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Inhibition of neuropathic hyperalgesia by intrathecal bone marrow stromal cells is associated with alteration of multiple soluble factors in cerebrospinal fluid

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Abstract

Injury-induced neuropathic pain remains a serious clinical problem. Recent studies indicate that bone marrow stromal cells (BMSCs) effectively attenuate chronic neuropathic pain in animal models. Here, we examined the therapeutic effect of intrathecal administration of BMSCs isolated from young (1-month-old) rats on pain hypersensitivity induced by tibial nerve injury. Cerebrospinal fluid (CSF) was collected and analyzed to examine the effect of BMSC administration on the expression of 67 soluble factors in CSF. A sustained remission in injury-induced mechanical hyperalgesia was observed in BMSC-treated rats but not in control animals. Engrafted BMSCs were observed in spinal cords and dorsal root ganglia at 5 weeks after cell injection. Injury significantly decreased the levels of six soluble factors in CSF: intercellular adhesion molecule 1 (ICAM-1), interleukin-1β (IL-1β), IL-10, hepatocyte growth factor (HGF), Nope protein, and neurogenic locus notch homolog protein 1 (Notch-1). Intrathecal BMSCs significantly attenuated the injury-induced reduction of ICAM-1, IL-1β, HGF, IL-10, and Nope. This study adds to evidence supporting the use of intrathecal BMSCs in pain control and shows that this effect is accompanied by the reversal of injury-induced reduction of multiple CSF soluble factors. Our findings suggest that these soluble factors may be potential targets for treating chronic pain.

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Acknowledgements

This work was supported by grant from the National Institute of Neurological Disorders and Stroke (R01NS079626-01) to QHH. Authors thank Zhen Liu for assistance in histological sample preparation.

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Authors and Affiliations

  1. Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Gregory Fischer, Fei Wang, Hongfei Xiang, Xiaowen Bai, Hongwei Yu & Quinn H. Hogan

  2. Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi, People’s Republic of China

    Fei Wang

  3. Department of Orthopedic Surgery, Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China

    Hongfei Xiang

  4. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, 53295, USA

    Hongwei Yu & Quinn H. Hogan

Authors
  1. Gregory Fischer
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  2. Fei Wang
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  3. Hongfei Xiang
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  4. Xiaowen Bai
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  5. Hongwei Yu
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  6. Quinn H. Hogan
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Contributions

HY and QHH contributed to conception and design of the study; GF, HY, and QHH helped in performing experiments, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; FW and HX performed experiments and data analysis; XB helped with consultant.

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Correspondence to Hongwei Yu or Quinn H. Hogan.

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The authors indicated no potential conflicts of interest.

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221_2017_5000_MOESM1_ESM.xlsx

Supplementary Table 1. Complete results of antibody array. Mean concentration of each soluble factor in CSF (n = 5 for each group) with SEM. (XLSX 13 kb)

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Fischer, G., Wang, F., Xiang, H. et al. Inhibition of neuropathic hyperalgesia by intrathecal bone marrow stromal cells is associated with alteration of multiple soluble factors in cerebrospinal fluid. Exp Brain Res 235, 2627–2638 (2017). https://doi.org/10.1007/s00221-017-5000-x

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  • DOI: https://doi.org/10.1007/s00221-017-5000-x

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