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作为血友病性关节炎关节痛的动物模型,重复自体关节内血液注射。

Repeated autologous intraarticular blood injections as an animal model for joint pain in haemophilic arthropathy.

出版信息

Arthritis Res Ther. 2013 Oct 7;15(5):R148. doi: 10.1186/ar4331.

DOI:10.1186/ar4331
PMID:24286243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3978931/
Abstract

INTRODUCTION

Haemophilic arthropathy following recurrent joint bleedings is one of the major disease-related complications in people with haemophilia (PWH), leading to mostly chronic joint pain. Since many antinociceptive principles interfere with the clotting system, PWH are restricted in treatment options, thereby defining a medical need for novel therapeutic principles. However, we lack the availability of an animal model for joint pain in haemophilic arthropathy for testing these.

METHODS

In this study, we aimed to validate the rat model of repeated autologous intraarticular blood injections specifically for pain-related behavior. During an observation period of 50 days, groups of animals were injected weekly into one knee joint with either whole blood or cellular/plasma components.

RESULTS

Injections induced primary hyperalgesia starting after the third injection, accompanied by mild functional gait changes and joint swelling. Secondary hyperalgesia and quantitative gait disturbances were not observed. This phenotype was most prominent in whole blood injected animals, with effect sizes of cells and plasma being additive. In order to differentiate haemophilia-related arthropathy from traumatic joint bleeding, another group was injected with whole blood only once, which did not cause any alterations.

CONCLUSIONS

Repeated autologous intraarticular injections of blood showed a time course, inflammatory response and reduction in pain thresholds similar to the signs and symptoms observed in PWH. Therefore, this model may be utilised in the future for testing novel antinociceptive principles in haemophilia-associated joint pain.

摘要

简介

反复关节出血导致的血友病性关节病是血友病患者(PWH)的主要疾病相关并发症之一,主要导致慢性关节疼痛。由于许多镇痛原则会干扰凝血系统,PWH 的治疗选择受到限制,因此需要新的治疗原则。然而,我们缺乏用于测试这些原则的血友病性关节病关节痛的动物模型。

方法

在这项研究中,我们旨在验证反复自体关节内血注的大鼠模型是否特别适用于与疼痛相关的行为。在 50 天的观察期内,每周向一组动物的一个膝关节内注射全血或细胞/血浆成分。

结果

注射后第 3 次开始引起原发性痛觉过敏,伴有轻度功能步态改变和关节肿胀。未观察到继发性痛觉过敏和定量步态障碍。这种表型在注射全血的动物中最为明显,细胞和血浆的作用大小呈相加性。为了将血友病相关性关节病与创伤性关节出血区分开来,另一组仅注射全血一次,并未引起任何变化。

结论

反复自体关节内血注显示出与 PWH 观察到的体征和症状相似的时间过程、炎症反应和疼痛阈值降低。因此,该模型将来可能用于测试血友病相关性关节痛的新型镇痛原则。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/db7f7a5199cb/ar4331-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/0f44b26d4eb2/ar4331-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/de22cdd4d748/ar4331-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/db7f7a5199cb/ar4331-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/0f44b26d4eb2/ar4331-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/de22cdd4d748/ar4331-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4015/3978931/db7f7a5199cb/ar4331-3.jpg

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Pain. 2011 Sep;152(9):2029-2035. doi: 10.1016/j.pain.2011.04.030. Epub 2011 May 25.
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Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.局部微出血促进了白细胞介素-6(IL-6)和白细胞介素-17(IL-17)依赖型关节炎的发生,而这一过程并不依赖于活化 T 细胞对组织抗原的识别。
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