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步态分析作为大鼠碘乙酸盐诱导的膝关节疼痛慢性期的一种稳健的疼痛行为终点。

Gait analysis as a robust pain behavioural endpoint in the chronic phase of the monoiodoacetate-induced knee joint pain in the rat.

机构信息

School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Queensland, Australia.

Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.

出版信息

Behav Pharmacol. 2022 Feb 1;33(1):23-31. doi: 10.1097/FBP.0000000000000663.

Abstract

The monoiodoacetate-induced rat model of osteoarthritis knee pain is widely used. However, there are between-study differences in the pain behavioural endpoints assessed and in the dose of intraarticular monoiodoacetate administered. This study evaluated the robustness of gait analysis as a pain behavioural endpoint in the chronic phase of this model, in comparison with mechanical hyperalgesia in the injected (ipsilateral) joint and development of mechanical allodynia in the ipsilateral hind paws. Groups of Sprague-Dawley rats received a single intraarticular injection of monoiodoacetate at 0.5, 1, 2 or 3 mg or vehicle (saline) into the left (ipsilateral) knee joint. An additional group of rats were not injected (naïve group). The pain behavioural methods used were gait analysis, measurement of pressure algometry thresholds in the ipsilateral knee joints, and assessment of mechanical allodynia in the ipsilateral hind paws using von Frey filaments. These pain behavioural endpoints were assessed premonoiodoacetate injection and for up to 42-days postmonoiodoacetate injection in a blinded manner. Body weights were also assessed as a measure of general health. Good general health was maintained as all rats gained weight at a similar rate for the 42-day study period. In the chronic phase of the model (days 9-42), intraarticular monoiodoacetate at 3 mg evoked robust alterations in multiple gait parameters as well as persistent mechanical allodynia in the ipsilateral hind paws. For the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis knee pain, gait analysis, such as mechanical allodynia in the ipsilateral hind paws, is a robust pain behavioural measure.

摘要

碘乙酸单盐诱导的膝骨关节炎疼痛大鼠模型被广泛应用。然而,在评估的疼痛行为终点和关节内注射的碘乙酸单盐剂量方面,不同研究之间存在差异。本研究评估了步态分析作为该模型慢性期疼痛行为终点的稳健性,与注射(同侧)关节的机械性痛觉过敏和同侧后爪的机械性痛觉过敏发展进行比较。将 Sprague-Dawley 大鼠分组,在左(同侧)膝关节内单次注射 0.5、1、2 或 3 mg 碘乙酸单盐或载体(生理盐水)。另一组大鼠未接受注射(未处理组)。使用的疼痛行为方法包括步态分析、测量同侧膝关节的压力测痛阈值,以及使用 von Frey 纤维评估同侧后爪的机械性痛觉过敏。这些疼痛行为终点在碘乙酸单盐注射前和注射后长达 42 天进行盲法评估。还评估了体重作为一般健康状况的衡量标准。良好的总体健康状况得以维持,因为所有大鼠在 42 天的研究期间以相似的速度增加体重。在模型的慢性期(第 9-42 天),3 mg 的关节内碘乙酸单盐引起了多种步态参数的明显改变,并伴有同侧后爪持续的机械性痛觉过敏。对于碘乙酸单盐诱导的膝骨关节炎疼痛大鼠模型的慢性期,步态分析(如同侧后爪的机械性痛觉过敏)是一种稳健的疼痛行为测量方法。

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