Lin Yuchao, Chen Kexin, Zhao Lei, Zhao Ming, Liu Yuanyuan, Li Yu
Department of Anesthesiology and Pain, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Department of Anesthesiology and Pain, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Arch Biochem Biophys. 2025 Oct;772:110572. doi: 10.1016/j.abb.2025.110572. Epub 2025 Jul 29.
This study aimed to investigate the effects of Dexmedetomidine (Dex) on oxaliplatin-induced neuropathic pain and its underlying mechanisms.
A murine model of oxaliplatin-induced neuropathic pain was established using intraperitoneal injections of oxaliplatin. Dex was administered at different doses, and behavioral tests were performed to assess pain. Spinal cord tissues were analyzed for inflammatory cytokines, oxidative stress markers, and key signaling molecules related to the toll-like receptor 4 (TLR4)/nuclear factor kappa B using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. In addition, in vitro experiments were conducted using TNF-α-stimulated C6 glial cells to further assess the anti-inflammatory effects of Dex.
Dex significantly alleviated oxaliplatin-induced neuropathic pain, as shown by an increase in paw withdrawal thresholds and a marked reduction in spontaneous flinching. Molecular analyses further demonstrated that Dex treatment reduced interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) expression, as well as malondialdehyde (MDA) and cyclooxygenase-2 (COX2) in the spinal cord. Concurrently, there was a notable enhancement in the activity of Manganese superoxide dismutase (Mn-SOD) and glutathione (GSH), suggesting improved antioxidative defense. Additionally, Dex reduced spinal inflammation and oxidative stress by downregulating TLR4 expression and inhibiting NF-κB activation. Consistent with these findings, Dex also suppressed NF-κB phosphorylation and cytokine expression in TNF-α-treated C6 cells in vitro.
Dex significantly reduced oxaliplatin-induced neuropathic pain by downregulating TLR4 expression and inhibiting NF-κB activation.
本研究旨在探讨右美托咪定（Dex）对奥沙利铂诱导的神经性疼痛的影响及其潜在机制。
通过腹腔注射奥沙利铂建立奥沙利铂诱导的神经性疼痛小鼠模型。给予不同剂量的Dex，并进行行为测试以评估疼痛。使用定量实时聚合酶链反应（qRT-PCR）、蛋白质印迹法和免疫组织化学分析脊髓组织中的炎性细胞因子、氧化应激标志物以及与Toll样受体4（TLR4）/核因子κB相关的关键信号分子。此外，使用肿瘤坏死因子-α（TNF-α）刺激的C6神经胶质细胞进行体外实验，以进一步评估Dex的抗炎作用。
Dex显著减轻了奥沙利铂诱导的神经性疼痛，表现为爪部撤离阈值升高和自发抽搐明显减少。分子分析进一步表明，Dex治疗降低了脊髓中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达，以及丙二醛（MDA）和环氧化酶-2（COX2）的水平。同时，锰超氧化物歧化酶（Mn-SOD）和谷胱甘肽（GSH）的活性显著增强，表明抗氧化防御能力提高。此外，Dex通过下调TLR4表达和抑制NF-κB激活减轻了脊髓炎症和氧化应激。与这些发现一致，Dex在体外也抑制了TNF-α处理的C6细胞中NF-κB的磷酸化和细胞因子表达。
Dex通过下调TLR4表达和抑制NF-κB激活，显著减轻了奥沙利铂诱导的神经性疼痛。
