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Reactive Oxygen Species (ROS) are Critical for Morphine Exacerbation of HIV-1 gp120-Induced Pain

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Abstract

Many HIV patients develop chronic pain and use opioid-derived medicine as primary analgesics. Emerging clinical evidence suggests that chronic use of opioid analgesics paradoxically heightens pain states in patients. This side effect of opioid analgesics has a significant negative impact on clinical practice, but the underlying pathogenic mechanism remains elusive. Using a mouse model of HIV-associated pain, we simulated the development of morphine exacerbation on pain and investigated potential underlying cellular and molecular pathways. We found that repeated morphine treatment promoted astrocyte activation in the spinal dorsal horn (SDH) and up-regulation of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, we observed that morphine administration potentiated mitochondrial reactive oxygen species (ROS) in the SDH of the HIV pain model, especially on astrocytes. Systemic application of the ROS scavenger phenyl-N-t-butyl nitrone (PBN) not only blocked the enhancement of gp120-induced hyperalgesia by morphine but also astrocytic activation and cytokine up-regulation. These findings suggest a critical role of ROS in mediating the exacerbation of gp120-induced pain by morphine.

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Acknowledgements

This work was supported by National Institutes of Health Grants R01NS079166, R01DA036165, R01NS095747 and 1R01DA050530 (SJT) and the Cecil H. and Ida M. Green Distinguished Chair in Neuroscience and Cell Biology (SJT). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Yuqiang Shi, Subo Yuan & Shao-Jun Tang

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YS and SY performed the experiments. YS and SJT wrote the manuscript. SJT designed the study.

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Correspondence to Shao-Jun Tang.

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Shi, Y., Yuan, S. & Tang, SJ. Reactive Oxygen Species (ROS) are Critical for Morphine Exacerbation of HIV-1 gp120-Induced Pain. J Neuroimmune Pharmacol 16, 581–591 (2021). https://doi.org/10.1007/s11481-020-09951-6

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