Background and objective

Emotional and cognitive impairments are common comorbidities of chronic neuropathic pain that significantly impact the quality of life of patients. While the nociceptive components of the peripheral nerve chronic constriction injury (CCI) animal model have been extensively analyzed, data related to the development of mood and cognitive disorders, and especially its impact on female rats remains fragmented. We systematically reviewed the literature analyzing the methods used to induce and evaluate the development of emotional- and cognitive-like impairments and sex-specific differences in the CCI model.

Databases and data treatment

We searched PubMed, Google Scholar and Web of Science from inception to September 30th, 2019, and a total of 44 papers were considered eligible for inclusion. We included animal studies assessing nociception, locomotion, anxious-like, depressive-like and cognitive behaviours after the CCI induction.

Results

The overall quality of the studies was considered moderate to high. Overall, the induction of CCI leads to the development of emotional impairments, namely anxiety- and depressive-like behaviours, as well as cognitive impairments. With the majority of the studies using male subjects, the lack of evidence on female animals prevents the evaluation of sex-specific differences.

Conclusions

This review supports the development of an anxiodepressive-like phenotype, associated with cognitive impairments, in CCI-induced animals. These results support the use of this animal model for the study of the mechanisms underlying these comorbidities, as well as a screening tool for the development/repurposing of drugs that tackle both the neuropathy-induced nociceptive and emotional impairments, such as tricyclic antidepressants. Importantly, our review also highlights the need for studies performed in female rodents as these are almost non-existent.

中文翻译：

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神经性疼痛周围神经慢性收缩损伤模型 (CCI) 中的情绪和认知障碍：系统评价

背景与目的

情绪和认知障碍是慢性神经性疼痛的常见合并症，严重影响患者的生活质量。虽然外周神经慢性收缩性损伤 (CCI) 动物模型的伤害性成分已被广泛分析，但与情绪和认知障碍的发展相关的数据，尤其是其对雌性大鼠的影响仍然零散。我们系统地回顾了分析用于诱导和评估情绪和认知障碍的发展以及 CCI 模型中性别特异性差异的方法的文献。

数据库和数据处理

我们从开始到 2019 年 9 月 30 日搜索了 PubMed、Google Scholar 和 Web of Science，共有 44 篇论文被认为符合纳入条件。我们纳入了评估 CCI 诱导后的伤害感受、运动、焦虑样、抑郁样和认知行为的动物研究。

结果

研究的整体质量被认为是中等至高。总体而言，CCI 的诱导导致情绪障碍的发展，即焦虑和抑郁样行为，以及认知障碍。由于大多数研究使用男性受试者，缺乏关于雌性动物的证据阻碍了对性别差异的评估。

结论

本综述支持在 CCI 诱导的动物中形成与认知障碍相关的抗焦虑样表型。这些结果支持使用该动物模型来研究这些合并症的潜在机制，以及用于开发/重新利用可解决神经病变引起的伤害性和情绪障碍的药物（如三环类抗抑郁药）的筛选工具。重要的是，我们的审查还强调了对雌性啮齿动物进行研究的必要性，因为这些研究几乎不存在。