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pISSN 2005-9159
eISSN 2093-0569

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Korean J Pain

Published online March 11, 2025

Copyright © The Korean Pain Society.

Bone marrow mesenchymal stem cells improve bone cancer pain by inhibiting p38MAPK phosphorylation and microglia activation

Houming Kan1,2,3 , Jinzhao Huang1,2,3 , Xiaodie Gui1,2,3 , Wendi Tian1,2,3 , Lijun Fan4 , Xuetai Chen1,2,3 , Xiaotong Ding5 , Liping Chen6 , Wen Shen6

1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
2Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China
3NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, China
4Department of Anesthesiology, Affiliated Hospital of Soochow University, Suzhou, China
5School of Nursing, Peking Union Medical College, Beijing, China
6Department of Pain, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

Correspondence to:Wen Shen
Department of Pain, Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou 221002, China
Tel: +86 0516-85807917, Fax: +86 0516-85802018, E-mail: shenwenxmu@163.com

Received: November 25, 2024; Revised: January 12, 2025; Accepted: January 13, 2025

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

Keywords: Bone Neoplasms, Cancer Pain, Hyperalgesia, Mesenchymal Stem Cells, Microglia, Mitogen-Activated Protein Kinase Kinases, Receptors, CXCR4, Spinal Cord Dorsal Horn.