Regulation of inflammatory pain by NF-κB and CX3CR1 at the spinal cord of rats / 中南大学学报(医学版)

ABSTRACT

OBJECTIVE@#To observe the effect of intrathecal injection of nuclear factor-κB (NF-κB) inhibitor of pyrrolidine dithiocarbamate (PDTC) on pain sensitivity thresholds and the expression of spinal cord CX3C chemokine receptor 1 (CX3CR1) in monoarthritis (MA) model in rats.@*METHODS@#Forty-eight Sprague-Dawley rats were randomly divided into 4 groups (12 each) after successful intrathecal catheterization (1) sham operation with physiological saline group (the sham group); (2) MA with normal saline group (the MA group); (3) 10 μL 100 μmol/L PDTC before MA (the PDTC pre-treatment group); (4)MA before 10 μL 100 μmol/L PDTC (the PDTC post-treatment group). Normal saline or PDTC was injected 5 d after the intrathecal catheterization. Pain sensitivity thresholds were measured in the 4 groups before and after the intrathecal injection at different time points. Rat monoarthritis model was subsequently built by injecting complete Freund's adjuvant (CFA) into the left ankle joint of the rats. On day 3 after the intrathecal injection, expression of microglia in the L₅ spinal cord segment was observed by immunohistochemical method, and the lumbar segments L₄-L₅ of spinal cord were taken to perform RT-PCR to examine the expression of NF-κB mRNA and CX3CR1 mRNA.@*RESULTS@#Compared with the MA group, the pain sensitivity thresholds in the sham group, the PDTC pre-treatment group and the PDTC post-treatment group at each time point after the intrathecal injection increased significantly (P<0.05), while microglia in the L₅ spinal cord segment decreased significantly (P<0.05) and expression of CX3CR1 mRNA and NF-κB mRNA in the lumbar segments L₄-L₅ of spinal cord decreased significantly (P<0.05).@*CONCLUSION@#The hyperalgesic effect of the CFA-induced model of monoarthritis can be relieved by intrathecal injection of NF-κB inhibitor PDTC. Its mechanism is possibly related to NF-κB signal pathway which is involved in the formation of inflammatory pain through regulating CX3CR1 expression.