Stem Cells in the Treatment of Neuropathic Pain: Research Progress of Mechanism

Table 3

Preclinical study of stem cells involved in spinal mechanism in the treatment of neuropathic pain.

Cell type (source)	Delivery site	Cell number	Model of NP and species	Brief spinal mechanism	Author and year
BMSC (rats)	i.v.		SNL (rats)	Inhibited the phosphorylation of GluN2A in RVM, reduced the expression of PKCG, inhibited the expression of NMDA receptors, thus resisting the development of central sensitization.	Guo et al. [56]
BMSCs (mice)	i.t.		CCI (mice)	Released TGF-β, regulated the excitatory synaptic transmission of spinal cord neurons, and reduced the increase in neuronal excitability after nerve injury, thus resisting the development of central sensitization.	Chen et al. [38]
BMSCs (rats)	i.v.		CCI (rats)	Decreased the increase of GFAP expression in rat spinal cord induced by CCI, reduced the expression of TGF-α, and reduced the apoptosis of tissue cells.	Forouzanfar et al. [60]
BMSCs (rats)	i.t.		Noncompressive disk herniation (rats)	Decreased the mRNA and protein expression of TNF-α and IL-1β, upregulated the expression of TGF-β, and reduced the activation of microglia in the dorsal horn of the spinal cord.	Huang et al. [61]
BMSCs (human)	i.t.		SCI (rats)	Reduced the activation of spinal microglia, apoptosis, and autophagy of spinal cord cells.	Romero-Ramirez et al. [62]
BMSCs (mice)	Direct implantation of the injured site		SCI (mice)	Decreased the activation of p-p38MAPK and pERK1/2 in microglia induced by SCI, and the expression of CREB and PKC-c in injured and surrounding dorsal horn neurons.	Watanabe et al. [64]
IL-1β-BMSCs (rats)	i.t.		SNL (rats)	Decreased the activation of astrocytes in the spinal cord and reduced the expression level of CCL7 in the spinal cord, thus inhibiting the activation of microglia.	Li et al. [65]
BMSCs (rats)	i.t.		CCD (rats)	Inhibited the expression of P2X4R in spinal microglia but did not affect the activation of microglia induced by CCD.	Teng et al. [66]
ADSCs (autologous, rats)	s.c.		Burn-induced neuropathic pain (rats)	Reduced the expression of astrocytes in the spinal cord and reduced the apoptosis and autophagy of spinal cord cells.	Lin et al. [67]
ADSCs (human)	Direct implantation of the injured site		SCI (rats)	Reduced the syringomyelia caused by SCI and increased the number of axons around the cavity.	Sarveazad et al. [42]

Notes: the above-mentioned experimental studies have shown that the stem cells used in the study are effective and analgesic in the treatment of neuropathic pain in this model. Abbreviations: SNL: spinal cord nerve ligation model; CCI: chronic constriction nerve injury model; SCI: spinal cord injury model; CCD: chronic compression of the dorsal root ganglion model; BMSCs: bone marrow mesenchymal stem cells; IL-1β-BMSCs: interleukin-1β pretreated bone marrow stromal cells; ADSCs: adipose-derived stem cells; i.v.: intraperitoneal injection; i.t.: intrathecal injection; s.c.: subcutaneous injection.