The Interaction Between Spinal PDGFRβ and μ Opioid Receptor in the Activation of Microglia in Morphine-Tolerant Rats

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Zheng Li1, Xiaoqian Jia1, Xiaoling Peng1

  • 1Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Journal of Pain Research
|August 9, 2020
PubMed
Abstract

Insights

Morphine tolerance involves spinal platelet-derived growth factor receptor β (PDGFRβ) activation. Repeated morphine use activates PDGFRβ via JNK MAPK, leading to microglia activation and reduced pain relief.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Opioid tolerance limits clinical use of analgesics.
  • Platelet-derived growth factor receptor β (PDGFRβ) plays a role in morphine tolerance.

Purpose of the Study:

  • Investigate spinal PDGFRβ activation mechanisms in morphine tolerance.
  • Elucidate the role of PDGFRβ in opioid-induced microglia activation.

Main Methods:

  • Rats received daily morphine for 7 days, with analgesic effects assessed via tail-flick latency.
  • Western blot and real-time PCR analyzed μ opioid receptor (MOR) and PDGFRβ interactions, microglia activation, and signaling pathways.

Main Results:

  • PDGFRβ activation in the spinal cord induced microglia activation and reduced morphine's analgesic effect.
  • PDGFRβ inhibition suppressed microglia activation during morphine tolerance development.
  • Morphine's μ opioid receptor (MOR) antagonism inhibited PDGFRβ and JNK phosphorylation; JNK inhibition reduced PDGFRβ phosphorylation.

Conclusions:

  • Repeated μ opioid receptor (MOR) activation by morphine induces PDGFRβ transactivation via JNK MAPK in the spinal cord.
  • This PDGFRβ activation leads to microglia activation, contributing to morphine tolerance.
Keywords:
JNK signalingmicrogliamorphine tolerancemu opioid receptorplatelet-derived growth factor receptor β

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