The involvement of free fatty acid-GPR40/FFAR1 signaling in chronic social defeat stress-induced pain prolongation in C57BL/6J male mice
The involvement of free fatty acid-GPR40/FFAR1 signaling in chronic social defeat stress-induced pain prolongation in C57BL/6J male mice
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DOI：
10.1007/s00213-018-4930-8
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发表时间：
2018-08-01
影响因子：
3.4
通讯作者：
Tokuyama, Shogo
中科院分区：
文献类型：
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作者：
Aizawa, Fuka;Nakamoto, Kazuo;Tokuyama, Shogo
理由：抑郁和焦虑会导致慢性疼痛的发展。然而，情绪障碍诱发慢性疼痛的机制尚不清楚。之前，我们证明了大脑中G蛋白偶联受体40/游离脂肪酸受体1 （GPR40/FFAR1）信号传导与疼痛和情绪的调节有关。在本研究中，我们证明了GPR40/FFAR1信号在慢性疼痛发生中的作用是由情绪障碍诱导的。重复社会失败应激小鼠表现出社会互动和焦虑行为的损害。与非sd小鼠相比，这些小鼠在割爪后也引起疼痛延长。在SD应激期间，输注GPR40/FFAR1拮抗剂GW1100后，这种疼痛延长明显持续，而非SD应激期间则没有。然而，在SD应激时注入GW1100并未引起情绪行为的恶化。此外，gw1100治疗的sd小鼠在割爪后表现出强烈的情绪障碍倾向。我们的研究结果表明，大脑潜在应激条件下脂肪酸- gpr40 /FFAR1信号的功能障碍可能与慢性疼痛的发生有关。
Rationale Depression and anxiety can cause the development of chronic pain. However, the mechanism of chronic pain induced by emotional dysfunction is still unknown. Previously, we demonstrated that the G protein-coupled receptor 40/ free fatty acid receptor 1 (GPR40/FFAR1) signaling in the brain is related to regulation of both pain and emotion. In the present study, we proved that the role of GPR40/FFAR1 signaling in the development of chronic pain is induced by emotional dysfunction. Repeated social defeat (SD)-stressed mice showed the impairment of social interaction and anxiety behavior. These mice also caused pain prolongation after paw-incision comparison with non-SD mice. This pain prolongation was markedly continued by infusion of the GPR40/FFAR1 antagonist, GW1100 during SD stress but not non-SD stress. Although, infusion of the GW1100 during SD stress did not cause deterioration of the emotional behavior. Furthermore, GW1100-treated SD-mice showed strong tendency of emotional dysfunction after paw incision.Our findings indicate that the dysfunction of fatty acids-GPR40/FFAR1 signaling in the brain underlying stress condition might be related to the development of chronic pain.