CD3+ T cells are critical for the resolution of comorbid inflammatory pain and depression-like behavior.
CD3+ T cells are critical for the resolution of comorbid inflammatory pain and depression-like behavior.
复制标题
DOI：
10.1016/j.ynpai.2020.100043
复制
发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Kavelaars, Annemieke
中科院分区：
文献类型：
--
作者：
Laumet, Geoffroy;Edralin, Jules D;Kavelaars, Annemieke
背景：慢性疼痛和抑郁症常常同时发生。这种共病的潜在机制尚未完全了解。在此，我们研究了CD3 + T细胞在小鼠共病性持续性机械性异常性疼痛、自发性疼痛和抑郁样行为的炎症模型中的作用。
方法：比较C57Bl/6野生型和Rag2 - / -小鼠对足底注射完全弗氏佐剂（CFA）的反应。分别通过冯弗雷纤维丝、条件性位置偏爱和强迫游泳试验评估机械性异常性疼痛、自发性疼痛和抑郁样行为。
结果：在缺乏适应性免疫细胞的Rag2 - / -小鼠中，机械性异常性疼痛、自发性疼痛和抑郁样行为的缓解明显延迟。在CFA注射前用野生型小鼠的CD3 + T细胞对Rag2 - / -小鼠进行重建，使疼痛和抑郁样行为指标的缓解恢复正常。T细胞对疼痛和抑郁样行为指标的发作或严重程度没有影响。T细胞的缺乏不影响爪子、脊髓和大脑中的细胞因子表达，这表明延迟缓解并非由长期（神经）炎症所致。
结论：我们的研究结果表明，T细胞对于炎症刺激后机械性异常性疼痛、自发性疼痛和抑郁样行为的自然缓解至关重要。这种T细胞介导的缓解途径的失调可能导致慢性疼痛和抑郁症的共病。
意义：慢性疼痛和抑郁症经常与炎症迹象相关。然而，全身性免疫抑制不足以解决共病性疼痛和抑郁症。在此我们证明，在周围炎症模型中，T细胞是解决共病性持续性机械性异常性疼痛、自发性疼痛和抑郁症所必需的，这表明免疫系统可对这些共病的发作和缓解都有作用。增强T细胞的促缓解作用可能对治疗共病性持续性疼痛和抑郁症患者有重大影响。
BACKGROUND: Chronic pain and depression often co-occur. The mechanisms underlying this comorbidity are incompletely understood. Here, we investigated the role of CD3+ T cells in an inflammatory model of comorbid persistent mechanical allodynia, spontaneous pain, and depression-like behavior in mice.METHODS: C57Bl/6wt and Rag2 -/- mice were compared in their response to intraplantar administration of complete Freund's adjuvant (CFA). Mechanical allodynia, spontaneous pain and depression-like behavior were assessed by von Frey, conditioned place preference and forced swim test respectively.RESULTS: Resolution of mechanical allodynia, spontaneous pain, and depression-like behavior was markedly delayed in Rag2 -/- mice that are devoid of adaptive immune cells. Reconstitution of Rag2 -/- mice with CD3+ T cells from WT mice before CFA injection normalized the resolution of indicators of pain and depression-like behavior. T cells did not contribute to onset or severity of indicators of pain and depression-like behavior. The lack of T cells did not affect cytokine expression in the paw, spinal cord and brain, indicating that the delayed resolution was not resulting from prolonged (neuro)inflammation.CONCLUSIONS: Our findings show that T cells are critical for the natural resolution of mechanical allodynia, spontaneous pain, and depression-like behavior after an inflammatory challenge. Dysregulation of this T cell-mediated resolution pathway could contribute to the comorbidity of chronic pain and depression.SIGNIFICANCE: Chronic pain and depression are frequently associated with signs of inflammation. However, general immunosuppression is not sufficient to resolve comorbid pain and depression. Here we demonstrate that T cells are required for resolution of comorbid persistent mechanical allodynia, spontaneous pain, and depression in a model of peripheral inflammation, indicating the immune system can contribute to both onset and resolution of these comorbidities. Enhancing pro-resolution effects of T cells may have a major impact to treat patients with comorbid persistent pain and depression.