预先给予酪氨酸激酶抑制剂IPTRK3对神经源性疼痛的影响  

Effects of TrkA inhibitor IPTRK3 pretreatment on neuropathic pain

作　　者：马伟英[1] 何惠燕[2] 纪风涛[1] 刘玲[1] 梁建军[1] 广濑宗孝[3] 曹铭辉[1] 

机构地区：[1]中山大学孙逸仙纪念医院麻醉科,广东广州510120 [2]中山大学孙逸仙纪念医院消毒供应中心,广东广州510120 [3]福井大学医学部麻醉和复苏科

出　　处：《中国药理学通报》2011年第10期1439-1443,共5页Chinese Pharmacological Bulletin

基　　金：广东省科技计划资助项目(No2010B080701004);广东省医学科研基金资助项目(NoB2010092)

摘　　要：目的探讨预先给予酪氨酸激酶(tyrosine kinase,Tr-kA)抑制剂IPTRK3对神经源性疼痛的抑制作用及其可能作用机制。方法建立小鼠坐骨神经部分结扎(partial sciaticnerve ligation,PSNL)模型,术前10 min单次腹腔给予IPTRK3 10 mg·kg-1,测定给药前后不同时间点小鼠的热痛觉过敏阈值(paw withdrawal latency,PWL)和机械痛觉过敏阈值(paw withdrawal threshold,PWT),免疫印迹法测量左侧L4-5背根神经节瞬时感受器电位香草酸受体1(transient re-ceptor potential vanilloid 1,TRPV1)的表达情况,免疫组织化学染色法测定Fos蛋白在L4-5脊髓背角的表达变化。结果与假手术(sham)组相比,PSNL组小鼠出现明显热、机械痛觉过敏(P<0.05),背根节TRPV1蛋白表达及脊髓背角Fos蛋白阳性神经元数目明显增多(P<0.05)。与PSNL组相比,预先给予IPTRK3 10 mg·kg-1明显减轻小鼠热痛觉过敏,背根神经节TRPV1蛋白表达水平及脊髓背角Fos蛋白阳性神经元数目明显降低(P<0.05),但仍明显高于sham组(P<0.05)。结论预先给予IPTRK3可以明显减轻神经源性疼痛症状,抑制背根神经节TRPV1及脊髓背角Fos蛋白的表达可能部分参与其早期迅速减轻伤害性刺激信息传递。Aim To investigate the inhibitory effects of pretreatment TrkA inhibitor IPTRK3 on neuropathic pain induced by partial sciatic nerve ligation（PSNL）and its possible mechanisms.Methods Partial sciatic nerve ligation models were established in mice.All drugs were injected intraperitoneally 10 min before surgery.Paw Withdrawal Latency（PWL）and 50% Paw Withdrawal Threshold（PWT） were measured at different time points pre or post drug administration.Dorsal root ganglions（DRG） of Left L4-5 were removed for determination of TRPV1 protein expression with Western blot,and L4-5 spinal dorsal horn tissues were removed for analyzing the expression of Fos protein by immunohistochemistry.Results Compared with sham group 2 h after surgery,mice in PSNL group developed a robust thermal and mechanical hyperalgesia and TRPV1 in DRG and Fos protein expressions in spinal dorsal horn were increased;compared with PSNL group,TrkA inhibitor IPTRK3 obviously attenuated thermal hyperalgesia and significantly suppressed the expression of TRPV1 in DRG and Fos protein in spinal dorsal horn.Conclusion Pre-emptive administration of IPTRK3 obviously inhibits the up-regulation of TRPV1 in DRG and Fos protein in spinal dorsal horn,which may be possibly associated with its rapid anti-hyperalgesia effects in PSNL model of neuropathic pain.

关 键 词：TRKA IPTRK3 坐骨神经部分结扎 神经源性疼痛 TRPV1 FOS蛋白 

分 类 号：R-332[医药卫生] R322.8