Nascimento Carlos G O, Branco Luiz G S
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Eur J Pharmacol. 2008 Feb 26;581(1-2):71-6. doi: 10.1016/j.ejphar.2007.11.036. Epub 2007 Nov 28.
The aim of the present study was to investigate the role of the spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase (sGC)-cGMP pathway in nociceptive response of rats to the formalin experimental nociceptive model. Animals were handled and adapted to the experimental environment for a few days before the formalin test was applied. For the formalin test 50 microl of a 1% formalin solution was injected subcutaneously in the dorsal surface of the right hind paw. Following injections, animals were observed for 1 h and flinching behavior was measured as the nociceptive response. Thirty min before the test, rats were pretreated with intrathecal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control animals were treated with vehicles. We observed a significant increase in nociceptive response of rats treated with ZnDPBG, and a drastic reduction of flinching nociceptive behavioral response in the heme-lysinate treated animals. Furthermore, the HO pathway seems to act via cGMP, since methylene blue (a sGC inhibitor) prevented the reduction of flinching nociceptive behavioral response caused by heme-lysinate. These findings strongly indicate that the HO pathway plays a spinal antinociceptive role during the formalin test, acting via cGMP.
本研究的目的是探讨脊髓血红素加氧酶（HO）-一氧化碳（CO）-可溶性鸟苷酸环化酶（sGC）-环磷酸鸟苷（cGMP）通路在大鼠对福尔马林实验性伤害感受模型的伤害性反应中的作用。在进行福尔马林测试前，对动物进行了几天的处理并使其适应实验环境。在福尔马林测试中，将50微升1%的福尔马林溶液皮下注射到右后爪的背侧表面。注射后，观察动物1小时，并将退缩行为作为伤害性反应进行测量。在测试前30分钟，大鼠经鞘内注射HO抑制剂锌原卟啉IX二乙二醇（ZnDPBG）或已知可诱导HO通路的血红素赖氨酸盐进行预处理。对照动物用赋形剂处理。我们观察到用ZnDPBG处理的大鼠的伤害性反应显著增加，而用血红素赖氨酸盐处理的动物的退缩伤害性行为反应急剧减少。此外，HO通路似乎通过cGMP起作用，因为亚甲蓝（一种sGC抑制剂）阻止了血红素赖氨酸盐引起的退缩伤害性行为反应的减少。这些发现有力地表明，HO通路在福尔马林测试期间发挥脊髓抗伤害感受作用，通过cGMP起作用。
