Ortiz Mario I, Cariño-Cortés Raquel, Muñoz-Pérez Víctor M, Medina-Solís Carlo Eduardo, Castañeda-Hernández Gilberto
Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico.
Área Académica de Odontología del Instituto de Ciencias de la Salud de la Universidad Autónoma del Estado de Hidalgo, San Agustín Tlaxiaca, Hidalgo, Mexico.
Can J Physiol Pharmacol. 2022 Apr;100(4):306-313. doi: 10.1139/cjpp-2021-0458. Epub 2021 Nov 26.
The objective of the present study was to scrutinize the effect of nitric oxide (NO), cyclic GMP (cGMP), potassium channel blockers, and metformin on the citral-produced peripheral antinociception. The rat paw 1% formalin test was used to assess nociception and antinociception. Rats were treated with local peripheral administration of citral (10-100 µg/paw). The antinociception of citral (100 µg/paw) was evaluated with and without the local pretreatment of naloxone, NG-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor), metformin, opioid receptors antagonists, and K channel blockers. Injection of citral in the rat paw significantly decreased the nociceptive effect of formalin administration during the two phases of the test. Local pretreatment of the paws with L-NAME and ODQ did not reduced the citral-induced antinociception. Glipizide or glibenclamide (K6.1-2; ATP-sensitive K channel blockers), tetraethylammonium or 4-aminopyridine (K; voltage-gated K channel blockers), charybdotoxin (K1.1; big conductance calcium-activated K channel blocker), apamin (K2.1-3; small conductance Ca-activated K channel antagonist), or metformin, but not the opioid antagonists, reduced the antinociception of citral. Citral produced peripheral antinociception during both phases of the formalin test. These effects were due to the activation of K channels and a biguanide-dependent mechanism.
本研究的目的是仔细研究一氧化氮（NO）、环磷酸鸟苷（cGMP）、钾通道阻滞剂和二甲双胍对柠檬醛产生的外周抗伤害感受的影响。采用大鼠足跖1%福尔马林试验来评估伤害感受和抗伤害感受。大鼠通过局部外周给予柠檬醛（10 - 100μg/足）进行处理。在有或没有预先局部给予纳洛酮、NG - L - 硝基精氨酸甲酯（L - NAME，一种NO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）、二甲双胍、阿片受体拮抗剂和钾通道阻滞剂的情况下，评估柠檬醛（100μg/足）的抗伤害感受作用。在试验的两个阶段，向大鼠足跖注射柠檬醛显著降低了福尔马林给药的伤害感受作用。用L - NAME和ODQ对足跖进行局部预处理并未降低柠檬醛诱导的抗伤害感受作用。格列吡嗪或格列本脲（K6.1 - 2；ATP敏感性钾通道阻滞剂）、四乙铵或4 - 氨基吡啶（K；电压门控钾通道阻滞剂）、蝎毒素（K1.1；大电导钙激活钾通道阻滞剂）、蜂毒明肽（K2.1 - 3；小电导钙激活钾通道拮抗剂）或二甲双胍，但不是阿片拮抗剂，降低了柠檬醛的抗伤害感受作用。在福尔马林试验的两个阶段，柠檬醛均产生外周抗伤害感受作用。这些作用归因于钾通道的激活和一种双胍依赖性机制。
