N-3 fatty acids modulate repeated stress-evoked pain chronicity
N-3 fatty acids modulate repeated stress-evoked pain chronicity
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DOI：
10.1016/j.brainres.2019.03.001
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发表时间：
2019-07-01
期刊：
影响因子：
2.9
通讯作者：
Tokuyama, Shogo
中科院分区：
文献类型：
--
作者：
Aizawa, Fuka;Sato, Shumpei;Tokuyama, Shogo
N-3脂肪酸，包括二十二碳六烯酸(DHA)，对疼痛和精神障碍都有有益的影响。事实上，我们先前报道，应激诱导的疼痛延长可能是通过抑制G蛋白偶联受体40/游离脂肪酸受体1(GPR40/FFAR1)介导的，而GPR40/FFAR1是由DHA和长链脂肪酸激活的。然而，GPR40/FFAR1配体在应激诱导的慢性疼痛的发生中的作用尚未被描述。在这项研究中，我们利用饮食诱导的n-3脂肪酸缺乏的小鼠，研究了DHA在应激性疼痛慢性化中的作用。N-3脂肪酸缺陷小鼠在反复暴露于社会失败压力后，表现出焦虑样行为的加剧。完整的n-3脂肪酸缺陷小鼠的爪阈值降低。另一方面，失败但不是非应激的n-3脂肪酸缺陷小鼠的爪子退出阈值一直持续到爪子手术后第49天。我们评估了重复应激诱发的慢性疼痛模型小鼠大脑中磷脂酰胆碱成分的变化，这些小鼠没有服用n-3脂肪酸缺乏的饮食。在爪子手术后的第7天，含有DHA和其他长链脂肪酸的磷脂酰胆碱在应激小鼠的大脑中被发现减少。此外，口服DHA可改善应激诱导的持续性机械异位痛。这些结果表明，慢性应激可能直接影响脑脂成分；相关变化可能参与慢性疼痛的发生。我们的发现表明，n-3脂肪酸，特别是DHA，是治疗压力引起的慢性疼痛的潜在靶点。
N-3 fatty acids, including docosahexaenoic acid (DHA), have a beneficial effect in both pain and psychiatric disorders. In fact, we previously reported that stress-induced pain prolongation might be mediated through the suppression of the G-protein coupled-receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which is activated by DHA and long-chain fatty acids. However, the involvement of GPR40/FFAR1 ligands in the development of stress-induced chronic pain has not yet been described. In this study, we investigated the role of DHA in stress-evoked pain chronicity using diet-induced n-3 fatty acid deficient mice. The n-3 fatty acid deficient mice showed exacerbation of anxiety-like behavior after repeated exposure to social defeat stress. The intact n-3 fatty acid deficient mice showed a decrease in paw threshold values. On the other hand, paw withdrawal thresholds of defeated but not non-stressed, n-3 fatty acid deficient mice continued until day 49 after paw surgery. We evaluated changes in phosphatidylcholine composition in the brains of repeat stress-evoked chronic pain model mice which were not on n-3 fatty acid deficiency diets. On day 7 after paw surgery, phosphatidylcholines with DHA and other long-chain fatty acids were found to have decreased in the brains of stressed mice. Moreover, stress-induced persistent mechanical allodynia was improved by oral DHA supplementation. These results indicated that chronic stress may directly affect brain lipid composition; the related changes could be involved in chronic pain development. Our findings suggested that n-3 fatty acids, particularly DHA, are useful as a potential therapeutic target for stress-evoked chronic pain.