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Updated: Feb 8, 2026
08:26
Simultaneous Imaging of Microglial Dynamics and Neuronal Activity in Awake Mice
Published on: August 23, 2022
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Neuronal complement cascade drives bone cancer pain via C3R mediated microglial activation
Xiaoxia Huang1, Jinyuan Li2, Jin Xie3
1Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan City 442000, Hubei Province, China.
Brain Research
|June 18, 2018
Summary
The neuronal complement pathway, involving C1, C2, and C3, drives spinal cord microglia activation, contributing to bone cancer pain (BCP). Inhibiting this pathway alleviates pain, offering a potential therapeutic target for BCP.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Spinal cord microglia activation is critical for bone cancer pain (BCP).
- The communication pathway linking neuronal activity and microglial activation in BCP remains unclear.
- The role of the complement system in BCP pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of the neuronal complement cascade in the development of bone cancer pain.
- To identify the specific components of the complement pathway involved in microglial activation.
- To explore therapeutic strategies targeting the complement system for BCP relief.
Main Methods:
- Induction of BCP in rats via tibial carcinoma implantation.
- RNAi-lentivirus-mediated knockdown of complement components (C1, C2, C3) in the spinal cord.
- Intrathecal administration of minocycline (microglial inhibitor) and compstatin (C3 inhibitor).
- In vitro experiments assessing microglial proliferation in response to complement activation products.
Main Results:
- C1, C2, and C3 were found in neurons and increased with BCP, correlating with microglial activation.
- Knockdown of C1, C2, or C3 significantly inhibited microglial activation and prevented BCP development.
- Minocycline and compstatin treatments reversed BCP, confirming the roles of microglia and complement.
- Neuronal complement activation, specifically via C3 and its receptor (C3R), promotes microglial activation.
- In vitro, C3 activation product (iC3b) enhanced microglial proliferation, while compstatin inhibited it.
Conclusions:
- The neuronal complement pathway, involving C1, C2, and C3, is a key mediator of spinal cord microglia activation in BCP.
- Targeting the complement pathway, particularly C3 and its receptor, offers a promising therapeutic avenue for managing bone cancer pain.
- Understanding the C3R-mediated signaling provides critical insights into the neuro-immune interactions driving cancer pain.
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