Aprepitant Inhibits JNK and p38/MAPK to Attenuate Inflammation and Suppresses Inflammatory Pain.
Aprepitant Inhibits JNK and p38/MAPK to Attenuate Inflammation and Suppresses Inflammatory Pain.
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阿瑞吡坦抑制 JNK 和 p38/MAPK 以减轻炎症并抑制炎症疼痛
DOI：
10.3389/fphar.2021.811584
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发表时间：
2021
影响因子：
5.6
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Yang Y;Zhou W;Xu X;Ge X;Wang F;Zhang GQ;Miao L;Deng X
P物质通过作用于NK-1R（检测有害刺激的特殊感觉神经元）参与疼痛的发病机制。阿瑞吡坦是一种NK-1R拮抗剂，被广泛用于治疗化疗引起的恶心和呕吐。本研究通过lps刺激BV-2小胶质细胞系和炎性疼痛动物模型，探讨阿瑞吡坦对炎性疼痛的镇痛作用及其机制。采用全细胞膜片钳法记录DRG神经元的兴奋性。采用HE染色法观察大鼠足部炎症组织的形态学变化。采用实时定量PCR和酶联免疫吸附法检测细胞因子的表达变化。免疫荧光和western blotting检测小胶质细胞活化和MAPK。阿瑞吡坦治疗显著抑制DRG神经元的兴奋性。与福尔马林组相比，阿瑞吡坦组大鼠疼痛行为和足部组织炎症损伤明显减轻。阿瑞吡坦在体内和体外均能显著抑制小胶质细胞的活化、JNK和p38 MAPK的磷酸化以及MCP-1、TNF-α、IL-6和IL-1β mRNA和蛋白的表达。阿瑞吡坦处理BV-2细胞后，lps诱导的NF-κBp65过易位被下调。本研究提示阿瑞吡坦通过抑制JNK和p38的磷酸化以及抑制NF-κB信号通路来减轻小鼠炎症性疼痛。
Substance P contributes to the pathogenesis of pain by acting on NK-1R, specialized sensory neurons that detect noxious stimuli. Aprepitant, an antagonist of NK-1R, is widely used to treat chemotherapy-induced nausea and vomiting. In this study, we used LPS-stimulated BV-2 microglia cell line and animal models of inflammatory pain to explore the analgesic effect of aprepitant on inflammatory pain and its underlying mechanism. The excitability of DRG neurons were measured using whole-cell patch-clamp recordings. The behavioral tests were measured and the morphological changes on inflamed paw sections were determined by HE staining. Changes in the expressions of cytokine were measured by using real-time quantitative PCR analysis and ELISA method. Immunofluorescence and western blotting were used to detect the microglia activation and MAPK. Aprepitant treatment significantly inhibited the excitability of DRG neurons. The pain behavior and the paw tissues inflammatory damage were significantly relived after the administration of aprepitant compared to formalin group. Aprepitant significantly suppressed the activation of microglia, phosphorylation of JNK and p38 MAPK, as well as the mRNA and protein expressions of MCP-1, TNF-α, IL-6, and IL-1β, in vivo and in vitro. The LPS-induced over-translocation into nucleus of NF-κBp65 was down-regulated following aprepitant treatment in BV-2 cells. The present study suggests that aprepitant attenuates inflammatory pain in mice via suppressing the phosphorylation of JNK and p38, and inhibiting the NF-κB signaling pathway.
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影响因子：
9.8
作者：
Chizh, B. A.;Goehring, M.;Koppert, W.
通讯作者：
Koppert, W.
影响因子：
4.3
作者：
Alam, Md Badrul;Ju, Mi-Kyoung;Lee, Sang Han
通讯作者：
Lee, Sang Han
影响因子：
38.3
作者：
Ramírez-García PD;Retamal JS;Shenoy P;Imlach W;Sykes M;Truong N;Constandil L;Pelissier T;Nowell CJ;Khor SY;Layani LM;Lumb C;Poole DP;Lieu T;Stewart GD;Mai QN;Jensen DD;Latorre R;Scheff NN;Schmidt BL;Quinn JF;Whittaker MR;Veldhuis NA;Davis TP;Bunnett NW
通讯作者：
Bunnett NW
影响因子：
4.9
作者：
Bang JS;Oh DH;Choi HM;Sur BJ;Lim SJ;Kim JY;Yang HI;Yoo MC;Hahm DH;Kim KS
通讯作者：
Kim KS
影响因子：
7
作者：
Ogawa, S.;Awaga, Y.;Takamatsu, H.
通讯作者：
Takamatsu, H.