鞘内注射GABA转运体-1抑制剂NO-711对CCI大鼠脊髓背角pERK表达的影响

Effects of NO-711 administered intrathecally on phospho-extracellular signal-regulated kinase induced by chronic constriction injury(CCI) of the sciatic nerve in rats

目的观察γ-氨基丁酸(GABA)转运体-1(GAT-1)抑制剂NO-711对坐骨神经慢性松结扎(CCI)大鼠机械和热痛阈及脊髓背角神经元磷酸化细胞外信号调节激酶(pERK)表达的影响,探讨NO-711在脊髓水平抗痛敏的机制。方法雄性SD大鼠126只,随机均分为六组(n=21):CCI+NO-711 50μg组(N50组)、CCI+NO-711 100μg组(N100组)、CCI+NO-711 200μg组(N200组)、CCI+生理盐水组(CN组)、CCI组、假手术组(S组)。CCI组和S组在术前、术后1、3、5、7、14、21 d测定大鼠机械缩腿阈值(MWT)和热缩腿潜伏期(TWL);其余各组大鼠在手术前5 d先进行鞘内置管,CCI手术后5 d鞘内注射不同剂量的NO-711或生理盐水,测定给药前、给药后30 min、1、2、4、8 h大鼠MWT、TWL及脊髓背角pERK表达的变化。结果 CCI组MWT和TWL术后3 d后各时点较术前2 d均降低和缩短、且相应时点均低于和短于S组(P<0.01);与给药前比较,CN组大鼠各时点MWT和TWL差异无统计学意义,而NO-711各剂量组大鼠给药后MWT和TWL均呈剂量依赖性增加;与CCI组和NS组比较,NO-711对脊髓背角pERK表达呈剂量依赖性抑制。结论鞘内注射NO-711能明显抑制CCI大鼠机械痛敏和热痛敏及脊髓背角pERK表达,提示pERK介导NO-711在脊髓水平具有抗痛敏效应。

Objective To observe the effects of NO-711 administered intrathecaliy on the mechanical and heat hyperalgesia and the expression of pERK induced by CCI of the sciatic nerve in rats, and investigate the possible mechanism of NO-711 antinoeiceptive transmission at the spinal level. Methods One hundred and twenty six male Sprague-Dawley rats were randomized into six groups （n=21） ： CCI ＋ NO-711 50μg （N50）, CCI ＋ NO-7ll 100μg （N100）, CCI ＋ NO-711 200 μg （N200）, CCI ＋ normal saline group （CN）, CCI, and sham operation （S）. The mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） in S and CCI groups were measured before operation and 1, 3, 5, 7, 14 and 21 d after operation, respectively. Rats in NS0, N100, N200 or CN groups were intrathecally cathetered 5 d before operation and administered with NO-711 or saline 5 d after CCI. The nociceptive thresholds and pERK expression in the spinal dorsal horn were measured before and after administration 30 rain, 1, 2, 4 and 8 h, respectively. Results CCI group formed steady mechanical and heat hyperalgeia from 1 d to 21 d after operation. Intrathecal administration of NO-711can increase the MWT and TWL in a dose-dependent pattern. NO-711 inhibited the expression of pERK in a dose-dependent pattern. Conclusion Intrathecal NO-711 can reduce the mechanical and heat hyperalgesia of rats via the inhibition of expression of pERK followingCCL.