脊髓背角神经元瞬时受体电位离子通道1在大鼠神经病理性痛维持中的作用

Role of transient receptor potential ion channel 1 in spinal dorsal horn neurons in maintenance of neuropathic pain in rats

目的 评价脊髓背角神经元瞬时受体电位离子通道1（TRPA1）在大鼠神经病理性痛维持中的作用.方法 清洁级雄性SD大鼠56只,体重200 ～ 250 g,采用随机数字表法,将其分为4组（n=14）：假手术组（S组）、慢性背根神经节压迫组（CCD组）、CCD＋二甲基亚砜组（D组）和CCD＋TRPA1阻断剂HC-030031组（H组）.CCD组、D组、H组行CCD术；D组和H组在CCD术后7d时分别鞘内注射10％二甲基亚砜20μl或HC-030031 50 μg.分别于术前1 d（T0）、鞘内给药前1 h（T1）、鞘内给药后1 h（T2）、2 h（T3）、4 h（T4）、6 h（T5）、8 h（T6）、24 h（T7）时测定机械缩足反应阈（PWMT）.分别于T4、T7时处死6只大鼠,取L3-5脊髓组织,采用Western blot法测定TRPA1表达.结果 与S组比较,CCD组及D组T1-7时PWMT降低,T4、T7时脊髓组织TRPA1表达上调,H组T1、T5-7时PWMT降低,T7时脊髓组织TRPA1表达上调（P＜0.05）；与CCD组比较,H组T2-5时PWMT升高,T4时脊髓组织TRPA1表达下调（P＜0.05）.结论 脊髓背角神经元TRPA1参与了大鼠神经病理性痛的维持.

Objective To evaluate the role of transient receptor potential ion channel 1 （TRPA1） in the spinal dorsal horn neurons in maintenance of neuropathic pain in rats.Methods Fifty-six adult male SpragueDawley rats,weighing 200-250 g,were randomly divided into 4 groups （n =14 each）：sham operation group （group S）; chronic compression of dorsal root ganglia （CCD） group; CCD ＋ dimethyl sulfoxide group （group D）; and CCD ＋ TRPA1 blocker HC-030031 group （group H）.CCD was produced by infiltrating the L5 intervertebral foramen with 50 μl of a hemostatic matrix （SURGIFLO） in anesthetized rats in CCD,D and H groups.In D and H groups,10% dimethyl sulfoxide 20 μl and HC-030031 50 μg were injected intrathecally at 7 days after CCD operation,respectively.Paw withdrawal threshold to mechanical stimulation （PWMT） was measured at 1 day before operation （T0）,at 1 h before intrathecal administration （T1）,and at 1,2,4,6,8,and 24 h after intrathecal administration （T2-7）.Six rats in each group were sacrificed at T4 and T7,the L3-5 segments of the spinal cord were obtained for determination of TRPA1 expression in the spinal cord by Western blot.Results Compared with group S,PWMT was significantly decreased at T1-7,the expression of TRPA1 in the spinal cord was up-regulated at T4 and T7 in CCD and D groups,and the PWMT was decreased at T1 and T5-7 and the expression of TRPA1 was up-regulated at T7 in H group （P 〈 0.05）.Compared with CCD group,the PWMT was significantly increased at T2-5 and the expression of TRPA1 was down-regulated at T4 in H group （P 〈 0.05）.Conclusion TRPA1 in the spinal dorsal horn neurons is involved in the maintenance of neuropathic pain in rats.