FMRP acts as a key messenger for visceral pain modulation.
FMRP acts as a key messenger for visceral pain modulation.
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FMRP 是内脏疼痛调节的关键信使
DOI：
10.1177/1744806920972241
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发表时间：
2020-01
期刊：
影响因子：
3.3
通讯作者：
Liu SB
中科院分区：
文献类型：
--
作者：
Yang LK;Lu L;Feng B;Wang XS;Yue J;Li XB;Zhuo M;Liu SB
内脏疼痛是一种常见的临床症状，是由机械牵拉、痉挛、缺血和炎症引起的。脆性X综合征（FXS）是一种遗传性疾病，缺乏脆性X智力低下蛋白（FMRP），其特征是中度或重度智力和发育障碍。以往的研究报道，FXS患者有自我伤害行为，这可能与伤害性敏化缺陷有关。然而，FMRP在内脏痛中的作用仍不清楚。本研究以FMR 1基因敲除小鼠和SH-SY 5 Y细胞为研究对象，探讨FMRP在内脏痛调节中的作用。数据显示，FMR 1 KO小鼠对酵母聚糖治疗不敏感。在前扣带皮层（ACC），一个参与疼痛过程的结构，记录显示较少的突触前谷氨酸释放和突触后反应的FMR 1基因敲除小鼠相比，野生型（WT）小鼠注射酵母多糖后。酵母多糖处理引起ACC中腺苷酸环化酶1（AC 1）（一种疼痛相关酶）和NMDA GluN 2B受体的增强。最后，我们发现酵母多糖处理可导致ACC中FMRP的表达增加，这一结果在体外培养的SH-SY 5 Y细胞中得到进一步证实。我们的研究结果表明，FMRP是必需的NMDA GluN 2B和AC 1上调，和GluN 2B/AC 1/FMRP形成一个正反馈回路，以调节内脏痛。
Visceral pain is a common clinical symptom, which is caused by mechanical stretch, spasm, ischemia and inflammation. Fragile X syndrome (FXS) with lack of fragile X mental retardation protein (FMRP) protein is an inherited disorder that is characterized by moderate or severe intellectual and developmental disabilities. Previous studies reported that FXS patients have self-injurious behavior, which may be associated with deficits in nociceptive sensitization. However, the role of FMRP in visceral pain is still unclear. In this study, the FMR1 knock out (KO) mice and SH-SY5Y cell line were employed to demonstrate the role of FMRP in the regulation of visceral pain. The data showed that FMR1 KO mice were insensitive to zymosan treatment. Recording in the anterior cingulate cortex (ACC), a structure involved in pain process, showed less presynaptic glutamate release and postsynaptic responses in the FMR1 KO mice as compared to the wild type (WT) mice after zymosan injection. Zymosan treatment caused enhancements of adenylyl cyclase 1 (AC1), a pain-related enzyme, and NMDA GluN2B receptor in the ACC. However, these up-regulations were attenuated in the ACC of FMR1 KO mice. Last, we found that zymosan treatment led to increase of FMRP levels in the ACC. These results were further confirmed in SH-SY5Y cells in vitro. Our findings demonstrate that FMRP is required for NMDA GluN2B and AC1 upregulation, and GluN2B/AC1/FMRP forms a positive feedback loop to modulate visceral pain.
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