Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model
Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model
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Spexin/NPQ 在小鼠模型中诱导 FBJ 骨肉瘤癌基因 (Fos) 并对炎症性疼痛产生镇痛作用
DOI：
10.1016/j.ajpath.2018.12.009
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发表时间：
2019-04-01
影响因子：
6
通讯作者：
Wang, Yan-Dong
中科院分区：
文献类型：
--
作者：
Lv, Shuang-Yu;Cui, Binbin;Wang, Yan-Dong
Spexin/NPQ是一种新的高度保守的神经肽。它在外周和中枢神经系统中有广泛的表达。然而，中枢spexin对急性炎性疼痛的作用仍然未知。本研究旨在探讨脊髓上注射Spexin对炎性痛的影响及其机制。小鼠福尔马林试验的结果表明，在晚期和早期阶段，静脉注射spexin减少了滴答声/叮咬时间。非酰胺化spexin对疼痛反应没有影响。spexin的镇痛作用可被甘丙肽受体3拮抗剂SNAP 37889阻断。注射spexin后，脑内Galr 3和Adcy 4 mRNA水平升高。Spexin的镇痛作用可被阿片受体拮抗剂纳洛酮和K-阿片受体拮抗剂nor-binaltorphimine dihydrochloride完全逆转。Spexin上调强啡肽和x-阿片受体基因和蛋白表达。PCR芯片分析和实时荧光定量PCR分析表明spexin上调FBJ骨肉瘤癌基因（Fos）的mRNA水平。T-5224是c FBJ骨肉瘤癌基因（c-Fos）/激活蛋白1（AP-1）的抑制剂，可阻断spexin诱导的Pdyn和Oprkl mRNA水平的升高。I. C. V. spexin（2.43 mg/kg）使中脑导水管周围灰质大部分亚区c-Fos阳性神经元数目增加。此外，在醋酸扭体实验中，腹腔注射spexin可产生镇痛作用。我们的研究结果表明spexin可能是一种新的神经肽，对急性炎症痛具有抗伤害性作用。
Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that i.c.v. administration of spexin decreased ticking/ biting time during the late and early phases. The nonamidated spexin had no effect on pain response. The antinociception of spexin was blocked by galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by opioid receptor antagonist naloxone and K-opioid receptor antagonist nor-binaltorphimine dihydrochloride. Spexin up-regulated the dynorphin and x-opioid receptor gene and protein expression. PCR array assay and real-time PCR analysis show that spexin up-regulated the mRNA level of the FBJ osteosarcoma oncogene (Fos). T-5224, the inhibitor of c FBJ osteosarcoma oncogene (c-Fos)/activator protein 1 (AP-1), blocked the increased mRNA level of Pdyn and Oprkl induced by spexin. I.C.V. spexin (2.43 mg/kg) increased the number of c-Fos positive neurons in most subsections of periaqueductat gray. In addition, in the acetic acid induced writhing test, i.c.v. spexin produced an antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with an antinociceptive effect against acute inflammatory pain.