Nadeson R, Goodchild C S
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia.
Br J Anaesth. 2002 May;88(5):679-84. doi: 10.1093/bja/88.5.679.
Intrathecal administration of 5-hydroxytryptamine (5-HT) is antinociceptive to noxious heat and electrical stimuli. The contributions of different receptor subtypes to the antinociceptive effects of 5-HT are controversial. The main reasons for this are the poor receptor subtype selectivity of some agonist drugs and the difficulty of restricting drug action to the spinal cord in some experimental paradigms. This study investigated the roles of different 5-HT receptor subtypes involved in the spinal cord control of the nociception produced by these two nociceptive testing paradigms.
Tail-flick latency and electric current threshold for nociception were measured in an acute pain model that allowed the study of the antinociceptive effects of intrathecally administered drugs that were due to actions of these drugs at spinal cord receptors. Experiments were performed in male Wistar rats with chronically implanted lumbar subarachnoid catheters. Dose-response curves for spinally mediated antinociceptive effects of agonists selective for 5-HT receptor subtypes were constructed.
The 5-HT1 agonist 1-(3-chlorophenyl)-piperazine dihydrochloride caused a dose-dependent antinociceptive effect, measured by both nociceptive tests. However, 8-hydroxy-DPAT (selective 5-HT1A agonist) produced antinociception assessed by electric current but not tail flick. A 5-HT1A-selective antagonist, 4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)-piperazine, reversed the antinociception in the electrical test produced by both of these agonists but the tail-flick latency effects after intrathecal 1-(3-chlorophenyl)-piperazine were not suppressed by this antagonist.
We conclude that 5-HT1A receptors in the spinal cord are involved in the nociceptive mechanisms assessed by noxious electrical stimuli. Other 5-HT1 receptors (non 5-HT1A receptors) are involved in the spinally mediated antinociception assessed by thermal noxious stimuli.
鞘内注射5-羟色胺（5-HT）对热刺激和电刺激具有抗伤害感受作用。不同受体亚型对5-HT抗伤害感受作用的贡献存在争议。主要原因是一些激动剂药物对受体亚型的选择性较差，以及在某些实验范式中难以将药物作用限制在脊髓。本研究调查了不同5-HT受体亚型在脊髓控制这两种伤害性测试范式所产生的伤害感受中的作用。
在急性疼痛模型中测量甩尾潜伏期和伤害性电流阈值，该模型允许研究鞘内给药药物因其在脊髓受体上的作用而产生的抗伤害感受作用。实验在长期植入腰段蛛网膜下腔导管的雄性Wistar大鼠中进行。构建了对5-HT受体亚型具有选择性的激动剂的脊髓介导抗伤害感受作用的剂量反应曲线。
5-HT1激动剂1-(3-氯苯基)-哌嗪二盐酸盐通过两种伤害性测试均产生剂量依赖性抗伤害感受作用。然而，8-羟基-DPAT（选择性5-HT1A激动剂）通过电流评估产生抗伤害感受作用，但甩尾试验未显示该作用。5-HT1A选择性拮抗剂4-[3-(苯并三唑-1-基)丙基]-1-(2-甲氧基苯基)-哌嗪可逆转这两种激动剂在电测试中产生的抗伤害感受作用，但鞘内注射1-(3-氯苯基)-哌嗪后对甩尾潜伏期的影响未被该拮抗剂抑制。
我们得出结论，脊髓中的5-HT1A受体参与了通过有害电刺激评估的伤害感受机制。其他5-HT1受体（非5-HT1A受体）参与了通过热有害刺激评估的脊髓介导的抗伤害感受作用。
