Spinal bromodomain-containing protein 4 contributes to neuropathic pain induced by HIV glycoprotein 120 with morphine in rats

作者: Keiya Takahashi , Hyun Yi , Ching-Hang Liu , Shue Liu , Yuta Kashiwagi

DOI: 10.1097/WNR.0000000000000992

关键词:

摘要: The symptoms of HIV-sensory neuropathy are dominated by neuropathic pain. Recent data show that repeated use opiates enhances the chronic pain states in HIV patients. Limited attention has so far been devoted to exploring exact pathogenesis painful disorder and opiate abuse vivo, for which there is no effective treatment. Bromodomain-containing protein 4 (Brd4) a member bromodomain extraterminal domain (BET) family functions as chromatin 'reader' binds acetylated lysines histones brain neurons mediate transcriptional regulation underlying learning memory. Here, we established model interaction intrathecal envelope glycoprotein 120 (gp120) morphine rats. combination gp120 (gp120/M, 5 days) induced persistent mechanical allodynia compared with either or alone. Mechanical reached lowest values at day 10 from gp120/M application, beginning recover 21. In model, overexpression Brd4 mRNA using RT-qPCR western blots, respectively. Immunohistochemical studies showed was expressed spinal cord dorsal horn. BET inhibitor I-BET762 dose-dependently increased threshold state. present study provides preclinical evidence treating opioids inhibitor.

参考文章(22)
Jianren Mao, Backil Sung, Ru-Rong Ji, Grewo Lim, Neuronal Apoptosis Associated with Morphine Tolerance: Evidence for an Opioid-Induced Neurotoxic Mechanism The Journal of Neuroscience. ,vol. 22, pp. 7650- 7661 ,(2002) , 10.1523/JNEUROSCI.22-17-07650.2002
Su-Bo Yuan, Yuqiang Shi, Jinghong Chen, Xiangfu Zhou, Guangyu Li, Benjamin B. Gelman, Joshua G. Lisinicchia, Susan M. Carlton, Monique R. Ferguson, Alai Tan, Sushil K. Sarna, Shao-Jun Tang, Gp120 in the pathogenesis of human immunodeficiency virus–associated pain Annals of Neurology. ,vol. 75, pp. 837- 850 ,(2014) , 10.1002/ANA.24139
YANGLI SUN, JIE HUANG, KUNPENG SONG, BET protein inhibition mitigates acute myocardial infarction damage in rats via the TLR4/TRAF6/NF-κB pathway. Experimental and Therapeutic Medicine. ,vol. 10, pp. 2319- 2324 ,(2015) , 10.3892/ETM.2015.2789
Xiaohong Chen, Lynn G. Kirby, Jonathan Palma, Khalid Benamar, Ellen B. Geller, Toby K. Eisenstein, Martin W. Adler, The effect of gp120 on morphine's antinociceptive and neurophysiological actions. Brain Behavior and Immunity. ,vol. 25, pp. 1434- 1443 ,(2011) , 10.1016/J.BBI.2011.04.014
Edwige Nicodeme, Kate L. Jeffrey, Uwe Schaefer, Soren Beinke, Scott Dewell, Chun-wa Chung, Rohit Chandwani, Ivan Marazzi, Paul Wilson, Hervé Coste, Julia White, Jorge Kirilovsky, Charles M. Rice, Jose M. Lora, Rab K. Prinjha, Kevin Lee, Alexander Tarakhovsky, Suppression of inflammation by a synthetic histone mimic Nature. ,vol. 468, pp. 1119- 1123 ,(2010) , 10.1038/NATURE09589
Ruturaj R. Masvekar, Nazira El-Hage, Kurt F. Hauser, Pamela E. Knapp, GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity. Molecular and Cellular Neuroscience. ,vol. 65, pp. 11- 20 ,(2015) , 10.1016/J.MCN.2015.01.001
Iain Crawford Anthony, Juan-Carlos Arango, Ben Stephens, Peter Simmonds, Jeanne Elisabeth Bell, The effects of illicit drugs on the HIV infected brain Frontiers in Bioscience. ,vol. 13, pp. 1294- 1307 ,(2008) , 10.2741/2762
Uri Herzberg, Jacqueline Sagen, Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis. Journal of Neuroimmunology. ,vol. 116, pp. 29- 39 ,(2001) , 10.1016/S0165-5728(01)00288-0
Marcus Kaul, Gwenn A. Garden, Stuart A. Lipton, Pathways to neuronal injury and apoptosis in HIV-associated dementia Nature. ,vol. 410, pp. 988- 994 ,(2001) , 10.1038/35073667
Erin D. Milligan, Linda R. Watkins, Pathological and protective roles of glia in chronic pain Nature Reviews Neuroscience. ,vol. 10, pp. 23- 36 ,(2009) , 10.1038/NRN2533