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

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.