Yu Zhi, Liu Jiayu, Sun Le, Wang Yusheng, Meng Hongmei
Department of Otolaryngology, Bethune First Hospital of Jilin University, Changchun, China.
Department of Neurology, Bethune First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2021 Mar 8;11:602417. doi: 10.3389/fphar.2020.602417. eCollection 2020.
Neuropathic pain (NP) is one of the intractable complications of spinal cord injury (SCI), with poor prognosis and seriously affects the quality of life of patients. This study aims to determine the treatment effect and mechanism of multimodal therapies in a rat model of SCI-induced NP by combining treatment with the anti-inflammatory agent minocycline (MC) and botulinum toxin (BoNT). The combined utilization alleviated SCI-induced NP and reduced apoptosis, inflammation, and oxidative stress of SCI by activating SIRT1 and dampening pAKT, P53, and p-NF-KB. BoNT with a concentration of 0.1 nm and MC with a concentration of 20 uM were selected for the experiment in the primary microglia and astrocytes treated with LPS. It was found that the combination of BoNT and MC obviously inhibits the inflammatory response and oxidative stress of glial cells, and notably activates SIRT1 and restrains pAKT, P53, and p-NF-KB. Therefore, in the treatment of SCI-induced NP, the combination of BoNT and MC markedly improves the therapeutic effect of NP by promoting the SIRT1 expression, thereby inactivating NF-KB, P53, and PI3K/AKT signaling pathway, inhibiting inflammation and oxidative stress as well as relieving SCI-induced NP.
神经病理性疼痛（NP）是脊髓损伤（SCI）难以处理的并发症之一，预后较差，严重影响患者的生活质量。本研究旨在通过将抗炎药物米诺环素（MC）和肉毒杆菌毒素（BoNT）联合治疗，确定多模式疗法在SCI诱导的NP大鼠模型中的治疗效果和机制。联合应用通过激活SIRT1并抑制pAKT、P53和p-NF-κB，减轻了SCI诱导的NP，并减少了SCI的细胞凋亡、炎症和氧化应激。在经脂多糖处理的原代小胶质细胞和星形胶质细胞实验中，选择浓度为0.1 nM的BoNT和浓度为20 μM的MC。结果发现，BoNT和MC联合明显抑制胶质细胞的炎症反应和氧化应激，并显著激活SIRT1，抑制pAKT、P53和p-NF-κB。因此，在治疗SCI诱导的NP时，BoNT和MC联合通过促进SIRT1表达，从而使NF-κB、P53和PI3K/AKT信号通路失活，抑制炎症和氧化应激以及缓解SCI诱导的NP，显著提高了NP的治疗效果。
