Bao Xiaohang, Cai Yulong, Wang Ying, Zhao Jinghui, He Xie, Yu Dan, Huang Jing, Jing Sheng, Du Zhiyong, Yang Tiande, Warner Margaret, Gustafsson Jan-Ake, Fan Xiaotang
Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
Mol Neurobiol. 2017 Mar;54(2):1467-1481. doi: 10.1007/s12035-016-9737-1. Epub 2016 Feb 5.
Increasing evidence indicates that the liver X receptor(LXR) β modulates inflammatory pain. However, the molecular mechanisms through which LXRβ modulates pain are unclear. Here, we found that LXRβ-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 LXRβ knockout (KO) mice compared with the WT controls. In addition, LXRβ 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-1β ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRβ. Taken together, these data indicate that LXRβ is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.
越来越多的证据表明，肝脏X受体（LXR）β可调节炎性疼痛。然而，LXRβ调节疼痛的分子机制尚不清楚。在此，我们发现LXRβ基因敲除小鼠对急性伤害性刺激的反应比野生型（WT）同窝小鼠更强烈（在热板和哈格里夫斯试验中），并且其紧张性炎性疼痛增强（在福尔马林试验中）。这种对炎性疼痛反应性的增加伴随着福尔马林诱发的二级伤害性神经元Fos和pERK染色增强。免疫组织化学显示，与WT对照组相比，福尔马林注射的LXRβ基因敲除（KO）小鼠腰段背角I-II层中降钙素基因相关肽（CGRP）、P物质（SP）和IB4的表达增加。此外，小鼠中LXRβ的缺失增强了福尔马林诱导的炎症，脊髓中有更多活化的小胶质细胞和星形胶质细胞。此外，LXRβ的缺失使福尔马林注射爪中的促炎细胞因子（IL-1β、TNF-α）以及核因子κB（NFκB）水平升高。综上所述，这些数据表明LXRβ参与急性疼痛以及炎性疼痛，因此，它可能被视为开发镇痛药的新靶点。
