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 language | English (US) |
|---|---|
| Journal | Molecular pain |
| Volume | 15 |
| DOIs | |
| State | Published - 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
Cite this
Morphine and HIV-1 gp120 cooperatively promote pathogenesis in the spinal pain neural circuit. / Shi, Yuqiang; Yuan, Subo; Tang, Shao-Jun.
In: Molecular pain, Vol. 15, 01.07.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Morphine and HIV-1 gp120 cooperatively promote pathogenesis in the spinal pain neural circuit
AU - Shi, Yuqiang
AU - Yuan, Subo
AU - Tang, Shao-Jun
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - astrocyte
KW - HIV-1
KW - inflammasome
KW - morphine
KW - neuroinflammation
KW - opioid
KW - Pain
KW - Wnt
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U2 - 10.1177/1744806919868380
DO - 10.1177/1744806919868380
M3 - Article
VL - 15
JO - Molecular Pain
JF - Molecular Pain
SN - 1744-8069
ER -