丙戊酸钠参与脊髓水平疼痛-瘙痒调控的研究

目的 探讨丙戊酸钠( VPA)对小鼠坐骨神经分支高选择结扎切断 ( SNI)引起的神经病理性疼痛与氯喹诱发的急性瘙痒的影响. 方法 实验一:将昆明种雄性小鼠48 只随机分为6组:神经病理性疼痛组( SNI)、假手术组( Sham)、瘙痒组( CQ)、瘙痒溶媒组( NS)、疼痛瘙痒组( SQ)及空白对照组( CON);CON、SNI、Sham、SQ组在术前1 d,术后1、3、5、7、9、10 d测定左后足机械痛阈值(MWT),CON、CQ、NS、SQ组分别于右后足足底注射氯喹或生理盐水后观察小鼠舔足时间. 实验二:昆明种雄性小鼠16 只随机分为 SQ-V组和SQ-N组. SNI模型分别于术后5、6、7、8、9 d早晚8 时注射VPA( SQ-V 组)及VPA溶媒生理盐水( SQ-N组)后测定疼痛行为学,于术后第10天注射氯喹后观察瘙痒行为学. 行为检测结束后使用反转录PCR( RT-PCR)法检测脊髓L4-L6部位组蛋白去乙酰化酶2 ( HDAC2 )的表达. 结果 SNI组及SQ组在术后1 d MWT降低( P<0. 05 ) ,第5天仍在较低水平. SQ-V组较SQ-N组鞘注后MWT显著升高( P<0. 05 ).CQ组较NS组舔足时间显著延长,SQ组舔足时间明显低于CQ组(P<0. 05). SQ-V组舔足时间显著高于SQ-N组(P<0. 05). RT-PCR结果提示SNI引起HDAC2表达上调,CQ引起HDAC2表达下调. 结论 疼痛能够抑制瘙痒神经信号传导,脊髓水平HDAC2差异性表达介导疼痛-瘙痒的共同调节.

Sodium valproate involves in regulation of pain and itching in spinal cord

Objective To investigate the impact of VPA on pain behavior induced by SNI and itch behavior evoked by chloroquine. Methods Experiment 1:forty-eight male KM mice were randomly divided into SNI group, Sham group, CQ group, NS group, pain, SQ group and CON group. Pain threshold ( MWT) of the left hindpaw was measured 1 day before and 1, 3, 5, 7, 9, 10 day after operation in CON, SNI, Sham and SQ group. The licking time was observed after chloroquine or saline injection into the plantar surface of the right hindpaw in CON, CQ, NS and SQ group. Experiment two: sixteen male KM mice were randomly divided into SQ-V group and SQ-N group. Pain behaviors were measured after injection of VPA (SQ-V) and vehicle (SQ-N) at 8 AM and 8 PM on 5, 6, 7, 8, 9 day after SNI operation. Itching behavior was observed after injection of chloroquine on the 10th day af-ter SNI operation. The expression of histone deacetylase 2 (HDAC2) in spinal L4-L6 was detected by RT-PCR af-ter behavior testing. Results MWT following SNI was significantly lower ( P <0. 05 ) 1 day postoperation and reached the peak on the 5th day postoperation in SNI group and SQ group. MWT was significantly higher ( P <0. 05) after intrathecal injection in SQ-V group than in SQ-N group. Licking time was significantly longer in CQ group than in NS group, and licking time was significantly shorter in SQ group than in CQ group ( P <0. 05 ) . Licking time was significantly longer in SQ-V group than in SQ-N group ( P<0. 05 ) . The results of RT-PCR indi-cated that the expression of HDAC2 was upregulated after SNI and downregulated after CQ injection. Conclusion Pain can suppress the transmitting of itching signal, and differential expression of HDAC2 contributes to co-regula-tion of pain and itching in spinal cord.