Objective:To investigate the effects of repeated intrathecal administration of N-methyl-D-aspartate(NMDA)receptor antagonist on neuropathic pain in the spared nerve injury(SNI) rat models and to explore its mechanism. Methods:Totally 72 male Sprague-Dawley rats weighing 240-260 g were randomly divided into 6 groups(n=12 each):sham operation group(group S)

spared nerve injury group(group NP)

ketamine low-dose group(group K1)

ketamine high-dose group(group K2)

MK-801 low-dose group(group M1)

MK-801 high-dose group(group M2). In group S

the sciatic nerves and its branches were only exposed but not ligated.In other groups

neuropathic pain model was produced by spared nerve injury(SNI). In groups K1

K2

M1 and M2

ketamine 50 μg

ketamine 100 ug

MK-81 5 ug and MK-801 10 ug were injected intrathecally respectively

once a day for 7 days consecutively starting from 1 day after successful SNI surgery

while the equal volume of normal saline 10 μl was injected instead in S and NP groups. The paw withdrawal mechanical threshold(PWMT)was measured on 1 day before surgery and 1-7 days after surgery. Rats were sacrificed on 7 day after operation and the lumbar segments of the spinal cord(L4-6)were removed.The expression level of b FGF and GFAP were detected by immunohistochemistry;the expression level of b FGF was detected by Western blot. Results:The PWMT was significantly lower in group NP than in group S before and after intrathecal injection on 7 day(P=0.000). The PWMT was significantly higher in groups K1

K2

M1 and M2 than in group NP(P=0.000). Immunohistochemistry showed that protein expression of b FGF and GFAP was higher in groups NP than in group S(P=0.000). The protein expression of b FGF and GFAP was lower in groups K1

K2

M1 and M2 than in group NP(P=0.000). Western blot showed that protein expression of b FGF was in creased in groups NP than in group S(P=0.000). The protein expression of b FGF was decreased in groups K1

K2

M1 and M2 than in group NP(P=0.000).Conclusion:Intrathecal administration of NMDA receptor antagonist can reduce hyperalgesia induced by SNI and decreasing the protein expression level of bFGF and GFAP may be involved in the mechanism.