Oyama T, Ueda M, Kuraishi Y, Akaike A, Satoh M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Neurosci Res. 1996 Jun;25(2):129-35. doi: 10.1016/0168-0102(96)01034-6.
To examine the role of the descending serotonergic system in the regulation of spinal nociceptive processing, the effects of serotonin (5-HT) and selective ligands for 5-HT receptor subtypes on persistent nociception were investigated. Formalin (5% formaldehyde) injected into the plantar region of the rat hindpaw induced two phases of aversive responses such as licking and biting. Intrathecal administration of selective 5-HT3 receptor antagonists, granisetron (0.1-100 pmol/rat) and ondansetron (1-1000 pmol/rat), reduced the second phase of the formalin-induced aversive responses without affecting the first one. The antinociceptive effect of granisetron (100 pmol/rat) was abolished when 5-HT was depleted from the lumbar cord by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT). In the 5,7-DHT-treated rats, intrathecal administration of 1-(m-chlorophenyl)-biguanide, a selective 5-HT3 receptor agonist, facilitated the aversive responses in the second phase whereas that of 8-OH-DPAT, a selective 5-HT1A receptor agonist, suppressed them. Intrathecal administration of 5-HT showed a dual effect on the second phase of the aversive responses in the 5,7-DHT-treated rats; 5-HT inhibited the aversive responses when administered at a low dose (0.1 nmol/rat) but facilitated them at a high dose (1 nmol/rat). In addition, the inhibitory and facilitatory effects of intrathecal 5-HT were blocked by its co-administration with NAN190, a 5-HT1A receptor antagonist, and granisetron, respectively. These results suggest that 5-HT suppresses formalin-induced nociception in the spinal cord via the 5-HT1A receptor and facilitates it via the 5-HT3 receptor.
为研究下行5-羟色胺能系统在脊髓伤害性信息处理调节中的作用，我们研究了5-羟色胺（5-HT）及5-HT受体亚型选择性配体对持续性伤害感受的影响。将福尔马林（5%甲醛）注射到大鼠后爪足底区域可诱发两个阶段的厌恶反应，如舔舐和咬噬。鞘内注射选择性5-HT3受体拮抗剂格拉司琼（0.1 - 100 pmol/大鼠）和昂丹司琼（1 - 1000 pmol/大鼠）可减轻福尔马林诱发厌恶反应的第二阶段，而不影响第一阶段。当用5,7-二羟色胺（5,7-DHT）预处理使腰髓中的5-HT耗竭时，格拉司琼（100 pmol/大鼠）的抗伤害感受作用消失。在5,7-DHT处理的大鼠中，鞘内注射选择性5-HT3受体激动剂1-(间氯苯基) - 双胍可促进第二阶段的厌恶反应，而选择性5-HT1A受体激动剂8-OH-DPAT则可抑制该反应。鞘内注射5-HT对5,7-DHT处理大鼠厌恶反应的第二阶段表现出双重作用；低剂量（0.1 nmol/大鼠）给药时5-HT抑制厌恶反应，高剂量（1 nmol/大鼠）给药时则促进该反应。此外，鞘内注射5-HT的抑制和促进作用分别被其与5-HT1A受体拮抗剂NAN190和格拉司琼共同给药所阻断。这些结果表明，5-HT通过5-HT1A受体抑制脊髓中福尔马林诱发的伤害感受，并通过5-HT3受体促进该反应。
