Temple Awarded 5-year, $3.27 Million NIH Grant to Investigate Inflammation Associated with HIV Infection in the Context of Opioid Addiction
Research will focus on why HIV infection in the brain leads to greater sensitivity to pain and reduced effectiveness of opioid therapeutics
The National Institutes of Health has awarded a Temple research team a 5-year, $3.27 million grant to study neuroinflammation following HIV-infection in the context of opioid addiction. Yuri Persidsky, MD, PhD, Chair and Professor of Pathology and Laboratory Medicine at the Lewis Katz School of Medicine at Temple University (LKSOM) and Thomas Rogers, PhD, Director of the Center for Inflammation, Translational and Clinical Lung Research, Professor of Pharmacology and Professor in the Fels Institute for Cancer Research and Molecular Biology at LKSOM, are co-principal investigators on the grant.
“Results of this funded study will have broad implications for understanding how chronic inflammation and over-production of certain inflammatory molecules leads to diminished efficacy of opioids, resulting in drug addiction,” said Dr. Persidsky.
Opioid drug abuse is a critical contributor to the global AIDS epidemic. HIV-associated neuropathy remains a clinically significant issue for patients infected with HIV, even in the current era of anti-retroviral therapy. Neuropathy occurs whenever cells are damaged or destroyed, which affects the normal activity of the nerves of the nervous system and can lead to many symptoms including severe pain. HIV-infected opioid abusers demonstrate a more severe neuropathy than non-opioid abusers. The reasons for this greater neuropathy remain uncertain and will be investigated by Drs. Persidsky and Rogers and their teams.
Current evidence suggests that neuroinflammation following HIV-infection is associated with the production of pro-inflammatory cytokines and chemokines, and plays a significant role in the development of HIV-associated neuropathic pain. Cytokines are signaling molecules secreted by certain cells of the immune system. Cytokines mediate and regulate immunity, inflammation and the production of blood cells. Chemokines are a type of cytokine that direct white blood cells to infected or damaged tissues. Neurons in the brain contain various receptors, including chemokine and opioid receptors, which receive signals from nearby cells.
The mechanism by which these chemokines might promote neuropathic pain is not currently understood. However, Drs. Rogers and Persidsky have previously reported that chemokine receptor activation, as a result of chemokine production in the brain, leads to the cross-desensitization of opioid receptors. This leads to greater sensitivity to pain, and a decrease in the efficacy of opioid therapeutics.
“We propose that HIV infection in the brain results in an inflammatory response, which promotes the production of inflammatory chemokines, leading to the activation of the respective chemokine receptors, which finally results in the cross-desensitization of opioid receptors,” said Dr. Rogers. “The consequence of this set of events is an elevated sensitivity to pain stimuli.”
This new NIH-funded research will test these processes using mouse models to evaluate the influence of HIV gp120 in the induction of neuroinflammation, including the associated neuropathic pain. HIV gp120 is a molecule that is part of the outer layer of the virus and facilitates HIV entry into the host cell. The research will also attempt to address the ability of morphine to reduce the development of the neuropathic pain response. Researchers also hope to confirm these studies by analyzing HIV infection using a humanized mouse model.
“We believe the results from these studies will greatly enhance our understanding of the mechanisms which contribute to the development of neuroinflammation in HIV-infected subjects, including those who are opiate abusers,” added Dr. Rogers.
“These studies should provide novel information that explains the relationship between HIV-induced neuroinflammation and short and long-term exposure to opioid drugs of abuse, as well as issues related to the development of HIV-induced neuropathic pain,” said Dr. Persidsky.
Editor’s Note: The research detailed in this release was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA049745. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.