Danzebrink R M, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Brain Res. 1991 Jan 4;538(1):64-75. doi: 10.1016/0006-8993(91)90377-8.
This study examined whether the antinociception produced following the intrathecal (i.t.) administration of serotonin (5-hydroxytryptamine, 5-HT) and other 5-HT receptor agonists in a model of visceral pain that utilizes colorectal distension (CRD) as the noxious visceral stimulus is mediated through interaction with spinal 5-HT1, 5-HT2, or 5-HT3 receptor subtypes. CRD in conscious rats reliably elicits two pseudaffective reflexes: a vigorous pressor response and a visceromotor response. Antinociception is characterized by inhibition of both pseudaffective responses. The effects of 5-HT receptor agonists and antagonists on resting blood pressure were also examined. The i.t. administration of 5-HT resulted in a dose-dependent elevation of the visceromotor threshold and inhibition of the pressor response to CRD. The 5-HT1A receptor agonist 8-OH-DPAT, the 5-HT1B receptor agonist RU-24969, the 5-HT2 receptor agonists DOI, MK-212 and alpha-methyl-5-HT and the 5-HT3 agonist 2-methyl-5-HT all dose-dependently inhibited the pressor response and dose-dependently elevated the visceromotor threshold to noxious CRD. The rank order of potency of these agonists was the same for both pseudaffective responses to CRD: DOI greater than or equal to 8-OH-DPAT greater than or equal to MK-212 = RU-24969 greater than or equal to alpha-methyl-5-HT = 2-methyl-5-HT much greater than 5-HT. The antinociceptive effects of 5-HT, RU-24969, alpha-methyl-5-HT and DOI were antagonized by i.t. pretreatment with methysergide. Intrathecal pretreatment with ketanserin antagonized the antinociceptive effects of MK-212 and MDL-72222 antagonized the effects produced by 2-methyl-5-HT in response to CRD. The antinociceptive effects produced by 8-OH-DPAT were not antagonized by i.t. pretreatment with methysergide. These results demonstrate that 5-HT1, 5-HT2 and 5-HT3 receptors in the spinal cord mediate antinociception in response to noxious CRD in conscious rats.
本研究检测了鞘内注射5-羟色胺（5-羟色胺，5-HT）及其他5-HT受体激动剂在以结肠扩张（CRD）作为有害内脏刺激的内脏痛模型中产生的抗伤害感受作用是否通过与脊髓5-HT1、5-HT2或5-HT3受体亚型相互作用介导。清醒大鼠的CRD可靠地引发两种假情感反射：强烈的升压反应和内脏运动反应。抗伤害感受以两种假情感反应均受抑制为特征。还检测了5-HT受体激动剂和拮抗剂对静息血压的影响。鞘内注射5-HT导致内脏运动阈值呈剂量依赖性升高，并抑制对CRD的升压反应。5-HT1A受体激动剂8-OH-DPAT、5-HT1B受体激动剂RU-24969、5-HT2受体激动剂DOI、MK-212和α-甲基-5-HT以及5-HT3激动剂2-甲基-5-HT均呈剂量依赖性抑制升压反应，并呈剂量依赖性提高对有害CRD的内脏运动阈值。这些激动剂对CRD两种假情感反应的效价排序相同：DOI≥8-OH-DPAT≥MK-212 = RU-24969≥α-甲基-5-HT = 2-甲基-5-HT＞＞5-HT。5-HT、RU-24969、α-甲基-5-HT和DOI的抗伤害感受作用被鞘内预先注射麦角新碱所拮抗。鞘内预先注射酮色林拮抗MK-212的抗伤害感受作用，MDL-72222拮抗2-甲基-5-HT对CRD产生的作用。8-OH-DPAT产生的抗伤害感受作用未被鞘内预先注射麦角新碱所拮抗。这些结果表明，脊髓中的5-HT1、5-HT2和5-HT3受体介导清醒大鼠对有害CRD的抗伤害感受作用。
Zotero 插件