The rostral ventromedial medulla (RVM) is a crucial structure in the descending pain modulatory system, playing a key role as a relay for both the facilitation and inhibition of pain. The chronic social defeat stress (CSDS) model has been widely used to study stress-induced behavioral impairments associated with depression in rodents. Several studies suggest that CSDS also causes changes related to chronic pain. In this study, we aimed to investigate the involvement of the RVM in CSDS-induced behavioral impairments, including those associated with chronic pain. We used chemogenetics to activate or inhibit the RVM during stress. The results indicated that the RVM is a vital hub influencing stress outcomes. Rostral ventromedial medulla activation during CSDS ameliorates all the stress outcomes, including social avoidance, allodynia, hyperalgesia, anhedonia, and behavioral despair. In addition, RVM inhibition in animals exposed to a subthreshold social defeat stress protocol induces a susceptible phenotype, facilitating all stress outcomes. Finally, chronic RVM inhibition-without any social stress stimulus-induces chronic pain but not depressive-like behaviors. Our findings provide insights into the comorbidity between chronic pain and depression by indicating the involvement of the RVM in establishing social stress-induced behavioral responses associated with both chronic pain and depression.

中文翻译：

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头端腹内侧延髓调节由社会压力引起的疼痛和抑郁相关行为。

延髓头端腹内侧（RVM）是下行疼痛调节系统中的关键结构，在促进和抑制疼痛方面发挥着关键的中继作用。慢性社交挫败压力（CSDS）模型已被广泛用于研究与啮齿类动物抑郁相关的压力引起的行为障碍。多项研究表明，CSDS 还会引起与慢性疼痛相关的变化。在这项研究中，我们旨在调查 RVM 在 CSDS 引起的行为障碍中的作用，包括与慢性疼痛相关的行为障碍。我们使用化学遗传学来激活或抑制压力期间的 RVM。结果表明，RVM 是影响压力结果的重要枢纽。 CSDS 期间头端腹内侧延髓激活可改善所有应激结果，包括社交回避、异常性疼痛、痛觉过敏、快感缺失和行为绝望。此外，暴露于阈下社交失败应激方案的动物的 RVM 抑制会诱发易感表型，促进所有应激结果。最后，慢性 RVM 抑制（没有任何社会压力刺激）会引起慢性疼痛，但不会引起抑郁样行为。我们的研究结果表明 RVM 参与建立与慢性疼痛和抑郁相关的社会压力诱发的行为反应，从而深入了解慢性疼痛和抑郁之间的共病。