腰椎终板微骨折损伤可导致 Modic 样改变、椎间盘退变和脊髓致敏 - 一种体内大鼠模型。

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - an in vivo rat model.

机构信息

Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1188, New York, NY 10029 USA; Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu 210006, China; Department of Orthopedic Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA.

Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1188, New York, NY 10029 USA.

出版信息

Spine J. 2023 Sep;23(9):1375-1388. doi: 10.1016/j.spinee.2023.04.012. Epub 2023 Apr 21.

DOI:10.1016/j.spinee.2023.04.012

PMID:37086976

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10524828/

Abstract

BACKGROUND CONTEXT

Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics.

PURPOSE

Establish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord.

STUDY DESIGN/SETTING: In vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors.

METHODS

EP-injury was induced in 5 month-old male Sprague-Dawley rats L4-5 and L5-6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and μCT, and spinal cord SubP.

RESULTS

Surgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization.

CONCLUSIONS

Surgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions.

CLINICAL SIGNIFICANCE

This rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

摘要

背景

椎间盘终板（EP）损伤在疼痛性椎间盘退变中起着关键作用，因为 Modic 改变（MCs）与疼痛高度相关。需要建立进展为疼痛状态的 EP 微骨折模型，以更好地了解病理生理机制并筛选治疗方法。

目的

建立体内大鼠腰椎 EP 微骨折模型，并评估椎间盘、椎体和脊髓之间的串扰。

研究设计/设置：采用体内大鼠 EP 微骨折损伤模型，对椎间盘退变、椎体重塑、脊髓 P 物质（SubP）和疼痛相关行为进行特征描述。

方法

通过在颅向椎体和 EP 上方穿刺进入椎间盘 NP，然后向椎间盘内注射 TNFα（n=7）或 PBS（n=6），在 5 月龄雄性 Sprague-Dawley 大鼠 L4-5 和 L5-6 椎间盘上诱导 EP 损伤，与假手术（无 EP 损伤手术，n=6）相比。评估 EP 损伤模型的椎间盘高度、组织学退变、疼痛样行为（后爪 von Frey 和前爪握力试验）、腰椎 MRI 和 μCT 以及脊髓 SubP。

结果

用 PBS 和 TNFα 注射诱导的手术 EP 微骨折引起椎间盘退变，表现为椎间盘高度降低和 MRI T2 信号降低、椎体重塑以及损伤附近软骨 EP 的继发性损伤。两个 EP 损伤组在缺陷周围均显示出类似于 MC 的变化，在 T1 加权 MRI 上呈低信号，在 T2 加权 MRI 上呈高信号，提示 MC 1 型。EP 损伤导致明显的足底撤回阈值降低、轴向握力降低和脊髓 SubP 增加，提示轴向脊髓不适和机械性超敏反应以及脊髓敏化。