Abstract: Objective To study the effect of N-methyl-d-aspartate(NMDA)receptor antagonist-MK-801 on pain threshold and serum melatonin content of the mice after amputation of tail extremity and to provide experimental data for the study on plastic changes in central nervous system after amputation. Methods The mice with amputated distal tail of 2.5cm were served as the experiment model of amputation.The latencies of the mice licking their hindpaw s on the hot plate (55±1℃)were recorded at 0.5 hr,1 hr,2 hr,3 hr,1 day,and 1 week after the amputation and were used as indexes of pain threshold.If the mice did not respond within 60 seconds,the mice were removed from the hot plate,and the latency was recorded as 60 s.MK-801 was injected via caudalis vein.The blood of the mice was obtained by cutting the heads after the hot plate experiment.The serum melatonin contents were measured with enzyme-linked immunoabsorbent assay. Results Compared with that of control group(18.24±5.06 s,n=15)and before the amputation(18.40±5.42 s,n=15),the pain threshold was not obviously changed at 0.5 hr and 1 hr after the amputation(P>0.05),but was significantly increased at 2 hr(23.78±3.57,n=15,P<0.01),3 hr(22.42±6.71 s,n=15,P<0.05),and 1 day and 1 week after the amputation (P>0.05).Compared with that of the control group(155.750±61.577 pg/ml,n=10),the serum melatonin content 2 hr after the amputation was significantly decreased(82.207±19.871 pg/ml,n=9,P<0.05).The intravenous injection of MK-801 antagonized both the increase of pain threshold(15.41±7.00 s,n=9)and the decrease of serum melatonin content (131.783±36.637 pg/ml,n=7)2 hr after the amputation. Conclusion The results indicate that NMDA receptor is involved in the processes of the increase in pain threshold and the decrease in serum melatonin content induced by amputation in mice.