Burek Dominika J, Massaly Nicolas, Yoon Hye Jean, Doering Michelle, Morón Jose A
Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States.
Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States.
Pain. 2022 May 1;163(5):809-819. doi: 10.1097/j.pain.0000000000002467.
Many analgesics inadequately address the psychiatric comorbidities of chronic and persistent pain, but there is no standard preclinical model of pain-altered behavior to support the development of new therapies. To explore this conflicting and inconclusive literature, we conducted a focused systematic review and meta-analysis on the effect of complete Freund adjuvant-induced (CFA) rodent hind paw inflammation on multiple classical indicators of exploratory behavior, stress coping, and naturalistic behavior. Our primary objective was to define CFA's effect on assays including, but not limited to, the elevated plus maze and forced swim test. Our secondary objective was to discover how variables such as species and strain may influence outcomes in such assays. We searched Ovid MEDLINE, Embase, Scopus, and Web of Science in April and October 2020 for studies with adult rodents injected with CFA into the hind paw and subsequently tested for aspects of "anxiety-like" or "depressive-like" behaviors. Forty-four studies evaluated performance in the elevated plus or zero maze, open field test, light-dark box, place escape and avoidance paradigm, forced swim test, tail suspension test, sucrose preference test, wheel running, and burrowing assay. Complete Freund adjuvant modestly but significantly decreased exploratory behavior, significantly increased passive stress coping in the tail suspension test but not the forced swim test, and significantly decreased preference for sucrose and naturally rewarding activity. Subgroup analyses revealed significant differences between species and animal sourcing. Based on the evidence provided here, we conclude future studies should focus on CFA's effect on natural rewards and naturalistic behaviors.
许多镇痛药无法充分解决慢性持续性疼痛的精神共病问题，但目前尚无标准的临床前疼痛行为改变模型来支持新疗法的开发。为了探究这一相互矛盾且尚无定论的文献，我们针对弗氏完全佐剂（CFA）诱导的啮齿动物后爪炎症对探索行为、应激应对和自然行为的多个经典指标的影响进行了重点系统综述和荟萃分析。我们的主要目标是确定CFA对包括但不限于高架十字迷宫和强迫游泳试验等检测方法的影响。我们的次要目标是发现物种和品系等变量如何影响此类检测的结果。我们于2020年4月和10月在Ovid MEDLINE、Embase、Scopus和科学网中搜索了有关将CFA注射到成年啮齿动物后爪并随后测试其“焦虑样”或“抑郁样”行为方面的研究。44项研究评估了在高架十字或零迷宫、旷场试验、明暗箱、位置逃避和回避范式、强迫游泳试验、悬尾试验、蔗糖偏好试验、转轮运动和掘洞试验中的表现。弗氏完全佐剂适度但显著地降低了探索行为，在悬尾试验中显著增加了被动应激应对，但在强迫游泳试验中没有，并且显著降低了对蔗糖的偏好和自然奖赏活动。亚组分析揭示了物种和动物来源之间的显著差异。基于此处提供的证据，我们得出结论，未来的研究应关注CFA对自然奖赏和自然行为的影响。
