Basic mechanisms of pre-emptive analgesia

我研究了预先给药对慢性收缩性损伤（CCI）或部分坐骨神经结扎（PSNL）引起的热过敏发展的影响。本研究使用的药物有吗啡（mu阿片受体激动剂）、克拉定（α -2受体激动剂）、MK-801 （NMDA拮抗剂）、n-硝基- l -精氨酸甲酯（L-NAME； NOS抑制剂）、YM022（胆囊收缩素b拮抗剂）。这些药物在神经损伤前10-20分钟给予鞘内。CCI是通过在大鼠坐骨神经周围进行四次松散结扎而形成的。PSNL是通过将大鼠坐骨神经的三分之一到二分之一紧密结扎而产生的。在CCI模型中，可乐定、mk-801和L-NAME延缓了热觉过敏的发生，而吗啡和yk022则没有。在PSNL模型中，我只研究了MK-801的作用，MK-801对热性过敏的发展没有影响。提示α -2受体激动剂、NMDA受体拮抗剂和NOS抑制剂预处理可对CCI模型产生先发制人的镇痛作用。

I investigated the effects of pre-emptively administered drugs on the development of thermal hypersthesia induced by chronic contriction injury (CCI) or partial sciatic nerve ligation (PSNL). Drugs used in this study were morphine (mu opioid agonist), clonidine (alpha-2 agonist), MK-801 (NMDA antagonist), N-nitro-L-arginine methyl ester (L-NAME ; NOS inhibitor), YM022 (cholecystokinin-B antagonist). These drugs were administered intrathecally 10-20-min before the nerve injury. CCI was created by making four loose ligatures around the rat sciatic nerve. PSNL was created by making tight ligation around one-third to one-half of the rat sciatic nerve. In the CCI model, clonidine, mk-801 and L-NAME,but not morphine and yk022, delayd the development of thermal hyperesthesia. In the PSNL model, I investigated only the effect of MK-801 and MK-801 had no effect on the development of themal hypersthesia. These results suggested theat pre-treatment of alpha-2 receptor agonist, NMDA receptor antagonist and NOS inhibitor may produce pre-emptive analgesia in CCI model.