Open AccessReactive Oxygen Species (ROS) are Critical for Morphine Exacerbation of HIV-1 gp120-Induced Pain
Author(s) -
Yuqiang Shi,
Subo Yuan,
Shuang Tang
Publication year - 2020
Publication title -
journal of neuroimmune pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.219
H-Index - 70
eISSN - 1557-1904
pISSN - 1557-1890
DOI - 10.1007/s11481-020-09951-6
Subject(s) - morphine , exacerbation , opioid , hyperalgesia , reactive oxygen species , microglia , medicine , pharmacology , chronic pain , nociception , anesthesia , inflammation , chemistry , immunology , receptor , biochemistry , psychiatry
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. Graphical abstract.