Microencapsulation Enhances the Effect of Neural Stem Cells Transplantation on Down-Regulating P2X7 Receptor Over-Expression and Inhibiting Neuropathic Pain

Abstract

Neuropathic pain (NPP) is a common clinical disease symptom, its mechanism is complicated, and there is no good treatment method. Therefore, the exploration of the pathological mechanism and treatment methods of NPP has attracted the attention of many researchers. A large number of studies have shown that P2X7 receptor (P2X7R) plays a key role in the development of NPP. High expression of P2X7R can induce pain. In this study, neural stem cells (NSC) and microencapsulated neural stem cells (MC-NSC) were transplanted into the site of chronic sciatic nerve injury, and behavioral methods were used to detect changes in pain. Expression levels of P2X7R proteins and mRNA were detected by using in situ hybridization, RT-PCR and western-blotting. ELISA method was used to detect the changes of the pro-inflammatory factors IL-6, IL-1β, IL-10 and TNF-a in rat serum. Western-blotting was used to detect p-ERK1/2, p-p38 and ERK1/2 protein expression in dorsal root ganglia (DRG), To explore the effect of NSC and MC-NSC on the treatment of NPP. and compare the difference between the two. The results showed that after chronic constriction injury (CCI), mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats were significantly reduced, the expression levels of P2X7R, p-ERK1/2 and p-p38 in DRG were significantly increased, and IL-6, IL-1β, IL-10 and TNF-a concentrations were significantly increased in serum of rats. After transplantation of NSC and MC-NSC, it was found that expression levels of P2X7R, p-ERK1/2 and p-p38 in DRG were significantly reduced, and IL-6, IL-1β, IL-10 and TNF-a concentrations also significantly decreased in serum, and MWT and TWL of rats increased significantly. Importantly, compared with NSC transplantation, transplantation of MC-NSC could better reduce the expression levels of P2X7R, p-ERK1/2 and p-p38, decrease IL-6, IL-1β, IL-10 and TNF- a concentrations, and inhibit mechanical allodynia in rats. But total ERK1/2 protein expression level remains unchanged. Therefore, our conclusion is that MC-NSC can better reduce the expression level of P2X7R and inhibit NPP, which may become another potential treatment method for treatment of NPP.

Funding Statement: These studies were supported by grants from the National Natural Science Foundation of China (81760418 and 81260190), the Natural Science Foundation of Jiangxi Province (20181BBG70015 and 20181BAB205061).

Declaration of Interests: The authors stated that there is no conflict of interest in this paper.

Ethics Approval Statement: All protocols were approved by the Animal Care and Ethics Committee, China.