Betaine Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Inhibiting KIF17-Mediated Nociception,ACS Chemical Neuroscience

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Betaine Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Inhibiting KIF17-Mediated Nociception
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2022-11-11 , DOI: 10.1021/acschemneuro.2c00380
Vineeta Tiwari ₁ , Siva Hemalatha ₁

Affiliation

Kinesin superfamily proteins transport a diverse range of cargo, including excitatory receptors to the dendrite and axon of a neuron via retrograde and anterograde fashions along microtubules, causing central sensitization and neuropathic pain. In this study, we have performed in silico molecular dynamics simulation to delineate the dynamic interaction of betaine with KIF17, a kinesin protein, known to be involved in neuropathic pain. The results from the molecular dynamics study suggest that the betaine–KIF17 complex is stabilized through hydrogen bonding, polar interactions, and water bridges. Findings from in vivo studies suggest a significant increase in pain hypersensitivity, oxido-nitrosative stress, and KIF17 overexpression in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of nerve-injured rats, which was significantly attenuated on treatment with betaine. Betaine treatment also restored the increased NR2B expressions and levels of proinflammatory cytokines and neuropeptides in the DRG and spinal cord of nerve-injured rats. Findings from the current study suggest that betaine attenuates neuropathic pain in rats by inhibiting KIF17-NR2B-mediated neuroinflammatory signaling.

中文翻译：

甜菜碱通过抑制 KIF17 介导的伤害感受减轻大鼠慢性压迫性损伤引起的神经性疼痛

驱动蛋白超家族蛋白通过沿着微管的逆行和顺行方式将包括兴奋性受体在内的各种货物运输到神经元的树突和轴突，从而引起中枢敏化和神经性疼痛。在这项研究中，我们进行了计算机分子动力学模拟，以描述甜菜碱与 KIF17 的动态相互作用，KIF17 是一种驱动蛋白，已知与神经性疼痛有关。分子动力学研究的结果表明，甜菜碱-KIF17 复合物通过氢键、极性相互作用和水桥得到稳定。来自体内的发现研究表明，神经损伤大鼠的坐骨神经、背根神经节 (DRG) 和脊髓中的疼痛超敏反应、氧化亚硝化应激和 KIF17 过表达显着增加，甜菜碱治疗后显着减弱。甜菜碱治疗还恢复了神经损伤大鼠的背根神经节和脊髓中增加的 NR2B 表达和促炎细胞因子和神经肽的水平。当前研究的结果表明，甜菜碱通过抑制 KIF17-NR2B 介导的神经炎症信号传导来减轻大鼠的神经性疼痛。

更新日期：2022-11-11

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