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.

Brain Research
|January 4, 2015
PubMed

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.