Basic mechanisms of pre-emptive analgesia

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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.