Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain

Shen Qian; Gao Jin; Chen Ping

doi:10.13406/j.cnki.cyxb.000678

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Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain

更新时间：2024-01-17

- Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain
- Journal of Chongqing Medical University Vol. 41, Issue 1, Pages: 50-55(2016)
- 作者机构：
  
  重庆医科大学附属第一医院麻醉科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.000678
  CLC： R741
- Published：2016，
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[1]沈茜,高进,陈萍.NMDA受体拮抗剂对神经病理性疼痛大鼠脊髓背角bFGF表达的影响[J].重庆医科大学学报,2016,41(01):50-55.

Shen Qian, Gao Jin, Chen Ping. Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain. [J]. Journal of Chongqing Medical University 41(1):50-55(2016)
[1]沈茜,高进,陈萍.NMDA受体拮抗剂对神经病理性疼痛大鼠脊髓背角bFGF表达的影响[J].重庆医科大学学报,2016,41(01):50-55. DOI： 10.13406/j.cnki.cyxb.000678.

Shen Qian, Gao Jin, Chen Ping. Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain. [J]. Journal of Chongqing Medical University 41(1):50-55(2016) DOI： 10.13406/j.cnki.cyxb.000678.

摘要

目的 :探讨鞘内间断多次给予N-甲基-D-天门冬氨酸（N-methyl-D-aspartate

NMDA）受体拮抗剂对坐骨神经分支选择性损伤模型（spared nerve injury

SNI）大鼠神经病理性疼痛的缓解作用及其可能的机制。方法:雄性SD大鼠72只

体质量240

60 g

采用随机数字表法

将大鼠随机分为6组（n=12）:假手术组（S组）、坐骨神经分支选择性损伤组（NP组）、氯胺酮低剂量组（K1组）、氯胺酮高剂量组（K2组）、MK-801低剂量组（M1组）、MK-801高剂量组（M2组）。S组仅暴露坐骨神经

NP组、K1组、K2组、M1组、M2组制备坐骨神经分支选择性损伤模型。从术后1 d开始

K1组、K2组、M1组、M2组鞘内分别注射氯胺酮50μg、氯胺酮100μg、MK-801 5μg和MK-801 10μg

容量均为10μl

S组和NP组鞘内注射生理盐水10μl

1次/d

连续给药7 d。分别于术前1 d和术后1

进行疼痛行为学观察和机械刺激缩足反射阈值（paw withdrawal mechanical threshold

PWMT）测定。所有大鼠均于术后第7天处死

免疫组化观察大鼠脊髓L4

节段背角胶质纤维酸性蛋白（glial fibrillary acidic protein

GFAP）和碱性成纤维细胞生长因子（basic fibroblast growth factor

b FGF）表达变化

Western blot检测脊髓L4

节段b FGF蛋白含量变化。结果:术后第7天给药前和给药后

NP组术侧PWMT较S组明显降低（P=0.000）

K1组、K2组、M1组和M2组术侧PWMT较NP组明显升高（P=0.000）。免疫组化结果显示

NP组术侧b FGF、GFAP蛋白表达量较S组明显升高（P=0.000）;K1组、K2组、M1组和M2组bFGF、GFAP蛋白表达量较NP组明显降低（P=0.000）。Western blot结果显示

NP组b FGF蛋白表达量较S组明显升高（P=0.000）;K1组、K2组、M1组和M2组b FGF蛋白表达量较NP组明显降低（P=0.000）。结论:鞘内间断多次给予NMDA受体拮抗剂可缓解SNI引起的大鼠痛觉过敏

其机制可能与抑制b FGF蛋白表达及星形胶质细胞活化有关。

Abstract

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

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

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

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

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.

关键词

碱性成纤维细胞生长因子氯胺酮MK-801神经病理性疼痛

Keywords

basic fibroblast growth factorketamineMK-801Neuropathic pain

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