Ⅰ组代谢型谷氨酸受体拮抗剂对吗啡耐受大鼠热痛阈的影响

Effects of group Ⅰ metabotropic glutamate receptor antagonist on thermal pain threshold in morphine tolerant rats

目的观察鞘内注射Ⅰ组代谢型谷氨酸受体(mGluRs)拮抗剂对吗啡耐受大鼠热痛阈的影响。方法 36只雄性Spague-Dawley大鼠随机均分为6组,鞘内置管后第4天开始给药。0.9%氯化钠溶液组(C组)予0.9%氯化钠溶液10μL。吗啡耐受组(M组)予吗啡10μg。吗啡+1-胺塞茚满-1,5-二羟酸(AIDA)组(MA组)予吗啡10μg+AIDA60nmol。吗啡+2-甲基-6-苯基苯乙炔-吡啶(MPEP)组(MM组)予吗啡10μg+MPEP60nmol。AIDA组予AIDA60nmol。MPEP组予MPEP60nmol。连续给药7d,每天2次。给药前和给药后30min测定大鼠甩尾潜伏期(TFL)以观察各组热痛阈的变化。结果 M组在第1、2天的TFL显著高于C组(P值均<0.05),随着用药天数增加,M组TFL逐渐缩短,到第7天与C组的差异无统计学意义(P>0.05)。MA组和MM组的TFL也呈下降趋势,但明显缓于M组。MA组第3～7天的TFL高于MM组,但差异均无统计学意义(P值均>0.05)。AIDA组和MPEP组TFL的变化不大,与C组的差异均无统计学意义(P值均>0.05)。结论Ⅰ组mGluRs拮抗剂有抑制吗啡耐受的作用。

Objective To study the effect of intrathecally injected group Ⅰ metabotropic glutamate receptor （mGluRs） antagonist on the thermal pain threshold in morphine tolerant rats.Methods Male Sprague-Dawley rats were randomly divided into six groups with 6 rats in each.Four days after intrathecal catheterization the animals were given intrathecal （i.t.） administration of saline （10 μL）,morphine （10 μg）,morphine （10 μg） plus 1-aminoindan-1,5-dicarboxylic acid （AIDA,60 nmol）,morphine （10 μg） plus 2-methyl-6-phenylethynyl-pynidine （MPEP,60 nmol）,AIDA （60 nmol） or MPEP （60 nmol） twice a day for 7 consecutive days.Tail flick latency （TFL） was measured before and 30 min after drug administration to assess thermal pain threshold in each group.Results TFL of group M was significantly higher than that of group C on the 1 and 2 d （P0.05）,but decreased gradually thereafter;there was no significant difference between group M and C on 7 d （P0.05）.TFL of group MA and group MM decreased more slowly than that of group M.TFL of group MA was higher than that of group MM,especially during 3 to 7 d,but the difference between group MM and group MA was not significantly different.Conclusion Group Ⅰ mGluRs is involved in morphine tolerance and its antagonist can inhibit the development of morphine tolerance.（Shanghai Med J,2010,33：316-318）