ArticleCNS neuroscience & therapeutics2026
C/EBPβ Contributes to Cancer-Induced Bone Pain by Inhibiting CD200/CD200R1 in the Spinal Cord.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAdvanced cancer patients still suffer from devastating bone pain, with less efficacious treatments. The spinal microglia activation and neuroinflammation are the pivotal pathological processes of cancer-induced bone pain (CIBP). This study aims to explore whether c/EBPβ negatively regulates CD200R1 to induce microglia-medicated neuroinflammation in the spinal cord of CIBP mice.
methodsThe CIBP mice model was constructed by intrafemoral injection of Lewis lung cancer cells to investigate the role of CD200/CD200R1 signaling and their upstream molecule CCAAT/enhancer binding protein β (c/EBPβ) in CIBP. Mechanical allodynia and thermal hyperalgesia were evaluated by von Frey filaments and hot plate, respectively. Adeno-associated viruses were constructed to regulate the expression of CD200R1 and c/EBPβ. The protein level was assessed by western blotting, and microglia activation was detected by immunofluorescence.
resultsOur results showed that CD200/CD200R1 signaling was inhibited in the spinal cord of CIBP mice. Intrathecal injection of CD200R1 agonist CD200Fc effectively reversed the nociceptive behaviors in CIBP mice. Overexpression of CD200R1 could also effectively ameliorate the pain behaviors and spinal neuroinflammation in CIBP mice. Transcription factor c/EBPβ was upregulated in the spinal cord of CIBP mice. Knockdown of c/EBPβ effectively inhibited the microglia-mediated neuroinflammation by restoring CD200R1 protein levels, alleviating pain behavior in CIBP mice.
conclusionc/EBPβ-mediated suppression of the CD200/CD200R1 signaling pathway represents one potential mechanism in promoting microglial activation and neuroinflammation in the spinal cord of CIBP mice, which provides a potential therapeutic target for CIBP management.
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