1 was expressed in a large number of MeCP2-immunoreactive trigeminal ganglion neurons innervating the tongue in both wild-type and Mecp2+/− mice (70.9% in wild type; 72.1% in Mecp2+/−). The number of transient receptor potential vanilloid 1-immunoreactive trigeminal ganglion neurons innervating the tongue was smaller in Mecp2+/− mice relative to wild-type mice (30.5% in wild type; 20.2% in Mecp2+/−). Following complete Freund’s adjuvant injection, the number of transient receptor potential vanilloid 1- and MeCP2-immunoreactive trigeminal ganglion neurons innervating the tongue, as well as MeCP2 protein expression in trigeminal ganglion, was significantly increased in wild-type mice but not in Mecp2+/− mice. Additionally, tongue heat hyperalgesia following complete Freund’s adjuvant injection was completely suppressed by the administration of SB366791, a transient receptor potential vanilloid 1 antagonist, in the tongue. These findings indicate that tongue heat sensitivity and hypersensitivity are dependent on the expression of transient receptor potential vanilloid 1 which is regulated via MeCP2 signaling in trigeminal ganglion neurons innervating the tongue.