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Morphine promotes microglial activation by upregulating the EGFR/ERK signaling pathway
Yaqiong Yang1, Yu Sun1, Rong Hu1
1Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, PR China.
Plos One
|September 14, 2021
Summary
Morphine tolerance involves microglial activation, which can be suppressed by targeting the epidermal growth factor receptor (EGFR)/ERK signaling pathway. This pathway
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Opioids like morphine are vital analgesics but efficacy is limited by tolerance and side effects.
- Microglial activation and pro-inflammatory cytokine production are implicated in morphine tolerance, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of epidermal growth factor receptor (EGFR) in morphine-induced microglial activation.
- To explore the EGFR/ERK signaling pathway as a potential target for mitigating morphine tolerance.
Main Methods:
- Utilized mouse microglial BV-2 cells stimulated with morphine or treated with EGFR inhibitor AG1478.
- Assessed microglial activation markers (CD11b), EGFR/ERK signaling, cell migration, and cytokine production (IL-1β, TNF-α).
Main Results:
- Morphine increased CD11b expression, EGFR/ERK phosphorylation, BV-2 cell migration, and IL-1β/TNF-α production in a dose- and time-dependent manner.
- Inhibition of EGFR signaling with AG1478 attenuated morphine-induced microglial activation, migration, and cytokine release.
Conclusions:
- The EGFR/ERK signaling pathway plays a critical role in morphine-induced microglial activation.
- Targeting the EGFR/ERK pathway offers a potential therapeutic strategy to suppress morphine tolerance by reducing microglial activation.
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