Authors: Xiaohang Bao Yulong Cai Ying Wang Jinghui Zhao Xie He Dan Yu Jing Huang Sheng Jing Zhiyong Du Tiande Yang Margaret Warner JanAke Gustafsson Xiaotang Fan
Publish Date: 2016/02/05
Volume: 54, Issue: 2, Pages: 1467-1481
Abstract
Increasing evidence indicates that the liver X receptorLXR β modulates inflammatory pain However the molecular mechanisms through which LXRβ modulates pain are unclear Here we found that LXRβnull mice responded more strongly to acute noxious stimuli than wildtype 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 formalinevoked Fos and pERK staining of secondorder 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 formalininjected LXRβ knockout KO mice compared with the WT controls In addition LXRβ deletion in the mice enhanced the formalininduced inflammation with more activated microglia and astrocytes in the spinal cord Furthermore the levels of proinflammatory cytokines IL1β TNFα as well as NFκB in the formalininjected 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 analgesicsThis study was supported by the National Nature Science Foundation of China Nos 31571069 and 81371197 the Natural Science Foundation Project of CQ CSTC 2013jjB10028 the Swedish Research Council and a grant from the Robert A Welch Foundation E0004 JÅG
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