School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Research Center for Integrative Medicine of Guangzhou University of Chinese Medicine, Key Laboratory of Chinese Medicine Pathogenesis and Therapy Research, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong. P.R. China.
Curr Neuropharmacol. 2023;21(11):2343-2361. doi: 10.2174/1570159X21666230802144940.
Brachial plexus avulsion (BPA) animally involves the separation of spinal nerve roots themselves and the correlative spinal cord segment, leading to formidable neuropathic pain of the upper limb.
The right seventh cervical (C7) ventral and dorsal roots were avulsed to establish a neuropathic pain model in rats. After operation, rats were treated with quercetin (QCN) by intragastric administration for 1 week. The effects of QCN were evaluated using mechanical allodynia tests and biochemical assay kits.
QCN treatment significantly attenuated the avulsion-provoked mechanical allodynia, elevated the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and total antioxidant capacity (TAC) in the C7 spinal dorsal horn. In addition, QCN administration inhibited the activations of macrophages, microglia and astrocytes in the C6 dorsal root ganglion (DRG) and C6-8 spinal dorsal horn, as well as attenuated the release of purinergic 2X (P2X) receptors in C6 DRG. The molecular mechanism underlying the above alterations was found to be related to the suppression of the PKC/MAPK/NOX signal pathway. To further study the anti-oxidative effects of QCN, we applied QCN on the HO-induced BV-2 cells , and the results attested that QCN significantly ameliorated the HO-induced ROS production in BV-2 cells, inhibited the HO-induced activation of PKC/MAPK/NOX pathway.
Our study for the first time provided evidence that QCN was able to attenuate pain hypersensitivity following the C7 spinal root avulsion in rats, and the molecular mechanisms involve the reduction of both neuro-inflammatory infiltration and oxidative stress via suppression of P2X receptors and inhibition of the activation of PKC/MAPK/NOX pathway. The results indicate that QCN is a natural compound with great promise worthy of further development into a novel therapeutic method for the treatment of BPA-induced neuropathic pain.
臂丛神经撕脱（BPA）动物模型涉及脊神经根本身和相关脊髓节段的分离，导致上肢严重的神经性疼痛。
第七颈椎（C7）腹侧和背根撕脱，建立大鼠神经性疼痛模型。手术后，用槲皮素（QCN）灌胃治疗 1 周。用机械性痛觉过敏试验和生化试剂盒评价 QCN 的作用。
QCN 治疗显著减轻撕脱引起的机械性痛觉过敏，提高 C7 脊髓背角过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和总抗氧化能力（TAC）水平。此外，QCN 给药抑制 C6 背根神经节（DRG）和 C6-8 脊髓背角中巨噬细胞、小胶质细胞和星形胶质细胞的激活，并减轻 C6 DRG 嘌呤能 2X（P2X）受体的释放。上述变化的分子机制与 PKC/MAPK/NOX 信号通路的抑制有关。为了进一步研究 QCN 的抗氧化作用，我们将 QCN 应用于 HO 诱导的 BV-2 细胞，结果表明 QCN 显著改善了 HO 诱导的 BV-2 细胞中 ROS 的产生，抑制了 HO 诱导的 PKC/MAPK/NOX 通路的激活。
我们的研究首次提供了证据，表明 QCN 能够减轻大鼠 C7 脊髓根撕脱后的痛觉过敏，其分子机制涉及通过减少神经炎症浸润和氧化应激来减少 P2X 受体的减少和抑制 PKC/MAPK/NOX 通路的激活。结果表明，QCN 是一种很有前途的天然化合物，值得进一步开发为治疗 BPA 诱导的神经性疼痛的新疗法。
