Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine.
Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine.
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Toll样受体4的抑制可减轻实验性偏头痛中急性硬脑膜炎症引起的痛觉过敏
DOI：
10.1177/1744806918754612
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Yu S
中科院分区：
文献类型：
--
作者：
Su M;Ran Y;He Z;Zhang M;Hu G;Tang W;Zhao D;Yu S
尽管伤害性敏化是偏头痛和偏头痛慢性化的重要病理生理过程，但其潜在机制仍不清楚。 Toll 样受体 4 (TLR4) 是一种模式识别分子，在神经性疼痛和吗啡耐受中发挥着关键作用。本研究探讨了 TLR4 通路的元件是否会导致大鼠硬脑膜炎症引起的痛觉过敏。通过灌输硬脑膜炎汤建立大鼠偏头痛模型。用TAK-242预处理的组用于抑制TLR4的激活。通过Western blot和免疫荧光检测三叉神经通路中TLR4及其下游分子的蛋白水平。还分析了活化的小胶质细胞和星形胶质细胞的表达。通过酶联免疫吸附测定法测量白细胞介素-1β、肿瘤坏死因子-α和脑源性神经营养因子的水平。急性炎症汤输注引起时间依赖性面部机械痛觉过敏，TAK-242预处理可阻断这种情况。炎症汤刺激增加了 TLR4 下游分子和白细胞介素 1 β 的产生。给予炎症汤后观察到更高水平的小胶质细胞激活和脑源性神经营养因子释放，但 TAK-242 缓解了这一情况。这些数据表明，TLR4信号通路通过刺激促炎细胞因子的产生和激活小胶质细胞来促进急性炎症汤递送诱导的痛觉过敏。
Although nociceptive sensitisation is an important pathophysiological process in migraine and migraine chronification, its underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a pattern-recognition molecule, has a critical role in both neuropathic pain and morphine tolerance. The present study examined whether elements of the TLR4 pathway contribute to hyperalgesia induced by dural inflammation in rats. A rat model of migraine was established by infusing a dural inflammatory soup. A group pretreated with TAK-242 was used to inhibit the activation of TLR4. The protein levels of TLR4 and its downstream molecules in the trigeminal pathway were examined by Western blot and immunofluorescence. The expression of activated microglia and astrocytes was also analysed. Levels of interleukin-1 beta, tumour necrosis factor-alpha, and brain-derived neurotrophic factor were measured by enzyme-linked immunosorbent assay. Acute inflammatory soup infusion induced time-dependent facial mechanical hyperalgesia, which was blocked by TAK-242 pretreatment. The inflammatory soup stimulus increased the production of TLR4 downstream molecules and interleukin-1 beta. Higher levels of microglia activation and brain-derived neurotrophic factor release were observed following the administration of the inflammatory soup but were alleviated by TAK-242. These data suggest that the TLR4 signalling pathway promotes hyperalgesia induced by acute inflammatory soup delivery by stimulating the production of proinflammatory cytokines and activating microglia.
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影响因子：
9.3
作者：
Zhu HT;Bian C;Yuan JC;Chu WH;Xiang X;Chen F;Wang CS;Feng H;Lin JK
通讯作者：
Lin JK
影响因子：
6.2
作者：
Bettoni, Isabella;Comelli, Francesca;Costa, Barbara
通讯作者：
Costa, Barbara
影响因子：
1.7
作者：
Malhotra R
通讯作者：
Malhotra R
影响因子：
11.2
作者：
Edelmayer, Rebecca M.;Vanderah, Todd W.;Majuta, Lisa;Zhang, En-Tan;Fioravanti, Beatriz;De Felice, Milena;Chichorro, Juliana G.;Ossipov, Michael H.;King, Tamara;Lai, Josephine;Kori, Shashi H.;Nelsen, Andrew C.;Cannon, Keri E.;Heinricher, Mary M.;Porreca, Frank
通讯作者：
Porreca, Frank
影响因子：
7.4
作者：
Noseda R;Burstein R
通讯作者：
Burstein R