School of Basic Medical Sciences and Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
School of Clinical Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
Mol Med Rep. 2020 Aug;22(2):957-963. doi: 10.3892/mmr.2020.11157. Epub 2020 May 18.
Mechanical allodynia, which develops in patients of diabetes mellitus as a neuropathic manifestation, remains without an effective treatment. The aim of the present study was to investigate the effects and potential mechanisms underlying resveratrol (RES) in a rat model of streptozocin (STZ)‑induced diabetic mechanical allodynia (DMA). The rat model of DMA was established by the administration of an intraperitoneal injection of STZ. From day 8 post‑STZ injection, rats were administered with an intragastric injection of various doses of RES for 14 consecutive days. The von Frey filaments were applied to detect the paw withdrawal threshold and evaluate the analgesic effects of RES. Based on the dose‑effect curve, the ED50 of RES was calculated. Immunofluorescence staining and western blotting were performed to detect the expression of purinergic receptor P2X3 (P2X3R) in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) following RESED50 treatment. The results indicated that RES significantly alleviated mechanical allodynia in DMA model rats in a dose‑dependent manner. Compared with the control group, the expression of P2X3R in DRG neurons and SDH terminals was markedly decreased following the administration of RESED50 (P<0.05). Collectively, the results indicated that RES displayed a dose‑dependent analgesic effect on DMA model rats. Furthermore, P2X3R expression downregulation in the DRG and SDH may be a mechanism underlying the analgesic effects of RES on DMA‑related behaviors.
机械性痛觉过敏是糖尿病患者的一种神经病理性表现,目前尚无有效的治疗方法。本研究旨在探讨白藜芦醇(RES)在链脲佐菌素(STZ)诱导的糖尿病机械性痛觉过敏(DMA)大鼠模型中的作用及其潜在机制。通过腹腔注射 STZ 建立 DMA 大鼠模型。自 STZ 注射后第 8 天起,大鼠连续 14 天给予不同剂量的 RES 灌胃。使用 von Frey 细丝检测大鼠的足底缩足阈值,以评估 RES 的镇痛效果。根据剂量-效应曲线,计算 RES 的 ED50。采用免疫荧光染色和 Western blot 检测 RESED50 处理后背根神经节(DRG)和脊髓背角(SDH)中嘌呤能受体 P2X3(P2X3R)的表达。结果表明,RES 可显著减轻 DMA 模型大鼠的机械性痛觉过敏,且呈剂量依赖性。与对照组相比,RES 处理后 DRG 神经元和 SDH 末梢的 P2X3R 表达明显降低(P<0.05)。综上所述,RES 对 DMA 模型大鼠具有剂量依赖性镇痛作用。此外,DRG 和 SDH 中 P2X3R 表达下调可能是 RES 缓解 DMA 相关行为的镇痛作用机制。