Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice.
Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice.
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DOI：
10.1371/journal.pone.0180610
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tokuyama S
中科院分区：
文献类型：
--
作者：
Nakamoto K;Aizawa F;Miyagi K;Yamashita T;Mankura M;Koyama Y;Kasuya F;Hirasawa A;Kurihara T;Miyata A;Tokuyama S
我们之前的研究表明，G蛋白偶联受体40/游离脂肪酸受体1 （GPR40/FFAR1）信号的激活调节了疼痛的下降抑制。在这项研究中，我们研究了脂肪酸- gpr40 /FFAR1信号在急性到慢性疼痛转变中的作用。我们使用GPR40/ ffar1敲除（GPR40KO）小鼠和野生型（WT）小鼠。行足底切口，分别用von Frey纤维试验和足底试验评估机械异常性痛和热痛感。采用免疫组化方法定位GPR40/FFAR1，液相色谱-串联质谱法分析下丘脑游离脂肪酸水平。重复给药GW1100 （GPR40/FFAR1拮抗剂）会加重切口引起的机械异常痛，并显著增加小鼠在低阈触摸刺激后脊髓中磷酸化的细胞外信号调节激酶的水平。GPR40/FFAR1激动剂长链游离脂肪酸，如二十二碳六烯酸、油酸和棕榈酸酯，在手术后2天下丘脑的水平与假手术组相比显著增加。此外，与WT小鼠相比，GPR40KO小鼠的切口引起的机械异常性疼痛加重，而足底试验的反应没有改变。这些发现提示GPR40/FFAR1信号通路的功能障碍改变了内源性疼痛控制系统，这种功能障碍可能与慢性疼痛的发生有关。
We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively. Immunohistochemistry was used to localize GPR40/FFAR1, and the levels of free fatty acids in the hypothalamus were analyzed with liquid chromatography-tandem mass spectrometry. The repeated administration of GW1100, a GPR40/FFAR1 antagonist, exacerbated the incision-induced mechanical allodynia and significantly increased the levels of phosphorylated extracellular signal-regulated kinase in the spinal cord after low-threshold touch stimulation in the mice compared to vehicle-treated mice. The levels of long-chain free fatty acids, such as docosahexaenoic acid, oleic acid, and palmitate, which are GPR40/FFAR1 agonists, were significantly increased in the hypothalamus two days after the surgery compared to levels in the sham group. Furthermore, the incision-induced mechanical allodynia was exacerbated in the GPR40KO mice compared to the WT mice, while the response in the plantar test was not changed. These findings suggested that dysfunction of the GPR40/FFAR1 signaling pathway altered the endogenous pain control system and that this dysfunction might be associated with the development of chronic pain.
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影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
3.5
作者：
Ma, Dexuan;Lu, Li;Yamashima, Tetsurnori
通讯作者：
Yamashima, Tetsurnori
影响因子：
4.7
作者：
Gao YJ;Ji RR
通讯作者：
Ji RR
DOI：
10.1111/j.1476-5381.1957.tb01354.x
发表时间：
1957-01-01
期刊：
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子：
--
作者：
HALEY, TJ;MCCORMICK, WG
通讯作者：
MCCORMICK, WG
影响因子：
8.8
作者：
Pogatzki, EM;Raja, SN
通讯作者：
Raja, SN