Ortiz Mario I, Medina-Tato David A, Sarmiento-Heredia Denisse, Palma-Martínez Jazmín, Granados-Soto Vinicio
Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
Pharmacol Biochem Behav. 2006 Mar;83(3):420-7. doi: 10.1016/j.pbb.2006.03.002. Epub 2006 Apr 21.
The effect of modulators of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway on the local peripheral antinociceptive action induced by gabapentin was assessed in the rat 1% formalin test. Local peripheral administration of gabapentin produced a dose-dependent antinociception in the second phase of the test. Gabapentin-induced antinociception was due to a local action as its administration in the contralateral paw was ineffective. Local peripheral pretreatment of the paws with NG-L-nitro-arginine methyl ester (L-NAME, a nitric oxide synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) and KT-5823 (a protein kinase G inhibitor) dose-dependently reduced gabapentin-induced antinociception. Likewise, glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), 4-aminopyridine or tetraethylammonium (non-selective inward rectifier K+ channel inhibitors) or charybdotoxin (large-conductance Ca2+-activated-K+ channel blocker), but not apamin (small-conductance Ca2+-activated-K+ channel blocker) or naloxone (opioid receptor antagonist), reduced the antinociception induced by gabapentin. Our data suggest that gabapentin could activate the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in order to produce its peripheral antinociceptive effect in the rat 1% formalin test.
在大鼠1%福尔马林试验中，评估了一氧化氮-环磷酸鸟苷-蛋白激酶G-K⁺通道途径调节剂对加巴喷丁诱导的局部外周抗伤害感受作用的影响。在试验的第二阶段，局部外周给予加巴喷丁产生了剂量依赖性的抗伤害感受作用。加巴喷丁诱导的抗伤害感受作用是由于其局部作用，因为在对侧爪给药无效。用NG-L-硝基精氨酸甲酯（L-NAME，一种一氧化氮合成抑制剂）、1H-(1,2,4)-恶二唑并(4,2-a)喹喔啉-1-酮（ODQ，一种可溶性鸟苷酸环化酶抑制剂）和KT-5823（一种蛋白激酶G抑制剂）对爪进行局部外周预处理，剂量依赖性地降低了加巴喷丁诱导的抗伤害感受作用。同样，格列本脲或甲苯磺丁脲（ATP敏感性K⁺通道抑制剂）、4-氨基吡啶或四乙铵（非选择性内向整流K⁺通道抑制剂）或蝎毒素（大电导Ca²⁺激活K⁺通道阻滞剂），但不是蜂毒明肽（小电导Ca²⁺激活K⁺通道阻滞剂）或纳洛酮（阿片受体拮抗剂），降低了加巴喷丁诱导的抗伤害感受作用。我们的数据表明，在大鼠1%福尔马林试验中，加巴喷丁可能激活一氧化氮-环磷酸鸟苷-蛋白激酶G-K⁺通道途径，以产生其外周抗伤害感受作用。
