Peng Bei, Guo Qulian, Wang Ping, Pan Yundan, Zou Wangyuan
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010 Nov;35(11):1167-73. doi: 10.3969/j.issn.1672-7347.2010.11.009.
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.
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.
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).
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.
观察鞘内注射核因子-κB（NF-κB）抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）对大鼠单关节炎（MA）模型疼痛敏感性阈值及脊髓CX3C趋化因子受体1（CX3CR1）表达的影响。
48只成功进行鞘内置管的Sprague-Dawley大鼠随机分为4组（每组12只）：（1）生理盐水假手术组（假手术组）；（2）生理盐水单关节炎组（MA组）；（3）MA前注射10 μL 100 μmol/L PDTC组（PDTC预处理组）；（4）MA后注射10 μL 100 μmol/L PDTC组（PDTC后处理组）。鞘内置管5 d后注射生理盐水或PDTC。在鞘内注射前后不同时间点测量4组大鼠的疼痛敏感性阈值。随后通过向大鼠左踝关节注射完全弗氏佐剂（CFA）建立大鼠单关节炎模型。鞘内注射后第3天，采用免疫组化法观察L₅脊髓节段小胶质细胞的表达，并取脊髓腰段L₄-L₅进行RT-PCR检测NF-κB mRNA和CX3CR1 mRNA的表达。
与MA组相比，鞘内注射后各时间点假手术组、PDTC预处理组和PDTC后处理组的疼痛敏感性阈值均显著升高（P<0.05），而L₅脊髓节段小胶质细胞显著减少（P<0.05），脊髓腰段L₄-L₅的CX3CR1 mRNA和NF-κB mRNA表达显著降低（P<0.05）。
鞘内注射NF-κB抑制剂PDTC可缓解CFA诱导的单关节炎模型的痛觉过敏效应。其机制可能与NF-κB信号通路有关，该通路通过调节CX3CR1表达参与炎性疼痛的形成。
