BACKGROUND & AIMS:
:The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG)-K(+) channel pathway on melatonin-induced local antinociception was assessed during the second phase of the formalin test. The local peripheral ipsilateral, but not contralateral, administration of melatonin (150-600 microg/paw) produced a dose-related antinociception during both phases of the formalin test in rats. Moreover, local pretreatment with N(G)-L-nitro-arginine methyl ester (L-NAME, NO synthesis inhibitor, 10-100 microg/paw), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor, 5-50 microg/paw), (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, 50-500 ng/paw), glibenclamide (ATP-sensitive K(+) channel blocker, 5-50 microg/paw), apamin (small-conductance Ca(2+)-activated K(+) channel blocker, 0.1-1 microg/paw) or charybdotoxin (large- and intermediate-conductance Ca(2+)-activated K(+) channel blocker, 0.03-0.3 microg/paw), but not N(G)-D-nitro-arginine methyl ester (D-NAME, inactive isomer of L-NAME, 100 microg/paw) or vehicle, significantly prevented melatonin (300 microg/paw)-induced antinociception. Data suggest that melatonin-induced local peripheral antinociception during the second phase of the test could be due to activation of the NO-cyclic GMP-PKG-ATP-sensitive and Ca(2+)-activated K(+) channels pathway.
背景与目标:
: 在福尔马林试验的第二阶段评估了一氧化氮 (NO)-环状GMP-蛋白激酶G (PKG)-K () 通道途径对褪黑激素诱导的局部抗伤害感受的可能参与。在大鼠福尔马林试验的两个阶段,褪黑激素 (150-600 microg/paw) 的局部外周同侧而不是对侧施用产生了剂量相关的抗伤害感受。此外,用N(G)-L-硝基精氨酸甲酯 (L-NAME,NO合成抑制剂,10-100微G/paw),1H-(1,2,4)-恶二唑 (4,2-a)quinoxalin-1-one (ODQ,鸟苷酸环化酶抑制剂,5-50微克/爪),(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 [1,2,3-fg:3 ',2',1 '-kl] 吡咯 [3,4-i][1,6] benzodiazocine-10-carboxylic甲酯 (KT-5823,特异性PKG抑制剂,50-500 ng/paw),格列本脲 (ATP敏感的K(+) 通道阻滞剂,5-50 microg/paw),apamin (小电导Ca(2 +) 激活的K(+) 通道阻滞剂,0.1-1 microg/paw) 或charybdotoxin (大电导Ca(2 +) 激活的K(+) 通道阻滞剂,0.03-0.3 microg/paw),但不是N(G)-D-硝基精氨酸甲酯 (D-NAME,L-NAME的非活性异构体,100 microg/paw) 或媒介物,显著阻止了褪黑素 (300微克/爪) 诱导的抗伤害感受。数据表明,褪黑素在测试的第二阶段诱导的局部外周抗伤害感受可能是由于激活了非环GMP-PKG-ATP敏感和Ca(2 +) 激活的K(+) 通道途径。