Wang Jun, Zhang Li-Cai, Lv You-Wen, Ji Yong, Yan Xue-Jun, Xue Jin-Pei
Department of Anesthesiology, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China.
Brain Res. 2008 May 13;1209:1-7. doi: 10.1016/j.brainres.2008.03.004. Epub 2008 Mar 18.
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 NG-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 NG-D-nitro-arginine methyl ester (D-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2 (CTOP, selective mu-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 mu-opioid receptor in a model of neuropathic pain.
在坐骨神经损伤大鼠中，研究了一氧化氮（NO）-环磷酸鸟苷（cGMP）-蛋白激酶G（PKG）通路在牛乳铁蛋白（BLF）诱导的脊髓抗痛觉过敏活性中的可能作用。鞘内注射BLF以剂量依赖的方式减轻热痛觉过敏。用NG-L-硝基精氨酸甲酯（L-NAME，一氧化氮合酶的非特异性抑制剂）、7-硝基吲唑（7-NI，神经元型一氧化氮合酶抑制剂）、1H-[1,2,4]-恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，鸟苷酸环化酶抑制剂）、(9S,10R,12R)-2,3,9,10,11,12-六氢-10-甲氧基-2,9-二甲基-1-氧代-9,12-环氧-1H-二吲哚并-[1,2,3-fg:3',2',1'-kl]吡咯并[3,4-i][1,6]苯并二氮杂䓬-10-羧酸甲酯（KT-5823，特异性PKG抑制剂）或格列本脲（ATP敏感性钾通道阻滞剂）预处理，但用NG-D-硝基精氨酸甲酯（D-NAME，L-NAME的无活性对映体）、d-苯丙氨酸-半胱氨酸-酪氨酸-d-色氨酸-鸟氨酸-苏氨酸-NH2（CTOP，选择性μ-阿片受体拮抗剂）或纳洛酮（非选择性阿片受体拮抗剂）预处理不能阻止BLF诱导的抗痛觉过敏。数据表明，在神经性疼痛模型中，BLF诱导的脊髓抗痛觉过敏可能是由于NO-cGMP-PKG-K+通道通路的激活，且不是由μ-阿片受体介导的。
