Bone mesenchymal stem cells attenuate radicular pain by inhibiting
microglial activation in a rat noncompressive disk herniation model
Received: 24 October 2017 /Accepted: 8 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses.
Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflamma-
tion and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of
mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was
induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). The study found that the use of NP in
the DRG can induce abnormal mechanical pain, increase the contents of the proinflammatory factors TNF-α and IL-1β, decrease
the content of the anti-inflammatory cytokine TGF-β1 and activate microglia in the spinal dorsal horns (L5) (P < 0.05). BMSC
administration could increase the mechanical withdrawal thresholds dramatically, decrease the contents of IL-1β and TNF-α,
increase the content of TGF-β1 significantly (P < 0.05) and inhibit microglial activation in the bilateral spinal dorsal horn. Our
results indicate that BMSC administration can reduce mechanical allodynia and downregulate the expression of proinflammatory
cytokines by inhibiting microglial activation in the spinal dorsal horn in a rat noncompressive disk herniation model.
Keywords Intervertebral disk herniation
Bone mesenchymal stem cell
Intervertebral disk herniation may cause nerve root injury and
nerve root pain, which mainly manifests as hyperalgesia,
allodynia and conduction velocity reduction (Olmarker et al.
1993). The prominent manifestation of patients with disk
herniation is nerve root pain, which is mainly caused by local
inflammation rather than mechanical disk compression (Zai et
al. 2005). In fact, inflammation caused by the nucleus pulposus
(NP) can directly or indirectly sensitize the nerve roots and
activate microglia in the central nervous system (CNS).
Activated spinal microglia proliferate, undergo morphological
changes and can release nitric oxide, oxygen-free radicals and
proinflammatory factors (Hill-Felberg et al. 1999;Lendahlet
al. 1990; Zai et al. 2005). The release of chemokines from
immune cells and the activation of spinal microglial cells me-
diate nerve root pain (Abbadie 2005; Tsuda et al. 2005; Watkins
and Maier 2003). Increasing evidence has shown that inflam-
matory cytokines, including IL-1, IL-6 and IL-8, TNF-α and
the enzyme cyclooxygenase-2 (COX-2), released by activated
microglia may be critical in the development of nerve root pain
(Casey 2011; Cuellar et al. 2004). However, the function of glia
and inflammatory cytokines in neuropathic pain remains elu-
sive. The inhibition of microglial cell hyperactivation and ex-
cessive inflammatory cytokine release may prove to be a po-
tential effective treatment for radicular pain.
Bone mesenchymal stem cells (BMSCs) are a promis-
ing donor resource for tissue repair and regeneration be-
cause they are multipotent and can differentiate into
Dr. Xiaojian Ye is the main corresponding author of this paper.
Xiaodong Huang, Weiheng Wang and Xilin Liu contributed equally to
Xiaojian Ye and Xiangqun Yang supported this project equally.
* Xiangqun Yang
* Xiaojian Ye
Department of Orthopaedics, Changzheng Hospital, Second Military
Medical University, Shanghai 200003, China
Department of Orthopaedics, Chengdu General Hospital of Chengdu
Military Command Region, Chengdu 610083, China
Department of Anatomy, Institute of Biomedical Engineering,
Second Military Medical University, Shanghai 200433, China
Cell and Tissue Research