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Clinical relevance of chronic neuropathic pain phenotypes in mice: A comprehensive behavioral analysis
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-12-05 , DOI: 10.1016/j.bbr.2020.113055
Nidhi Goswami 1 , Mohd Aleem 1 , Kailash Manda 1
Affiliation  

Despite a large number of preclinical studies performed each year, the safe and effective therapeutic interventions for chronic pain are scant. Therefore, it appears that pre-clinical modeling requires a systematically organized behavioral test paradigm to quantify the response of animals for a specific pain state. The present study, therefore, conceptualized a test battery to evaluate the behavioral changes in mice following neuropathic pain. We employed sciatic nerve chronic constriction injury (CCI) in C57BL/6 J mice to model chronic pain state. Mice were monitored for thermal hyperalgesia and grip strength for 30 days. Subsequently, mice underwent a behavioral test battery consisting of the nociceptive threshold, the affective and cognitive functions and motor coordination, and strength. Our results showed that CCI mice are insensitive to thermal stimuli. However, nerve-injured mice showed significant changes in neuromuscular coordination, basal anxiety, and hedonic state. Such impaired neuromuscular coordination is indicative of disability rather than the actual pain phenotype. While using the digital gait analysis, our study revealed rationales for the insensitivity of CCI mice to thermal stimuli. Our results suggest that the predictive validity of the CCI model necessitates a comprehensive behavioral test battery to select the clinically relevant and measurable phenotype to quantify chronic neuropathic pain.



中文翻译:

小鼠慢性神经性疼痛表型的临床相关性:综合行为分析

尽管每年进行大量临床前研究,但安全有效的慢性疼痛治疗干预措施很少。因此,临床前建模似乎需要一个系统组织的行为测试范式来量化动物对特定疼痛状态的反应。因此,本研究概念化了一个测试组来评估小鼠神经性疼痛后的行为变化。我们在 C57BL/6 J 小鼠中采用坐骨神经慢性收缩损伤 (CCI) 来模拟慢性疼痛状态。监测小鼠的热痛觉过敏和握力 30 天。随后,小鼠接受了一组行为测试,包括伤害感受阈值、情感和认知功能以及运动协调和力量。我们的结果表明 CCI 小鼠对热刺激不敏感。然而,神经损伤小鼠在神经肌肉协调、基础焦虑和快感状态方面表现出显着变化。这种受损的神经肌肉协调能力表明残疾而不是实际的疼痛表型。在使用数字步态分析时,我们的研究揭示了 CCI 小鼠对热刺激不敏感的基本原理。我们的结果表明,CCI 模型的预测有效性需要一个全面的行为测试组来选择临床相关和可测量的表型来量化慢性神经性疼痛。这种受损的神经肌肉协调能力表明残疾而不是实际的疼痛表型。在使用数字步态分析时,我们的研究揭示了 CCI 小鼠对热刺激不敏感的基本原理。我们的结果表明,CCI 模型的预测有效性需要一个全面的行为测试组来选择临床相关和可测量的表型来量化慢性神经性疼痛。这种受损的神经肌肉协调能力表明残疾而不是实际的疼痛表型。在使用数字步态分析时,我们的研究揭示了 CCI 小鼠对热刺激不敏感的基本原理。我们的结果表明,CCI 模型的预测有效性需要一个全面的行为测试组来选择临床相关和可测量的表型来量化慢性神经性疼痛。

更新日期:2020-12-16
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