Effects And Mechanisms Of Bone Marrow Mesenchymal Stem Cell Transplantation In Treatment Of Complex Regional Pain Syndrome Type Ⅰ

ObjectiveComplex regional pain syndrome(CRPS)is a severe chronic pain disease.There is no specific treatment for CRPS.Bone marrow mesenchymal stem cells(BMSCs)have potential for multidirectional differentiation.BMSCs transplantation has achieved positive results in the treatment of neurological diseases.The main aim of the study is to investigate the effects of bone marrow mesenchymal stem cell transplantation in treatment of complex regional pain syndrome type I,and its mechanismsMethods(1)Bone marrow isolated from SD rats was purified and cultured to obtain the BMSCs using the whole bone marrow adherence method.(2)CRPS-I rat model was established.The SD rats were randomly divided into 4 groups(15 in each group),blank group(rats without any intervention),experimental group(CRPS-I rat model without any intervention),treatment group(CRPS-I rat model with intrathecal BMSCs transplantation)and control group(rats with intrathecal cell culture fluid injection).Thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWL)were used to determine the pain threshold.(3)The expression intensity of Brain derived neurotrophic factor(BDNF)in Dorsal root ganglion(DRG)before and after the intervention was examined by immunofluorescence staining.(4)The mRNA expression of BDNF、CGRP、SP、TNF-α and IL-6 in rat dorsal root ganglia,and the expression of voltage-gated sodium channel subtypes Nav1.7,Nav1.8,and Nav1.9 at mRNA and protein levels were measured by reverse transcription polymerase chain reaction(RT-PCR)and Western blot analysis.(5)The protein expression of BDNF、CGRP、SP、TNF-α and IL-6 in rat dorsal root ganglia,and the expression of voltage-gated sodium channel subtypes Nav1.7,Nav1.8,and Nav1.9 at mRNA and protein levels were measured by Western blot analysis.Results(1)BMSCs were confirmed by microscopic observation,stem cell phenotype analysis and lipogenic/osteogenic induction and differentiation.(2)The TWL and MWL values of CRPS-I rats were significantly decreased(P<0.05).After transplantation of BMSCs,the TWL and MWL values of rats from treatment group increased at 7,10 and 14 days after the operation(P<0.05).(3)The BDNF immunofluorescence intensity of the model group and the control group was significantly higher than that of the blank group(P<0.05).After BMSCs transplantation,the immunofluorescence intensity of BDNF in DRG of rats in the treatment group was significantly reduced,which was lower than the expression intensity of model group and control group(P<0.05).(4)The mRNA and protein expression of BDNF,CGRP,SP,TNF-,i1-6 in dorsal root ganglion of CRPS-I model rats was significantly higher than that of normal rats(P<0.05).After BMSCs transplantation,the mRNA and protein expression of these factors significantly decreased(P<0.05).(5)The expressions of Nav1.7,Nav1.8,and Navl.9mRNA and protein in the dorsal root ganglion tissues of rats in the CRPS-I model group were significantly higher than those in the blank group.BMSCs intrathecal injection transplantation can reduce the expression of Nav1.7,Nav1.8,and Nav1.9 in dorsal root ganglion tissues of rats.ConclusionsBMSCs transplantation can relief pain and hyperalgesia of CRPS-I rats.The mechanism may be related to reducing the release of neuropeptides and inflammatory cytokines in damaged nerve tissue and the inhibition of the activity of related subtypes in VGSCs.