The involvement of GPR40 ⁄ FFAR1 as a novel target of stress induced–chronic pain

Pain Research Pub Date : 2018-09-15 DOI:10.11154/PAIN.33.203
F. Aizawa, K. Nakamoto, S. Tokuyama
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Abstract

It has been accepted the fact that patients with chronic pain comorbid with depression or anxiety appeal profoundly severe pain condition more than healthful emotional condition. The critical treatment of chronic pain has not been appeared although noradrenergic and serotonergic neurons were discovered as a target of treatment such as depression or anxiety. Recently, the importance of function of the n–3 free fatty acids (FFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid is focused on the novel target of chronic pain. However, the mechanism has not been elucidated. The G–protein coupled receptor 40 ⁄ free fatty acid receptor 1 (GPR40 ⁄ FFAR1), a receptor of middle–long chain FFAs including DHA, distribute in the brain of human and rodents. We previously reported that the GPR40 ⁄ FFAR1 suppressed not only various pain stimuli via activation of endogenous pain regulation systems but also depression–like behavior. Our previous study demonstrated that the GPR40 ⁄ FFAR1 knock–out mice show the persistent of mecha nical allodynia after hind–paw incision. Furthermore, the GPR40 ⁄ FFAR1 knock–out mice show the abnormal emotional behaviors. Our results suggested that the GPR40 ⁄ FFAR1 has the potential of the novel therapeutic target of stress–induced chronic pain.
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GPR40 / FFAR1作为应激性慢性疼痛的新靶点
人们普遍认为,慢性疼痛伴抑郁或焦虑的患者对严重疼痛状态的吸引力大于健康的情绪状态。虽然去甲肾上腺素能和血清素能神经元被发现是治疗抑郁或焦虑等慢性疼痛的靶点,但对慢性疼痛的关键治疗尚未出现。近年来,n-3游离脂肪酸(FFAs)如二十二碳六烯酸(DHA)和二十碳五烯酸的功能被关注于慢性疼痛的新靶点。然而,其机制尚未阐明。g蛋白偶联受体40⁄游离脂肪酸受体1 (GPR40⁄FFAR1)是一种包括DHA在内的中长链脂肪酸受体,分布于人和啮齿类动物的大脑中。我们之前报道过GPR40 / FFAR1不仅通过激活内源性疼痛调节系统抑制各种疼痛刺激,而且还抑制抑郁样行为。我们前期的研究表明GPR40 / FFAR1基因敲除小鼠后爪切开后机械异常性疼痛持续存在。此外,GPR40 / FFAR1基因敲除小鼠表现出异常的情绪行为。我们的研究结果表明GPR40 / FFAR1有潜力成为应激性慢性疼痛的新治疗靶点。
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来源期刊
Pain Research
Pain Research CLINICAL NEUROLOGY-
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