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Published on: January 7, 2019
Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia
Houming Kan1,2,3, Jinzhao Huang1,2,3, Xiaodie Gui1,2,3
1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
Background:
Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.
Methods:
We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.
Results:
Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice's mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.
Conclusions:
Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.
Insights
Bone marrow mesenchymal stem cells (BMSCs) offer temporary pain relief for bone cancer pain (BCP) in mice. This analgesic effect is linked to reduced spinal microglia and p-p38 MAPK activation, suggesting a novel therapeutic avenue.
Area of Science:
- Oncology
- Stem Cell Biology
- Pain Management
Background:
- Bone cancer pain (BCP) presents significant challenges in current treatment paradigms.
- Bone marrow mesenchymal stem cells (BMSCs) show promise for BCP management, but underlying mechanisms require elucidation.
Purpose of the Study:
- To investigate the efficacy and mechanisms of BMSCs in alleviating bone cancer pain.
- To establish a mouse model for studying BCP and BMSC therapeutic potential.
Main Methods:
- Generation of a mouse model for BCP using Lewis lung carcinoma cells.
- Assessment of BMSC analgesic effects via behavioral tests, X-ray, histology, western blotting, and immunofluorescence.
- Analysis of spinal cord changes, including neuronal activity and inflammatory markers.
Main Results:
- BMSCs administered intrathecally temporarily reduced mechanical and thermal hyperalgesia in BCP mice.
- BMSC treatment did not impair motor function.
- Observed effects correlated with the inhibition of spinal microglia and p-p38 MAPK activation, potentially involving CXCR4-mediated homing.
Conclusions:
- Intrathecal BMSCs provide temporary analgesia for BCP in mice.
- The mechanism involves inhibiting p-p38 protein expression and microglia activation.
- BMSCs represent a potential therapeutic strategy for bone cancer pain.
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