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MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain
Di Jin1, Jian-Ping Yang1, Ji-Hua Hu1
1Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Abstract:
Accumulating evidence suggests that chemokine monocyte chemoattractant protein-1 (MCP-1) is significantly involved in the activation of spinal microglia associated with pathological pain, at the same time that the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) pathway localized in spinal microglia is involved in both neuropathic and inflammatory pain. However, whether there is a connection between MCP-1 and the PI3K/Akt pathway and in their underlying mechanisms in bone cancer pain (BCP) has not yet been elucidated. In the current study, we investigated the expression changes of p-Akt in microglia and OX-42 (microglia marker) after being stimulated with MCP-1 in vitro, as well as in a BCP model that was established by an intramedullary injection of mammary gland carcinoma cells(Walker 256 cells) into the tibia of rats. We observed a significant increase in expression levels of p-Akt and OX-42 in microglia as well as in spinal dorsal horns of BCP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody or PI3K inhibitor LY294002 reduced the expression of p-Akt or OX-42, and LY294002 attenuated the mechanical allodynia of BCP rats. These results suggest that MCP-1 may stimulate spinal microglia via the PI3K/Akt pathway in BCP.
Insights
Monocyte chemoattractant protein-1 (MCP-1) activates spinal microglia through the PI3K/Akt pathway, contributing to bone cancer pain (BCP). Inhibiting MCP-1 or PI3K/Akt reduces pain signaling in BCP models.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Monocyte chemoattractant protein-1 (MCP-1) is implicated in pathological pain via spinal microglia activation.
- The phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) pathway in spinal microglia is involved in neuropathic and inflammatory pain.
- The precise mechanisms linking MCP-1 and the PI3K/Akt pathway in bone cancer pain (BCP) remain unclear.
Purpose of the Study:
- To investigate the relationship between MCP-1 and the PI3K/Akt pathway in spinal microglia within a BCP model.
- To elucidate the underlying molecular mechanisms of MCP-1 and PI3K/Akt pathway involvement in BCP.
Main Methods:
- In vitro stimulation of microglia with MCP-1 to assess p-Akt and OX-42 expression.
- Establishment of a rat BCP model via intramedullary injection of Walker 256 mammary carcinoma cells into the tibia.
- Intrathecal administration of anti-MCP-1 neutralizing antibody or PI3K inhibitor LY294002 in BCP rats.
Main Results:
- BCP rats exhibited significantly increased expression of p-Akt and OX-42 in spinal microglia and dorsal horns.
- Anti-MCP-1 antibody or LY294002 treatment reduced p-Akt and OX-42 expression in BCP rats.
- LY294002 administration attenuated mechanical allodynia in BCP rats.
Conclusions:
- MCP-1 may activate spinal microglia in BCP by stimulating the PI3K/Akt pathway.
- Targeting the MCP-1/PI3K/Akt signaling axis presents a potential therapeutic strategy for BCP-induced pain.
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