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.
Keywords: HIV-1; Pain; Wnt; astrocyte; inflammasome; morphine; neuroinflammation; opioid.