分析重复脊柱手术引起的 Sprague-Dawley 大鼠疼痛标志物和硬膜外纤维化。

Analysis of pain markers and epidural fibrosis caused by repeated spinal surgery in Sprague-Dawley rats.

机构信息

Department of Pathophysiology, School of Basic Medical Sciences, Beihua University, Jilin, 132021, China.

Department of Orthopedics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 64, Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea.

出版信息

BMC Musculoskelet Disord. 2021 Jan 5;22(1):16. doi: 10.1186/s12891-020-03920-z.

DOI:10.1186/s12891-020-03920-z

PMID:33402133

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7786924/

Abstract

BACKGROUND

Epidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen - activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis.

METHODS

Sprague-Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord.

RESULTS

Dural thickness was 6.363 ± 1.911 μm in group A, 13.238 ± 2.123 μm in group B and 19.4 ± 2.115 μm in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting.

CONCLUSIONS

Repeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.

摘要

背景

硬膜外纤维化是脊柱翻修手术后疼痛的病因之一。有报道称，丝裂原活化蛋白激酶（MAPK）家族的特定成员可能介导神经病理性疼痛。然而，反复脊柱手术引起的硬膜外纤维化和与疼痛相关的蛋白在引起脊柱手术后综合征中的作用尚不清楚。本研究使用大鼠脊柱手术硬膜外纤维化和粘连模型，评估并研究了疼痛标志物与硬膜外纤维化之间的关系。

方法

对接受脊柱手术的 Sprague-Dawley 大鼠进行分组：A 组（单次椎板切除术）、B 组（两次重复手术）和 C 组（三次重复手术）。测量每组实验大鼠的硬脑膜厚度，并对脊髓进行丝裂原活化蛋白激酶（ERK、p38 和 JNK）的免疫组织化学分析和 Western blot 分析。

结果

A 组硬脑膜厚度为 6.363±1.911μm，B 组为 13.238±2.123μm，C 组为 19.4±2.115μm。Western blot 分析显示，磷酸化 ERK 的表达随重复手术次数的增加而逐渐增加，B 组（1.77 倍）和 C 组（2.42 倍）的表达均高于 A 组。磷酸化 p38 的表达呈增加趋势，B 组（1.17 倍）和 C 组（1.33 倍）的表达均高于 A 组。然而，磷酸化 JNK 的表达并未随重复手术次数的增加而逐渐增加，B 组（1.62 倍）和 C 组（1.43 倍）的表达均高于 A 组。免疫组织化学分析显示，除磷酸化 JNK 外，磷酸化 ERK 和 p38 在脊柱背角的表达随重复手术次数的增加而逐渐增加，Western blot 分析结果与之相符。