Departments of Anesthesiology and.
Neuroscience, Washington University in St. Louis, St. Louis, MO, United States.
Pain. 2021 Jun 1;162(6):1705-1721. doi: 10.1097/j.pain.0000000000002179.
Pain puts patients at risk for developing psychiatric conditions such as anxiety and depression. Preclinical mouse models of pain-induced affective behavior vary widely in methodology and results, impairing progress towards improved therapeutics. To systematically investigate the effect of long-term inflammatory pain on exploratory behavior and stress coping strategy, we assessed male C57BL/6J mice in the forced swim test (FST), elevated zero maze, and open field test at 4 and 6 weeks postinjection of Complete Freund's Adjuvant, while controlling for testing order and combination. Inflammatory pain did not induce a passive stress coping strategy in the FST and did not reduce exploratory behavior in the elevated zero maze or the open field test. Using systematic correlational analysis and composite behavioral scores, we found no consistent association among measures for mice with or without inflammatory pain. A meta-analysis of similar studies indicated a modest, significant effect of Complete Freund's Adjuvant on exploratory behavior, but not immobility in the FST, and high heterogeneity among effect sizes in all 3 paradigms. Given the urgency for understanding the mechanisms of pain comorbidities and identifying novel therapies, these findings support the reallocation of our limited resources away from such unreliable assays and toward motivated and naturalistic behaviors. Future studies in pain and psychiatric translational research may benefit by considering outcomes beyond binary categorization, quantifying the associations between multiple measured behaviors, and agnostically identifying subtle yet meaningful patterns in behaviors.
疼痛使患者面临发展出精神疾病的风险，如焦虑和抑郁。疼痛引起的情感行为的临床前小鼠模型在方法和结果上差异很大，这阻碍了改善治疗方法的进展。为了系统地研究长期炎症性疼痛对探索性行为和应激应对策略的影响，我们在注射完全弗氏佐剂后 4 周和 6 周时，使用强迫游泳试验 (FST)、高架十字迷宫和旷场试验评估雄性 C57BL/6J 小鼠，同时控制测试顺序和组合。炎症性疼痛不会在 FST 中诱导被动的应激应对策略，也不会减少高架十字迷宫或旷场试验中的探索性行为。通过系统的相关分析和综合行为评分，我们发现有或没有炎症性疼痛的小鼠之间的测量值之间没有一致的关联。对类似研究的荟萃分析表明，完全弗氏佐剂对探索性行为有适度的显著影响，但对 FST 中的不动性没有影响，而且在所有 3 种范式中，效应大小的异质性都很高。考虑到理解疼痛合并症的机制和确定新疗法的紧迫性，这些发现支持将我们有限的资源从这些不可靠的检测中重新分配，转而关注积极主动和自然的行为。疼痛和精神科转化研究中的未来研究可能会受益于考虑超出二元分类的结果，量化多个测量行为之间的关联，并在行为中识别微妙但有意义的模式。
