瞬时感受器电位离子通道香草素受体4下游信号分子的确定及其对大鼠背根神经节慢性压迫后痛觉过敏的作用

Identification of transient receptor potential vanilloid 4 downstream signaling molecule and its effect in behavioural hyperalgesia following chronic compression of the dorsal root ganglion in rats

目的:探讨大鼠背根神经节慢性压迫CCD后瞬时感受器电位离子通道香草素受体4(TRPV4)下游信号分子及其在痛觉过敏中的机制。方法:鞘内分别注射TRPV4拮抗剂钌红(RR)、TRPV4反义寡脱氧核苷酸(ASODN)和一氧化氮合成酶(NOS)抑制剂L-NAME,检测CCD大鼠背根神经节DRG内一氧化氮(NO)代谢产物亚硝酸盐(nitrite)含量变化,并观测热刺激缩爪反应潜伏期(PWL)的变化。结果:鞘内分别注射RR、TRPV4 AS ODN和L-NAME后,均能够显著降低CCD大鼠DRG内亚硝酸盐含量(P<0.05),CCD大鼠的热痛敏行为也能够显著改善(P<0.05)。结论:TRPV4及其下游信号分子NO参与介导CCD大鼠的热痛觉过敏。

Objective：To investigate transient receptor potential vanilloid 4（TRPV4） downstream signaling molecule and its effect in behavioural hyperalgesia following chronic compression of dorsal root ganglion （DRG） （CCD） in rats. Method：Intrathecal administration of ruthenium red （RR,TRPV4 antagonist）,TRPV4 antisense oligodeoxynucleotide（ODN）（TRPV4 AS ODN） or L-NAME （inhibitor of NO synthase） were adopted to study the thermal stimuli paw withdrawl latency （PWL） and the nitrite （an index of nitric oxide formation） production in the DRG of CCD rats. Result：Intrathecal administration of RR TRPV4 AS ODN or L-NAME induced significant increase of PWL（P0.05） and significant decrease of nitrite in DRG（P0.05）,compared with control rats,respectively. Conclusion：TRPV4-NO pathway is involved in thermal hyperalgesia in CCD rats.