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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Morphine suppresses peripheral responses and transforms brain myeloid gene expression to favor neuropathogenesis in
Howard S Fox1, Meng Niu2, Brenda M Morsey1
1Departments of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States.
Abstract:
The twin pandemics of opioid abuse and HIV infection can have devastating effects on physiological systems, including on the brain. Our previous work found that morphine increased the viral reservoir in the brains of treated SIV-infected macaques. In this study, we investigated the interaction of morphine and SIV to identify novel host-specific targets using a multimodal approach. We probed systemic parameters and performed single-cell examination of the targets for infection in the brain, microglia and macrophages. Morphine treatment created an immunosuppressive environment, blunting initial responses to infection, which persisted during antiretroviral treatment. Antiretroviral drug concentrations and penetration into the cerebrospinal fluid and brain were unchanged by morphine treatment. Interestingly, the transcriptional signature of both microglia and brain macrophages was transformed to one of a neurodegenerative phenotype. Notably, the expression of osteopontin, a pleiotropic cytokine, was significantly elevated in microglia. This was especially notable in the white matter, which is also dually affected by HIV and opioids. Increased osteopontin expression was linked to numerous HIV neuropathogenic mechanisms, including those that can maintain a viral reservoir. The opioid morphine is detrimental to SIV/HIV infection, especially in the brain.
Insights
Morphine worsens simian immunodeficiency virus (SIV) infection in the brain by creating an immunosuppressive environment and promoting a neurodegenerative phenotype in microglia. This opioid-induced immune suppression is linked to increased viral reservoirs.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Opioid abuse and HIV infection represent twin pandemics with severe physiological impacts, particularly on the brain.
- Previous research indicated morphine increases the viral reservoir in SIV-infected macaques' brains.
Purpose of the Study:
- To investigate the interaction between morphine and SIV to identify host-specific targets.
- To understand how morphine affects the brain during SIV infection.
Main Methods:
- A multimodal approach was used, examining systemic parameters and single-cell analysis of microglia and macrophages in the brain.
- Assessed viral load, immune response, and gene expression profiles.
Main Results:
- Morphine induced an immunosuppressive environment, blunting initial infection responses, which continued despite antiretroviral treatment.
- Antiretroviral drug levels in cerebrospinal fluid and brain tissue remained unaffected by morphine.
- Microglia and brain macrophages exhibited a transcriptional signature associated with neurodegeneration, with significantly elevated osteopontin expression in microglia, particularly in white matter.
Conclusions:
- Morphine is detrimental to SIV/HIV infection, especially within the brain.
- Elevated osteopontin in microglia is linked to HIV neuropathogenesis and viral reservoir maintenance.
- Morphine's immunosuppressive effects and promotion of neurodegeneration exacerbate SIV/HIV brain pathology.
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