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Effect of prolonged administration of bovine lactoferrin in neuropathic pain:Involvement of opioid receptors, nitric oxide and TNF-alpha

机译:长期服用牛乳铁蛋白在神经性疼痛中的作用:阿片受体,一氧化氮和TNF-α的参与

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Aims: This study aimed to investigate the effect of prolonged administration of bovine milk lactoferrin (bLF) on hyperalgesia and allodynia in a rat model of neuropathic pain and to determine the involvement of c-Fos, TNF-alpha, nitric oxide and opioidergic systems in this effectMain methods: Neuropathic pain was induced in rats by loose ligation of the right sciatic nerve and evaluated by tests measuring the mechanical and thermal hyperalgesia and allodynia. bLF (50, 100, and 200 mg/kg) alone or in combination with opioidergic antagonists were administered intraperitoneally to the rats with neuropathic pain. c-Fos and NADPH-d immunocytochemistry and Western blotting for TNF-alpha, iNOS and nNOS were performed in the lumbar spinal cord of rats. Plasma TNF-alpha levels were determined with ELISA. Key findings: Prolonged, but not single, administration of bLF produced antihyperalgesic and antiallodynic effects in neuropathic rats. Pretreatment with opioidergic antagonists significantly decreased this effect Prolonged administration of bLF decreased c-Fos and NADPH-d immunoreactivity and TNF-alpha and iNOS expressions at 50 and 100 mg/kg and nNOS expression at 100 mg/kg in the lumbar spinal cord of neuropathic rats. Plasma TNF-alpha levels remained unchanged after bLF treatment.Significance: Prolonged administration of bLF exerts antihyperalgesic and antiallodynic effect in neuropathic rats; down-regulation of both TNF-alpha and iNOS expressions and potentiation of opioidergic system in the lumbar spinal cord can contribute to this effect.
机译:目的:本研究旨在研究长期服用牛乳乳铁蛋白(bLF)对神经性疼痛大鼠模型中的痛觉过敏和异常性疼痛的影响,并确定c-Fos,TNF-α,一氧化氮和阿片类药物系统的参与主要方法:右坐骨神经松散结扎可诱发大鼠神经性疼痛,并通过测量机械和热痛觉过敏和异常性疼痛的测试进行评估。向患有神经性疼痛的大鼠腹膜内给予bLF(50、100和200 mg / kg)单独或与阿片体能拮抗剂联合使用。在大鼠腰脊髓中进行c-Fos和NADPH-d免疫细胞化学分析以及TNF-α,iNOS和nNOS的Western印迹分析。用ELISA测定血浆TNF-α水平。关键发现:长期(但不是一次性)给予bLF可以在神经性大鼠中产生抗痛觉过敏和抗痛觉过敏的作用。用去皮激素拮抗剂预处理可显着降低这种作用。长期服用bLF会降低神经病性腰椎脊髓的c-Fos和NADPH-d免疫反应性以及50和100 mg / kg时的TNF-alpha和iNOS表达以及100 mg / kg时的nNOS表达大鼠。 bLF治疗后血浆TNF-α水平保持不变。意义:长期服用bLF对神经病大鼠具有抗痛觉过敏和抗痛觉过敏的作用。 TNF-α和iNOS表达的下调以及腰椎脊髓阿片体能系统的增强都可能有助于这种作用。

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