Newly Published
Pain Medicine  |   June 2017
Liver X Receptor α Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn
Author Notes
  • From the Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China (J.X., Y.-W.F., W.W., X.-X.Z., X.-H.W., X.-G.L.); Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, People’s Republic of China (X.-H.W., X.-G.L.); and Department of Anesthesiology, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China (L.L.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication July 25, 2016. Accepted for publication April 27, 2017.
    Submitted for publication July 25, 2016. Accepted for publication April 27, 2017.×
  • Research Support: Supported by grants from the National Natural Science Foundation (Beijing, People’s Republic of China, Nos. U1201223, 81200856, and 81471250); Fundamental Research Funds for the Central Universities (Beijing, People’s Republic of China, No. 13ykpy05); Nature Science Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China, No. 2014A030313029); Scientific Research Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China, No. 2016A020215035); and by scholarships from the Chinese Scholarship Council (Beijing, People’s Republic of China). All grants were awarded to Dr. Wei except No. U1201223 which was awarded to Dr. Liu.
    Research Support: Supported by grants from the National Natural Science Foundation (Beijing, People’s Republic of China, Nos. U1201223, 81200856, and 81471250); Fundamental Research Funds for the Central Universities (Beijing, People’s Republic of China, No. 13ykpy05); Nature Science Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China, No. 2014A030313029); Scientific Research Foundation of Guangdong Province of China (Guangzhou, People’s Republic of China, No. 2016A020215035); and by scholarships from the Chinese Scholarship Council (Beijing, People’s Republic of China). All grants were awarded to Dr. Wei except No. U1201223 which was awarded to Dr. Liu.×
  • Competing Interests: The authors declare that they have no competing interests.
    Competing Interests: The authors declare that they have no competing interests.×
  • Correspondence: Address correspondence to Dr. Wei: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, China. weixhong@mail.sysu.edu.cn.Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Central and Peripheral Nervous Systems / Pain Medicine
Pain Medicine   |   June 2017
Liver X Receptor α Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn
Anesthesiology Newly Published on June 15, 2017. doi:10.1097/ALN.0000000000001718
Anesthesiology Newly Published on June 15, 2017. doi:10.1097/ALN.0000000000001718
Abstract

Background: Liver X receptors, including α and β isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown.

Methods: A spared nerve injury model was established in adult male rats and mice. Von Frey tests were performed to evaluate the neuropathic pain behavior; Western blot and immunohistochemistry were performed to understand the underlying mechanisms.

Results: Intrathecal injection of a specific liver X receptor agonist T0901317 or GW3965 could either prevent the development of mechanical allodynia or alleviate the established mechanical allodynia, both in rats and wild-type mice. GW3965 could inhibit the activation of glial cells and the expression of tumor necrosis factor-α (mean ± SD: 196 ± 48 vs. 119 ± 57; n = 6; P < 0.01) and interleukin 1β (mean ± SD: 215 ± 69 vs. 158 ± 74; n = 6; P < 0.01) and increase the expression of interleukin 10 in the spinal dorsal horn. All of the above effects of GW3965 could be abolished by liver X receptor α mutation. Moreover, more glial cells were activated, and more interleukin 1β was released in the spinal dorsal horn in liver X receptor α knockout mice than in wild-type mice after spared nerve injury. Aminoglutethimide, a neurosteroid synthesis inhibitor, blocked the inhibitory effect of T0901317 on mechanical allodynia, on the activation of glial cells, and on the expression of cytokines.

Conclusions: Activation of liver X receptor α inhibits mechanical allodynia by inhibiting the activation of glial cells and rebalancing cytokines in the spinal dorsal horn via neurosteroids.