Emerging evidence indicates that CXCL12/CXCR4 signaling involves in chronic ***,little study has systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying *** this study we foun...
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Emerging evidence indicates that CXCL12/CXCR4 signaling involves in chronic ***,little study has systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying *** this study we found that spared nerve injury(SNI)resulted in an increased expression of CXCL12 and its cognate receptor CXCR4 in L5 DRG neurons and satellite glial *** also aroused a long-lasting upregulation of CXCL12 and CXCR4 in ipsilateral L4-5 spinal cord dorsal horn,which characterized by CXCL12 expressed in neurons and CXCR4 colocalized with neurons and ***,SNI induced sustained increased expression of TNF-αin DRG and spinal *** injection(i.p.)of TNF-α-synthesis inhibitor thalidomide,reduced the SNI-induced mechanical hypersensitivity,and inhibited the expression of CXCL12 in DRG and spinal *** injection(i.t.)of CXCR4 antagonist AMD3100,began on 30 min before or 7 days after SNI,both resulted in reduction of behavioral signs of *** treated by a bolus *** ***3100 on 8th day of SNI attenuated abnormal pain *** established neuropathic pain following SNI was also impaired by CXCL12 neutralizing antibody i.t..Moreover,repetitive AMD3100 *** the activation of ERK in spinal *** CXCL12 i.t.-induced mechanical hypersensitivity in nave rats was alleviated by pretreatment with MEK inhibitor ***,our results revealed that TNF-αmediated the upregulation of CXCL12 in DRG and spinal cord following SNI,and the CXCL12/CXCR4 signailing via ERK activation contributed to the development and maintenance of neuropathic pain.
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