牛乳铁蛋白长期给药对神经病理性疼痛的影响：涉及阿片受体、一氧化氮和 TNF-α。
Effect of prolonged administration of bovine lactoferrin in neuropathic pain: involvement of opioid receptors, nitric oxide and TNF-alpha.
机构信息
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.
出版信息
Life Sci. 2010 Feb 13;86(7-8):251-9. doi: 10.1016/j.lfs.2009.12.007. Epub 2010 Jan 4.
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 effect.
MAIN 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 200mg/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 100mg/kg and nNOS expression at 100mg/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.
目的
本研究旨在探讨牛乳铁蛋白（bLF）长期给药对神经病理性疼痛大鼠模型中痛觉过敏和感觉异常的影响，并确定 c-Fos、TNF-α、一氧化氮和阿片能系统在此作用中的参与情况。
主要方法
通过对右侧坐骨神经的松结扎在大鼠中诱导神经病理性疼痛，并通过测量机械和热痛觉过敏和感觉异常的测试进行评估。bLF（50、100 和 200mg/kg）单独或与阿片能拮抗剂联合腹腔内给药给患有神经病理性疼痛的大鼠。在大鼠的腰椎脊髓中进行 c-Fos 和 NADPH-d 免疫细胞化学和 TNF-α、iNOS 和 nNOS 的 Western 印迹分析。通过 ELISA 测定血浆 TNF-α 水平。
主要发现
bLF 的长期（而非单次）给药在神经病理性大鼠中产生抗痛觉过敏和抗感觉异常作用。阿片能拮抗剂的预处理显著降低了这种作用。bLF 的长期给药可降低神经病理性大鼠腰椎脊髓中 c-Fos 和 NADPH-d 免疫反应性以及 TNF-α 和 iNOS 的表达（在 50 和 100mg/kg 时）和 nNOS 的表达（在 100mg/kg 时）。bLF 治疗后血浆 TNF-α 水平保持不变。
意义
bLF 的长期给药在神经病理性大鼠中产生抗痛觉过敏和抗感觉异常作用；腰椎脊髓中 TNF-α 和 iNOS 表达的下调以及阿片能系统的增强可能有助于这种作用。
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