Morphine and HIV-1 gp120 cooperatively promote pathogenesis in the spinal pain neural circuit

Yuqiang Shi, Subo Yuan, Shao-Jun Tang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalMolecular pain
Volume15
DOIs
StatePublished - Jul 1 2019

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Keywords

  • astrocyte
  • HIV-1
  • inflammasome
  • morphine
  • neuroinflammation
  • opioid
  • Pain
  • Wnt

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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