| Part 1 The Effect of NMD A Receptor Antagonist on the Expression of bFGF in Spinal Dorsal Horn of Rat with Neuropathic PainObjectiv To investigate the effects of repeated intrathecal administration NMDA receptor antagonist on neuropathic pain in the spared nerve injury rat model and to explore its mechanism.Methods Seventy-two male Sprague-Dawley rats were randomly divided into 6 group(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. In groups K1, K2, M1 and M2, ketamine 50ug, ketamine 100ug, MK-81 5ug and MK-801 lOug were injected by catheter in subarachnoid respectively, once a day for 7 days consecutively starting from 1day after successful SNI surgery. While the equal volume of normal saline 10 ul was injected instead in S and NP groups. The paw withdrawal mechanical threshold was measured at 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 bFGF and GFAP were detected by immuno-histochemistry; the expression level of bFGF were detected by Western blot.Results Compared with group S, The level of PWMT was significantly decreased and the expression of bFGF and GFAP was higher in group NP (P<0.05). Compared with group NP, The level of PWMT was significantly increased in groups K1, K2, M1 and M2 and the expression of bFGF and GFAP was lower in groups K1, K2, M1 and M2 than in group NP(P<0.05).Conclusion The repeated 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.Part 2 The Effect of bFGF on the Expression of NMDA Receptor in Spinal Cord of Rat with Neuropathic PainObjective To investigate the role of basic fibroblast growth factor and its effect on the expression of N-methyl-D-aspartate receptor subunit in rat spinal cord with neuropathic pain.Methods Forty-eight male SD rats were randomly divided into four groups (n=12):sham group (group A), sham+ bFGF antibody group (group B), neuropathic pain group (group C), neuropathic pain+bFGF antibody group (group D). Neuropathic pain model was produced by spared nerve injury. bFGF antibody 18 ug (40 ul) was injected intrathecally on 1,6,9,13, 16 and 20 days after operation in group B and D. The equal volume of phosphate buffered saline was injected intrathecally in group A and C at the same time. The paw withdrawal mechanical threshold was measured on 1, 4,7,14 and 21 days after operation and 1 day before operation. Rats in each group were sacrificed on 21d after operation and the lumbar segments of the spinal cord (L4-6) were collected. The expression level of glial fibrillary acidic protein was detected by immunohistochemical analysis; The expression of N-methyl-D-aspartate receptor 1 subunit (NR1), N-methyl-D-aspartate receptor 2 subunit (NR2A or NR2B) were detected by RT-PCR and Western blot.Results Compared with group A and B, the level of PWMT was decreased and the expression of GFAP, NR1 and NR2B in spinal cord was increased in group C and D (P<0.05). Compared with group C, the level of PWMT was increased and the expression of GFAP, NR1 and NR2B in spinal cord was decreased in group D (P<0.05).Conclusion Intrathecal injection of bFGF antibody can relieve neuropathic pain in rats with SNI, and such an effect might be correlated with the modulation of NMDA receptor. |
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