The Experiment Study On The Mechanisms Of Therapeutic Effects Of Ketamine On The Chronic Neuropathic Pain

Part I Effect of intrathecal ketamine on neuronal nitric oxide synthase activity of the spinal dorsal horn in a rat model of chronic constriction injury(CCI).Objective To evaluate the effects of intrathecal (i.t.) administration of ketamine on neuronal nitric synthase activity of the spinal dorsal horn in a rat model of chronic constriction injury (CCI).Methods Thirty-six SD rats weighing 160 ~ 180g were randomly divided into 6 grotips of 6 animals each: in group I the animals were shamly operated, i.t. normal saline 20μL; in group lithe rats were placed four loose ligatures around the sciatic nerve and i.t. normal saline 20μL; in group III,IV,V,VI, ketamine 12.5μg,50μg 100μg,300μg was administered 30min before and 1,2,3 days after operation. Rats were tested for hyperalgesia by measuring paw withdrawal latency (PWL) using von-Frey filaments and ice-cold water.The animals were decapitated 14 days after operation.The L4-L6 lumbar spinal cord was quickly removed and the spinal dorsal horn was dissected on ice. Results In group II and III, PWL and NOS activity were significantly higher than group I (P<0.01) ; NOS activity was not significantly increased in group IV,V,VI as compared with those of sham operated animals (P>0.05) ;There were statistically significant differences between group IV,V,VI and group II;There was no significant difference in PWL,NOS activity among group III,IV, V,VI. Conclusion NO/NOS may contribute to the development of neuropathic pain of CCI rats, and this process might be associated with NMDA receptor.