@article{caae3ea3b7cf446a9a6c73da39fa1ec1,
title = "Morphine and HIV-1 gp120 cooperatively promote pathogenesis in the spinal pain neural circuit",
abstract = "Opioids are common analgesics for pain relief in HIV patients. Ironically, emerging clinical data indicate that repeated use of opioid analgesics in fact leads to a heightened chronic pain state. To understand the underlying pathogenic mechanism, we generated a mouse model to study the interactive effect of morphine and HIV-1 gp120 on pain pathogenesis. We simulated chronic pain in the model by showing that repeated morphine administrations potentiated HIV-1 intrathecal gp120-induced pain. Several spinal cellular and molecular pathologies that are implicated in the development of HIV-associated pain are exacerbated by morphine, including astroglial activation, pro-inflammatory cytokine expression and Wnt5a signaling. We further demonstrated that inhibition of Wnt5a not only reversed the glial activation and cytokine upregulation but also the exacerbation of gp120-induced pain. These studies establish a mouse model for the opioid exacerbation of HIV-associated pain and reveal potential cellular and molecular mechanisms by which morphine enhances the pain.",
keywords = "HIV-1, Pain, Wnt, astrocyte, inflammasome, morphine, neuroinflammation, opioid",
author = "Yuqiang Shi and Subo Yuan and Tang, {Shao Jun}",
note = "Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Institutes of Health Grants R01NS079166, R01DA036165, and R01NS095747 (to SJT) The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Recombinant HIV-1Balenvelope glycoprotein gp120 (Cat # 4961) was obtained through the National Institutes of Health (NIH) AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH. Antibodies used for immunoblotting and/or immunostaining included glial fibrillary acidic protein (GFAP; 1:5000, 04–1062 for immunoblotting; 1:500, MAB360 for immunostaining; Millipore), Iba1 (1:1000, ab178847, Abcam), CD11b (1:1000, ab13357, Abcam), Wnt5a (1:1000, 2530, Cell Signaling Technology), Wnt3a (1:1000, MAB1324, R&D), phosphorylated c-Jun N-terminal kinase (p-JNK; 1:1000, 9251, Cell Signaling Technology), caspase 1 (1:1000 for immunoblotting, 1:200 for immunostaining, 06–503, Millipore), interleukin (IL)-1β (1:500, ab1413-I, Millipore), tumor necrosis factor (TNF)-α (1:500, ab2148P, Millipore), and β-actin (1:1000, sc-1616-R, Santa Cruz Biotechnology). Publisher Copyright: {\textcopyright} The Author(s) 2019.",
year = "2019",
month = jul,
day = "1",
doi = "10.1177/1744806919868380",
language = "English (US)",
volume = "15",
journal = "Molecular Pain",
issn = "1744-8069",
publisher = "BioMed Central",
}