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神经病理性疼痛大鼠模型中自发行为改变的特征——疼痛评估的新结局指标?

Characterization of alterations in spontaneous behaviors in a rat model of neuropathic pain - new outcome measures for pain evaluation?

作者信息

Liptáková Annamária, Castelhano-Carlos M J, Fiúza-Fernandes Juliana, Sousa Nuno, Roche Michelle, Finn David P, Leite-Almeida Hugo

机构信息

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.

出版信息

Front Behav Neurosci. 2025 Jun 6;19:1550476. doi: 10.3389/fnbeh.2025.1550476. eCollection 2025.

Abstract

Chronic pain affects all life domains including social interaction and responding. The aim of this study was to track spontaneous behaviors in an experimental chronic pain model to uncover alternative pain indicators in a socially and physically enriched home-cage setting. The spared nerve injury (SNI) was used to model neuropathic pain in Wistar Han male and female rats housed in the PhenoWorld (PhW). Spontaneous behavior of animals was recorded in their home cages once a week following SNI during both the dark and light phases of the light-dark cycle using focal sampling in order to assess alterations induced by neuropathic pain. Males and females with SNI demonstrated significantly lower threshold to von Frey test (VF) in the ipsilateral hind paws compared to sham controls. SNI significantly increased huddling time in both males and females during light and dark phases. Males showed increased grooming and play fighting during the dark phase compared to females while during the light phase females huddled significantly more than males. No significant effects were observed on other behaviors analyzed. This study showed that peripheral nerve injury has an impact on spontaneous behavior, specifically on huddling. This finding provides new perspective into pain evaluation and suggests the possibility of considering spontaneous behavior as an additional method of assessing pain-related behavior in rodents. To bridge the current gap between basic research and development of novel analgesics, there is a need to develop non-evoked behavioral assays to investigate changes in animal wellbeing and spontaneous pain. Our findings raise the possibility of discovering new outcome measures, however, additional study to reverse these behaviors with analgesics should be conducted.

摘要

慢性疼痛会影响包括社交互动和反应在内的所有生活领域。本研究的目的是在实验性慢性疼痛模型中追踪自发行为,以在社会和身体环境丰富的饲养笼环境中发现替代疼痛指标。采用保留神经损伤(SNI)法在PhenoWorld(PhW)饲养的Wistar Han雄性和雌性大鼠中模拟神经性疼痛。在SNI术后,每周一次在明暗周期的黑暗和明亮阶段,使用焦点取样法在动物的饲养笼中记录其自发行为,以评估神经性疼痛引起的变化。与假手术对照组相比,SNI雄性和雌性大鼠同侧后爪对von Frey测试(VF)的阈值显著降低。SNI显著增加了雄性和雌性大鼠在黑暗和明亮阶段的抱团时间。与雌性相比,雄性在黑暗阶段的梳理毛发和打斗玩耍行为增加,而在明亮阶段,雌性抱团行为比雄性显著更多。在分析的其他行为上未观察到显著影响。本研究表明,周围神经损伤会影响自发行为,特别是对抱团行为的影响。这一发现为疼痛评估提供了新的视角,并表明有可能将自发行为作为评估啮齿动物疼痛相关行为的一种额外方法。为了弥合当前基础研究与新型镇痛药研发之间的差距,需要开发非诱发行为测定法来研究动物健康和自发疼痛的变化。我们的研究结果增加了发现新结局指标的可能性,然而,应该进行额外的研究以用镇痛药逆转这些行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc8/12179769/4a68632fc378/fnbeh-19-1550476-g001.jpg

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