NF-κB上调神经病理性疼痛大鼠脊髓CX3CR1表达

目的：观察鞘内注射核转录因子-κB（NF-κB）抑制剂吡咯烷二硫氨基甲酸（PDTC）对坐骨神经慢性挤压伤（CCI）大鼠痛阈和脊髓CX3CR1受体表达的影响.方法：60只成年雄性SD大鼠,体质量250～300g,鞘内置管成功后,随机分5组（n=12）：假手术＋生理盐水（sham组）、CCI＋生理盐水（CCI组）、假手术＋PDTC1000pmol/d（PDTC＋sham组）、CCI＋PDTC100pmol/d（PDTC＋CCI组1）、CCI＋PDTC1000pmol/d（PDTC＋CCI组2）.鞘内置管5d后开始鞘内输注生理盐水或不同剂量的PDTC,鞘内注射1d后建立大鼠CCI神经病理性疼痛模型或者假手术模型,分别于术前及术后不同时点测定5组大鼠的痛敏值,并在鞘内注射4d后取脊髓腰膨大部进行Western Blot实验检测CX3CR1的表达.结果：CCI组与sham组比较大鼠术后各时点痛敏阈值明显下降,并在术后第3日降至最低点（P〈0.05）,脊髓CX3CR1的表达明显升高（P〈0.01）.PDTC＋CCI组与CCI组比较,术后各时点大鼠痛敏阈值增高（P〈0.05）,脊髓CX3CR1的表达下降（P〈0.01）.结论：鞘内给予PDTC可减轻CCI大鼠的病理性疼痛,并抑制脊髓CX3CR1的表达.活化的NF-κB可能通过上调脊髓CX3CR1表达而参与了神经病理性疼痛的发生.

NF-κb up-regulates spinal CX3CR1 expression in neuropathic pain rats

AIM： To study the effects of intrathecal infusion of pyrrolidine dithiocarbamate （PDTC）, a nuclear factor-kappa B （NF-κB） inhibitor, on spinal CX3CR1 expression induced by sciatic chronic constriction injury （CCI） and its effects on the development of neuropathic pain in rat. METHODS： Sixty SD rats weighing 250-300 g were randomly divided into 5 groups （12 in each group） ： Sham ＋ 9 g/L Normal Saline （ NS ） group, CCI ＋ 9 g/L NS group, Sham ＋ PDTC 1000 pmol/d group, CCI ＋ PDTC 100 pmol/d group and CCI ＋ PDTC 1000 pmol/d group. After implanting intrathecal catheter for 5 d, PDTC or NS was intrathecally administrated once per day. One day later, CCI or sham operation was done and pain threshold was assessed daily. Rats in each group were sacrificed at 4 d after intrathecal infusion and spinal cord lumbar intumescentia expression of CX3CR1 was assessed by Western blotting. RESULTS： The pain threshold in CCI group significantly decreased compared with that in sham group 1 to 3 d after CCI and maximally decreased at day 3 after CCI（ P 〈 0.05 ）. The pain threshold in PDTC ＋ CCI group significantly increased compared with that in CCI group 1 to 3 d after CCI （ P 〈 0.05 ）. The expression of CX3CR1 in PDTC ＋ CCI group significantly decreased compared with those in CCI group （ P 〈 0. 01 ）. CONCLUSION： Intrathecal infusion of PDTC suppresses the spinal CX3CR1 expression and atternates CCI-induced neuropathie pain in rats. The activated NF-KB pathway may get involved in the development of neuropathic pain through up-regulating spinal CX3CR1 expression.