Lu Ying-Yi, Tsai Hung-Pei, Tsai Tai-Hsin, Miao Hsiao-Chien, Zhang Zi-Hao, Wu Chieh-Hsin
Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.
Department of Post-Baccalaureate Medicine, School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan.
Mol Neurobiol. 2024 Mar;61(3):1714-1725. doi: 10.1007/s12035-023-03660-w. Epub 2023 Sep 29.
Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.
神经损伤后的神经性疼痛是一种复杂的病症，常常对生活产生负面影响且一直是个棘手的问题。改善疼痛管理具有重大意义且存在未被满足的需求。RTA 408（奥马韦洛酮）是一种具有有效抗炎特性的传统亚洲药物。因此，我们旨在研究RTA - 408对慢性缩窄性损伤（CCI）大鼠机械性异常性疼痛的治疗效果及其潜在机制。通过对大鼠坐骨神经（SN）进行CCI诱导神经性疼痛，并使用校准镊子测试来测量行为。通过蛋白质免疫印迹法评估Nrf - 2的激活、核因子κB（NF - κB）的磷酸化以及炎症反应。通过免疫荧光测定法检测凋亡神经元的数量和胶质细胞反应程度。RTA - 408对CCI大鼠具有镇痛作用。RTA - 408通过增加Nrf - 2表达并减少炎症反应（TNF - α/p - NF - κB/TSLP/STAT5）来减少神经元凋亡和胶质细胞激活。这些数据表明，RTA - 408是一种有潜力通过靶向TSLP/STAT5信号通路来减轻CCI后伤害性超敏反应的候选药物。
