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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Acetic acid- and phenyl-p-benzoquinone-induced overt pain-like behavior depends on spinal activation of MAP kinases, PI 3K and microglia in mice
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Acetic acid- and phenyl-p-benzoquinone-induced overt pain-like behavior depends on spinal activation of MAP kinases, PI 3K and microglia in mice

机译：乙酸和苯基对苯醌引起的明显疼痛样行为取决于小鼠中MAP激酶，PI 3K和小胶质细胞的脊髓活化

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The acetic acid and phenyl-p-benzoquinone are easy and fast screening models to access the activity of novel candidates as analgesic drugs and their mechanisms. These models induce a characteristic and quantifiable overt pain-like behavior described as writhing response or abdominal contortions. The knowledge of the mechanisms involved in the chosen model is a crucial step forward demonstrating the mechanisms that the candidate drug would inhibit because the mechanisms triggered in that model will be addressed. Herein, it was investigated the role of spinal mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated kinase), JNK (Jun N-terminal Kinase) and p38, PI 3K (phosphatidylinositol 3-kinase) and microglia in the writhing response induced by acetic acid and phenyl-p-benzoquinone, and flinch induced by formalin in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing response over 20 min. The nociceptive response in these models were significantly and in a dose-dependent manner reduced by intrathecal pre-treatment with ERK (PD98059), JNK (SB600125), p38 (SB202190) or PI 3K (wortmannin) inhibitors. Furthermore, the co-treatment with MAP kinase and PI 3K inhibitors, at doses that were ineffective as single treatment, significantly inhibited acetic acid- and phenyl-p-benzoquinone- induced nociception. The treatment with microglia inhibitors minocycline and fluorocitrate also diminished the nociceptive response. Similar results were obtained in the formalin test. Concluding, MAP kinases and PI 3K are important spinal signaling kinases in acetic acid and phenyl-p-benzoquinone models of overt pain-like behavior and there is also activation of spinal microglia indicating that it is also important to determine whether drugs tested in these models also modulate such spinal mechanisms.
机译：乙酸和苯基对苯醌是简便，快速的筛选模型，可作为镇痛药及其机制使用新型候选药物的活性。这些模型诱发了特征性和可量化的明显疼痛样行为，称为扭体反应或腹部扭曲。了解所选模型涉及的机制是向前迈出的关键一步，这将证明候选药物将抑制的机制，因为将解决该模型中触发的机制。在此，研究了脊髓丝裂原活化蛋白（MAP）激酶ERK（细胞外信号调节激酶），JNK（Jun N端激酶）和p38，PI 3K（磷脂酰肌醇3-激酶）和小胶质细胞在扭体中的作用乙酸和苯基-对-苯醌诱导的小鼠反应，以及福尔马林诱导的小鼠退缩。乙酸和苯基对苯醌在20分钟内引起明显的扭曲反应。在这些模型中，通过鞘内预处理ERK（PD98059），JNK（SB600125），p38（SB202190）或PI 3K（渥曼青霉素）抑制剂可显着并以剂量依赖性方式降低其伤害性反应。此外，以单次治疗无效的剂量与MAP激酶和PI 3K抑制剂共同治疗可显着抑制乙酸和苯基-对-苯醌醌诱导的伤害感受。小胶质细胞抑制剂米诺环素和氟柠檬酸的治疗也减少了伤害反应。在福尔马林测试中获得了相似的结果。结论是，MAP激酶和PI 3K是乙酸和明显疼痛样行为的苯基和对苯二醌模型中的重要脊髓信号激酶，并且脊髓小胶质细胞也存在激活，这表明确定在这些模型中测试的药物是否重要也很重要也可以调节这种脊柱机制。

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