Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain
Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain
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肝脏 X 受体 β 参与福尔马林引起的自发性疼痛
DOI：
10.1007/s12035-016-9737-1
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发表时间：
2017-03-01
影响因子：
5.1
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
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作者：
Bao, Xiaohang;Cai, Yulong;Fan, Xiaotang
越来越多的证据表明，肝脏X受体(LXR) β调节炎症性疼痛。然而，LXR β调节疼痛的分子机制尚不清楚。在这里，我们发现LXR β缺失小鼠对急性有害刺激的反应比野生型（WT）同伴更强烈（在热板和哈格里夫斯测试中），并且在福尔马林测试中有增强的强直性炎症疼痛。这种对炎症性疼痛的反应性增加伴随着福尔马林引起的二级伤害神经元Fos和pERK染色的增强。免疫组化结果显示，与WT对照组相比，注射福尔马林LXR β敲除（KO）小鼠腰背角I-II层CGRP、SP和IB4的表达增加。此外，小鼠LXR β缺失增强了福尔马林诱导的炎症，脊髓中的小胶质细胞和星形胶质细胞被激活。此外，由于LXR β的缺失，注射福尔马林的爪中促炎细胞因子（IL-1 β, tnf - α）和NF κ B的水平升高。综上所述，这些数据表明LXR β参与急性和炎症性疼痛，因此，它可能被认为是开发镇痛药的新靶点。
Increasing evidence indicates that the liver X receptor(LXR) beta modulates inflammatory pain. However, the molecular mechanisms through which LXR beta modulates pain are unclear. Here, we found that LXR beta-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXR beta knockout (KO) mice compared with the WT controls. In addition, LXR beta deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1 beta ,TNF-alpha) as well as NF kappa B in the formalin-injected paw were elevated by the loss of LXR beta. Taken together, these data indicate that LXR beta is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.