Basic mechanisms of pre-emptive analgesia

我研究了预先给药对慢性收缩损伤(CCI)或部分坐骨神经结扎(PSNL)引起的热过敏的影响。本研究所用药物为吗啡(Mu阿片类激动剂)、可乐定(α-2激动剂)、N-硝基-L-精氨酸甲酯(L-NAME；一氧化氮合酶抑制剂)、YM022(缩胆囊素B拮抗剂)。这些药物在神经损伤前10-20分钟鞘内注射。CCI是通过在大鼠坐骨神经周围松散地结扎四条线而形成的。PSNL是通过紧密结扎大约三分之一到一半的大鼠坐骨神经而产生的。在CCI模型中，可乐定、MK-801和L-NAME延缓了热感觉过敏的发展，而吗啡和YK022无此作用。在PSNL模型中，我只观察了MK-801和MK-801对热感觉过敏发展的影响。提示在CCI模型中预先给予α-2受体激动剂、NMDA受体拮抗剂和NOS抑制剂可产生超前镇痛作用。

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.