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Updated: Oct 6, 2025
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
P2X7 receptor induces microglia polarization to the M1 phenotype in cancer-induced bone pain rat models
Ping Wu1, Guohua Zhou2, Xiaoqi Wu2
1Department of Anesthesiology, 74710The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Background:
The transition from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype presents a novel therapeutic strategy for chronic pain.
Objective:
We investigated the role of microglia polarization in cancer-induced bone pain (CIBP), as well as the role of the P2X7 receptor in modulating M1 to M2 polarization.
Methods:
Walker-256 breast cancer cells were administered into tibias of female rats to induce bone cancer-associated cancer.
Results:
During bone cancer development, the P2X7 receptor and M1 microglia markers were upregulated. In contrast, inhibition of the P2X7 receptor by BBG, a blood-brain barrier-permeable P2X7R-specific antagonist, alleviated the pain and promoted microglia polarization toward the M2 phenotype, while suppressing the M1 phenotype in vivo and in vitro.
Conclusion:
P2X7 receptor-mediated spinal microglia polarization is involved in alleviation of CIBP. Therefore, P2X7R is a potential option for CIBP treatment.
Insights
Targeting the P2X7 receptor shifts microglia from a pro-inflammatory M1 to an anti-inflammatory M2 state, effectively alleviating cancer-induced bone pain (CIBP) and offering a new treatment strategy.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Microglia polarization, shifting from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotypes, is a promising therapeutic target for chronic pain conditions.
- Cancer-induced bone pain (CIBP) is a debilitating condition often associated with complex inflammatory processes in the bone microenvironment.
Purpose of the Study:
- To investigate the role of microglia polarization in the development of CIBP.
- To determine the involvement of the P2X7 receptor in modulating microglia polarization from M1 to M2 phenotypes during CIBP.
Main Methods:
- A rat model of CIBP was established by intra-tibial administration of Walker-256 breast cancer cells.
- The expression of P2X7 receptor and M1 microglia markers was assessed during cancer development.
- The effect of BBG, a P2X7 receptor antagonist, on pain behavior and microglia polarization was evaluated both *in vivo* and *in vitro*.
Main Results:
- Upregulation of P2X7 receptor and M1 microglia markers was observed during CIBP progression.
- Inhibition of the P2X7 receptor using BBG significantly alleviated pain associated with CIBP.
- BBG treatment promoted a shift in microglia polarization towards the M2 phenotype while suppressing the M1 phenotype.
Conclusions:
- Spinal microglia polarization mediated by the P2X7 receptor plays a crucial role in the alleviation of CIBP.
- The P2X7 receptor represents a potential therapeutic target for managing cancer-induced bone pain.
