Rocha-González Héctor I, Meneses Alfredo, Carlton Susan M, Granados-Soto Vinicio
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, D.F., Mexico.
Pain. 2005 Sep;117(1-2):182-92. doi: 10.1016/j.pain.2005.06.011.
The possible pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test was assessed. Local administration of 5-HT7 (SB-269970, 2.5-77.1 nmol/paw), but not 5-HT(1A) (WAY-100635, 1-60 nmol/paw), receptor antagonist significantly reduced formalin-induced flinching. Local 5-hydroxytryptamine (5-HT, 3-100 nmol/paw) or 5-carboxamidotryptamine (5-CT, 0.3-3 nmol/paw) (a 5-HT7/1A receptor agonist) augmented, in a dose-dependent manner, 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of 5-HT or 5-CT was significantly reduced by SB-269970 (25 and 77.1 nmol/paw), but not by WAY-100635 (10 nmol/paw). 5-HT7 receptors were observed in myelinated and unmyelinated axons of the digital nerves in rat hindpaw. Intrathecal SB-269970 (2.5-77.1 nmol/rat) or WAY-100635 (1-50 nmol/rat) did not modify 1% formalin-induced nociceptive behavior. Spinal 5-HT (25-200 nmol/rat) significantly reduced formalin-induced flinching behavior during phase 2. At lower doses (0.1-3 nmol/rat) intrathecal 5-CT dose-dependently increased flinching during phase 2. In contrast, higher doses (10-30 nmol/rat) of 5-CT reduced formalin-induced nociceptive behavior during both phases. The spinal pronociceptive effect of 5-CT was reduced by SB-269970 (7.7-77 nmol/rat), but not by WAY-100635 (10 nmol/rat). In addition, the spinal antinociceptive effect of 5-CT was partially reversed by WAY-100635 (10 nmol/rat). The spinal antinociceptive effect of 5-HT was unaffected either by SB-269970 (77 nmol/rat) or WAY-100635 (10 nmol/rat). Data suggest that 5-HT7, but not 5-HT1A, receptors play a pronociceptive role in peripheral and spinal sites in the rat formalin test.
评估了外周和脊髓5-HT7受体在福尔马林试验中可能的促伤害感受作用。局部给予5-HT7受体拮抗剂（SB-269970，2.5 - 77.1 nmol/爪）可显著降低福尔马林诱导的退缩反应，而给予5-HT(1A)受体拮抗剂（WAY-100635，1 - 60 nmol/爪）则无此作用。局部给予5-羟色胺（5-HT，3 - 100 nmol/爪）或5-羧基胺基色胺（5-CT，0.3 - 3 nmol/爪）（一种5-HT7/1A受体激动剂）可剂量依赖性地增强0.5%福尔马林诱导的伤害感受行为。SB-269970（25和77.1 nmol/爪）可显著降低5-HT或5-CT的局部促伤害感受作用，而WAY-100635（10 nmol/爪）则无此作用。在大鼠后爪趾神经的有髓和无髓轴突中观察到了5-HT7受体。鞘内注射SB-269970（2.5 - 77.1 nmol/大鼠）或WAY-100635（1 - 50 nmol/大鼠）并未改变1%福尔马林诱导的伤害感受行为。脊髓注射5-HT（25 - 200 nmol/大鼠）可显著降低第二阶段福尔马林诱导的退缩行为。鞘内注射较低剂量（0.1 - 3 nmol/大鼠）的5-CT可剂量依赖性地增加第二阶段的退缩反应。相反，较高剂量（10 - 30 nmol/大鼠）的5-CT可降低两个阶段福尔马林诱导的伤害感受行为。SB-269970（7.7 - 77 nmol/大鼠）可降低5-CT的脊髓促伤害感受作用，而WAY-100635（10 nmol/大鼠）则无此作用。此外，WAY-100635（10 nmol/大鼠）可部分逆转5-CT的脊髓抗伤害感受作用。5-HT的脊髓抗伤害感受作用不受SB-269970（77 nmol/大鼠）或WAY-100635（10 nmol/大鼠）的影响。数据表明，在大鼠福尔马林试验中，5-HT7受体而非5-HT1A受体在周围和脊髓部位发挥促伤害感受作用。
