Involvement of the nitric oxide–cyclic GMP–protein kinase G–K⁺ channel pathway in the antihyperalgesic effects of bovine lactoferrin in a model of neuropathic pain

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• 作者：Jun Wang ; Li-Cai Zhang ; You-Wen Lv ; Yong Ji ; Xue-Jun Yan ; Jin-Pei Xue
• 关键词：Lactoferrin ; Neuropathic pain ; Nitric oxide ; Protein kinase G
• 刊名：Brain Research
• 出版年：2008
• 出版时间：13 May 2008
• 年：2008
• 卷：1209
• 期：Complete
• 页码：1-7
• 全文大小：286 K

文摘

The possible involvement of the nitric oxide (NO)–cyclic GMP (cGMP)–protein kinase G (PKG) pathway on bovine lactoferrin (BLF)-induced spinal antihyperalgesic activity was elucidated in sciatic nerve injured rats. Intrathecal BLF reduced thermal hyperalgesia in a dose-dependent manner. Pretreatment with N^G-l-nitro-arginine methyl ester (l-NAME, non-specific inhibitor of NO synthase), 7-nitroindazole (7-NI, neuronal NO synthase inhibitor), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl-cyclase inhibitor), (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2, 9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo-[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor) or glybenclamide (ATP-sensitive K⁺ channel blocker), but not N^G-d-nitro-arginine methyl ester (d-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH₂ (CTOP, selective μ-opioid receptor antagonist) or naloxone (nonselective opioid receptor antagonist) prevented BLF-induced antihyperalgesia. Data suggest that BLF-induced spinal antihyperalgesia could be due to activation of the NO–cGMP–PKG–K⁺ channel pathway and it is not mediated by μ-opioid receptor in a model of neuropathic pain.