In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review.
In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review.
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小鼠体内椎间盘退变模型及其作为临床椎间盘源性背痛转化模型的应用：比较回顾。
DOI：
10.3389/fpain.2022.894651
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
腰痛是全球残疾的主要原因，研究表明椎间盘（IVD）退变是一个主要的风险因素。虽然已经开发了许多体外模型并用于研究IVD病理生理学和治疗策略，但IVD变性的病因是一个复杂的多因素过程，涉及附近组织的串扰和全身效应。因此，使用适当的体内模型是必要的，以充分了解相关的分子，结构和功能的变化，以及它们如何与疼痛。与其他动物模型相比，小鼠模型由于可获得性和易于遗传操作而被广泛采用。尽管它们的尺寸小，但小鼠腰椎间盘在几何形状、结构和机械特性方面与人类IVD具有显著的相似性。虽然存在几种不同的IVD变性小鼠模型，但诱导变性的方法的更大标准化和一组一致的输出测量的开发可以使小鼠模型成为临床转化的更强大工具。本文回顾了目前的小鼠模型的IVD退化的背景下，临床翻译，并强调了一套重要的输出测量研究疾病病理学或筛选再生疗法，重点是疼痛表型。首先，我们将这些模型归纳和分类为遗传、年龄相关和机械诱导。然后，比较这些模型中评估的结果参数，包括诱发性和自发性疼痛的分子、细胞、功能/结构和疼痛评估。这些比较突出了一组潜在的关键参数，这些参数可用于验证模型，并告知其筛选IVD变性的潜在治疗方法及其对人体状况的转化。由于症状性疼痛的治疗是重要的，这篇综述强调了小鼠的关键疼痛样行为评估，并探讨了目前与椎间盘源性背痛相关的行为评估。总体而言，确定特定的研究问题对于确定相关模型至关重要，其中组织学染色，成像，细胞外基质成分，力学和疼痛是评估变性和再生策略的关键参数。
Low back pain is a leading cause of disability worldwide and studies have demonstrated intervertebral disc (IVD) degeneration as a major risk factor. While many in vitro models have been developed and used to study IVD pathophysiology and therapeutic strategies, the etiology of IVD degeneration is a complex multifactorial process involving crosstalk of nearby tissues and systemic effects. Thus, the use of appropriate in vivo models is necessary to fully understand the associated molecular, structural, and functional changes and how they relate to pain. Mouse models have been widely adopted due to accessibility and ease of genetic manipulation compared to other animal models. Despite their small size, mice lumbar discs demonstrate significant similarities to the human IVD in terms of geometry, structure, and mechanical properties. While several different mouse models of IVD degeneration exist, greater standardization of the methods for inducing degeneration and the development of a consistent set of output measurements could allow mouse models to become a stronger tool for clinical translation. This article reviews current mouse models of IVD degeneration in the context of clinical translation and highlights a critical set of output measurements for studying disease pathology or screening regenerative therapies with an emphasis on pain phenotyping. First, we summarized and categorized these models into genetic, age-related, and mechanically induced. Then, the outcome parameters assessed in these models are compared including, molecular, cellular, functional/structural, and pain assessments for both evoked and spontaneous pain. These comparisons highlight a set of potential key parameters that can be used to validate the model and inform its utility to screen potential therapies for IVD degeneration and their translation to the human condition. As treatment of symptomatic pain is important, this review provides an emphasis on critical pain-like behavior assessments in mice and explores current behavioral assessments relevant to discogenic back pain. Overall, the specific research question was determined to be essential to identify the relevant model with histological staining, imaging, extracellular matrix composition, mechanics, and pain as critical parameters for assessing degeneration and regenerative strategies.
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影响因子：
2.4
作者：
Bailey, Jeannie F.;Hargens, Alan R.;Lotz, Jeffrey C.
通讯作者：
Lotz, Jeffrey C.
影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
4.6
作者：
Cao Y;Liao S;Zeng H;Ni S;Tintani F;Hao Y;Wang L;Wu T;Lu H;Duan C;Hu J
通讯作者：
Hu J
影响因子：
4.9
作者：
Binch AL;Cole AA;Breakwell LM;Michael AL;Chiverton N;Creemers LB;Cross AK;Le Maitre CL
通讯作者：
Le Maitre CL
影响因子：
3.7
作者：
Brenner DS;Golden JP;Gereau RW 4th
通讯作者：
Gereau RW 4th