Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Fundam Clin Pharmacol. 2023 Aug;37(4):779-785. doi: 10.1111/fcp.12880. Epub 2023 Feb 27.
Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.
神经病理性疼痛是最严重的慢性疼痛类型之一，尽管医学科学不断进步。亚精胺（SPD）是一种天然多胺，在诱导自噬和减少氧化应激等多种细胞过程中发挥广泛作用。本研究旨在探讨 SPD 对慢性缩窄性损伤（CCI）模型神经病理性大鼠模型中氧化应激标志物和疼痛阈值的影响。将 18 只成年雄性大鼠分为三组：假手术组、CCI 组和 CCI+SPD 组。CCI 组和 CCI+SPD 组通过 CCI 模型诱导神经病变后，CCI+SPD 组给予 SPD（1mg/kg/天，口服）治疗 3 周。实验过程中进行了 4 次行为测试（von Frey、热板）。研究结束时，进行了电生理测试、前额叶皮质（PFC）、脊髓和坐骨神经的 H&E 染色和氧化应激测定。热板和 von Frey 试验中的疼痛阈值在 CCI 组明显低于假手术组，CCI+SPD 组的 SPD 治疗逆转了这种情况。此外，CCI 组的神经传导明显低于假手术组和 CCI+SPD 组（P<0.01，P<0.05）。CCI 组在 H&E 检测中显示出不同组织中的神经元变性和纤维化；还观察到组织中硝酸盐水平升高，超氧化物歧化酶（SOD）、谷胱甘肽（GPx）和过氧化氢酶水平降低。然而，SPD 治疗调节了病理变化和氧化应激生物标志物。总之，SPD 显示出降低神经病理性疼痛的有益作用。SPD 治疗减轻了氧化应激，并改善了体内 CCI 诱导的神经病理性疼痛模型中的组织学变化和行为测试。
