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Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain
Published on: August 8, 2019
NFAT1 Signaling Contributes to Bone Cancer Pain by Regulating IL-18 Expression in Spinal Microglia
Xuetai Chen1, Ying Zeng1, Zizhu Wang2
1Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Department of Anesthesiology, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng, China.
Aims:
This study aimed to test the hypothesis that nuclear factor of activated T cells 1 (NFAT1) signaling contributes to bone cancer pain by regulating interleukin (IL)-18 expression in spinal microglia.
Methods:
This study was performed on male mice using a Lewis lung carcinoma-induced bone cancer pain model. Nociceptive behaviors were evaluated by measuring mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Expression levels were measured via real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence analysis. The effect of pharmacologic intervention of spinal NFAT1/IL-18 signaling on bone cancer pain was the primary outcome.
Results:
NFAT1 expression was upregulated in the spinal microglia after tumor inoculation. Pharmacological inhibition of NFAT1 upregulation prevented and reversed bone cancer-related pain behaviors. In spinal microglia, NFAT1 inhibition decreased p38 MAPK phosphorylation and IL-18 production. Blocking NFAT1 signaling suppressed tumor-induced neuronal sensitization and microglial activation as well as activation of the N-methyl-D-aspartate receptor and the subsequent Ca2+-dependent signaling.
Conclusion:
Microglia NFAT1-p38 signaling contributes to bone cancer pain through IL-18-mediated central sensitization in spinal microglia. NFAT1 could be a potential target for therapeutic intervention to prevent bone cancer pain.
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