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Quercetin Ameliorates CFA-Induced Chronic Inflammatory Hyperalgesia via Modulation of ROS-Mediated ERK1/2 Signaling and Inhibition of Spinal Glial Activation In Vivo.
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2020-08-19 , DOI: 10.1007/s12017-020-08609-z
Sanjay Kumar 1 , Manjula Vinayak 1
Affiliation  

Impact of reactive oxygen species (ROS) in development of hyperalgesia has recently motivated scientists to focus on ROS as novel target of anti-hyperalgesic interventions. Studies have indicated the usefulness of ROS scavengers and exogenous antioxidants as anti-nociceptive agents in animal models of neuropathic and inflammatory hyperalgesia. In present study, we suggest the anti-hyperalgesic potential of the dietary antioxidant quercetin on chronic inflammatory hyperalgesia induced by Complete Freund’s Adjuvant (CFA). Three doses of quercetin (25, 50 and 75 mg/kg body weight) for consecutive 7 days were used for the study. Thermal hyperalgesia was assessed by paw withdrawal latency (PWL) test and inflammation was checked in terms of changes in paw edema. The insight of molecular signaling during chronic hyperalgesia was analyzed by TNF-α–TNFR1–ERK1/2 pathway in relation to change in ROS level in DRG and spinal cord. CFA-induced hyperalgesia was confirmed by decreased PWL and increased c-Fos activity in dorsal horn of spinal cord, determined by immunohistochemical analysis. It was characterized with elevated level of ROS and TNF-α estimated by ELISA. The activation of ERK1/2 and NF-κB in DRG and spinal cord and over-expression of TNFR1 in DRG were analyzed by Western blotting. Up-regulation of Iba1 and GFAP indicates glial activation in spinal cord. Expression of GFAP and its co-localization with NF-κB were examined by immunofluorescence. All the molecular modulators of hyperalgesia were brought towards normal after quercetin treatment showing its anti-hyperalgesic activity, indicating that repeated quercetin treatment is able to alleviate chronic inflammatory hyperalgesia by attenuating TNF-α-TNFR1–ERK1/2 signaling pathway via modulation of ROS and by suppression of central sensitization via inhibition of spinal glial activation.



中文翻译:

槲皮素通过调节 ROS 介导的 ERK1/2 信号传导和抑制体内脊髓胶质激活,改善 CFA 诱导的慢性炎症性痛觉过敏。

活性氧 (ROS) 在痛觉过敏发展中的影响最近促使科学家们将 ROS 作为抗痛觉过敏干预的新目标。研究表明 ROS 清除剂和外源性抗氧化剂在神经性和炎症性痛觉过敏动物模型中作为抗伤害性药物的有用性。在目前的研究中,我们建议膳食抗氧化剂槲皮素对完全弗氏佐剂 (CFA) 诱导的慢性炎症性痛觉过敏的抗痛觉过敏潜力。该研究使用了连续 7 天的三剂槲皮素(25、50 和 75 毫克/千克体重)。通过缩爪潜伏期(PWL)测试评估热痛觉过敏,并根据爪水肿的变化检查炎症。通过 TNF-α-TNFR1-ERK1/2 通路分析慢性痛觉过敏过程中分子信号传导与背根神经节和脊髓中 ROS 水平变化的关系。通过免疫组织化学分析确定的脊髓背角 PWL 降低和 c-Fos 活性增加证实了 CFA 诱导的痛觉过敏。其特征在于通过ELISA估计的ROS和TNF-α水平升高。通过蛋白质印迹分析DRG和脊髓中ERK1/2和NF-κB的活化以及DRG中TNFR1的过表达。Iba1 和 GFAP 的上调表明脊髓中的神经胶质激活。通过免疫荧光检查GFAP的表达及其与NF-κB的共定位。槲皮素处理后所有痛觉过敏分子调节剂均恢复正常,显示其抗痛觉过敏活性,

更新日期:2020-08-19
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