[Regulation of inflammatory pain by NF-κB and CX3CR1 at the spinal cord of rats].
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).


CONCLUSIONS
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.
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Bei
B
Peng
Qulian
Q
Guo
Ping
P
Wang
Yundan
Y
Pan
Wangyuan
W
Zou
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications*; D000073883:CX3C Chemokine Receptor 1; D007278:Injections, Spinal; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013859:Thiocarbamates / Q000008:administration & dosage
D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D016328:NF-kappa B; D011759:Pyrrolidines; D019707:Receptors, Chemokine; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid