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Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain

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Abstract

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.

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Acknowledgments

This 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 (E-0004, J-ÅG).

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Authors and Affiliations

  1. Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Xiaohang Bao, Dan Yu, Jing Huang, Sheng Jing, Zhiyong Du & Tiande Yang

  2. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China

    Xiaohang Bao, Yulong Cai, Ying Wang, Jinghui Zhao, Xie He & Xiaotang Fan

  3. Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, 77054, USA

    Margaret Warner & Jan-Ake Gustafsson

  4. Department of Biosciences and Nutrition, Karolinska Institute, Novum, Novum, 141 86, Sweden

    Jan-Ake Gustafsson

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  1. Xiaohang Bao
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  2. Yulong Cai
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  3. Ying Wang
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Correspondence to Tiande Yang, Jan-Ake Gustafsson or Xiaotang Fan.

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Bao, X., Cai, Y., Wang, Y. et al. Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain. Mol Neurobiol 54, 1467–1481 (2017). https://doi.org/10.1007/s12035-016-9737-1

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