HIGHLIGHTS
- •Oligodendrocyte apoptosis decreased myelin proteins in OIH.
- •Oligodendrocyte apoptosis in the PL-mPFC is a key trigger for OIH.
- •Blockage of oligodendrocyte apoptosis in the PL-mPFC prevents OIH.
Abstract
Opioid-induced hyperalgesia (OIH) is a problem associated with prolonged use of opioids
in chronic pain management, and its effective treatment has been hampered by lack
of mechanistic evidence. Oligodendrocytes have recently been linked with several pain-related
diseases; however, little is known its role in OIH. The prelimbic medial prefrontal
cortex (PL-mPFC) has emerged as a significant center of pain regulation, and is rich
in oligodendrocytes. Herein we explored the effect of oligodendrocyte apoptosis of
PL-mPFC on OIH. Using a fentanyl-induced rat model of OIH and proteomics analysis
of the PL-mPFC, we observed a downregulation in 5 types of myelin-related proteins
originating from oligodendrocytes; this was further verified by western blotting.
Meanwhile, cleaved-caspase 3 (an apoptosis marker) was increased, whereas the oligodendrocyte
precursor cell (OPC) marker NG2 remained unchanged. These results suggest that downregulated
myelin-related proteins may be associated with oligodendrocyte apoptosis rather than
a reduction in their generating source, and immunohistochemistry confirmed this hypothesis.
Behaviorally, prophylactic blockade of oligodendrocyte apoptosis by microinjection
of z-DEVD-fmk into the PL-mPFC prevented fentanyl-induced mechanical and thermal hyperalgesia,
but downregulated myelin basic protein (mbp) gradually recovered in 12 h. We suggest
that OIH may be primed in part via oligodendrocyte apoptosis in the PL-mPFC.
Perspective
In this study we showed that oligodendrocyte apoptosis in the PL-mPFC is a key trigger
for fentanyl-induced hyperalgesia. Targeting oligodendrocyte apoptosis in the PL-mPFC
may prevented hyperalgesia priming induced by fentanyl.
Graphical abstract
Graphical Abstract
Key Words
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Article info
Publication history
Published online: January 09, 2022
Accepted:
December 20,
2021
Received in revised form:
December 2,
2021
Received:
July 9,
2021
Footnotes
Funding: This study was supported by grants from the National Natural Science Foundation of China (grants numbers 81974165 and 81771196).
Conflict of interest: There were not any actual or potential conflicts of interest including any financial, personal, or other relationships with other people or organizations.
Identification
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© 2022 by United States Association for the Study of Pain, Inc.
