Rueff A, Dray A
Sandoz Institute for Medical Research, London, U.K.
Neuroscience. 1992 Oct;50(4):899-905. doi: 10.1016/0306-4522(92)90213-l.
The effects of 5-hydroxytryptamine on peripheral nociceptive fibres were studied in an in vitro preparation of the neonatal rat spinal cord with attached tail. The activation of peripheral fibres in the tail by noxious stimuli (bradykinin, capsaicin, heat) was recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by brief applications of submaximal or threshold concentrations of bradykinin or capsaicin to the tail were enhanced by 5-hydroxytryptamine and the 5-hydroxytryptamine1C/5-hydroxytryptamine2-receptor agonist alpha-methyl-5-hydroxtryptamine but not by the 5-hydroxytryptamine3-receptor agonist 2-methyl-5-hydroxytryptamine or the 5-hydroxytryptamine1-receptor agonist 5-carboxamidotryptamine. Sensitization induced by 5-hydroxytryptamine and alpha-methyl-5-hydroxytryptamine was blocked by the selective 5-hydroxytryptamine2-receptor antagonist ketanserin. Neither the 5-hydroxytryptamine3/5-hydroxytryptamine4-receptor antagonist ICS 205-930 nor the 5-hydroxytryptamine1/5-hydroxytryptamine2-receptor antagonist methiothepin blocked the 5-hydroxytryptamine-induced sensitization. The responses evoked by submaximal thermal stimuli were also enhanced following the sensitization of peripheral nociceptors with 5-hydroxytryptamine or alpha-methyl-5-hydroxytryptamine. The alpha-methyl-5-hydroxytryptamine-induced enhancement of thermal responses was reduced by ketanserin. 5-Hydroxytryptamine did not evoke a ventral root response unless peripheral fibres were sensitized with threshold concentrations of bradykinin or capsaicin. This effect was mimicked under the same conditions by 5-carboxamidotryptamine but not by alpha-methyl-5-hydroxytryptamine or 2-methyl-5-hydroxytryptamine. The excitatory effect of 5-hydroxytryptamine was blocked by methiothepin but not by ICS 205-930 or ketanserin. Neither 5-hydroxytryptamine-induced sensitization nor 5-hydroxytryptamine-evoked activation of peripheral fibres was blocked by indomethacin. These data indicate that two types of receptor are involved in the peripheral actions of 5-hydroxytryptamine in nociception. 5-Hydroxytryptamine-induced sensitization involves a 5-hydroxytryptamine2-receptor, whereas 5-hydroxytryptamine-evoked excitation involves a 5-hydroxytryptamine1-like-receptor.
采用新生大鼠脊髓-尾标本的体外制备方法，研究了5-羟色胺对外周伤害性纤维的作用。通过记录脊髓腰段（L3-L5）腹根的去极化，来检测伤害性刺激（缓激肽、辣椒素、热刺激）对尾部外周纤维的激活作用。对尾部施加亚最大或阈浓度的缓激肽或辣椒素所诱发的反应，可被5-羟色胺及5-羟色胺1C/5-羟色胺2受体激动剂α-甲基-5-羟色胺增强，但5-羟色胺3受体激动剂2-甲基-5-羟色胺或5-羟色胺1受体激动剂5-羧基酰胺色胺则无此作用。5-羟色胺及α-甲基-5-羟色胺所诱导的致敏作用，可被选择性5-羟色胺2受体拮抗剂酮色林阻断。5-羟色胺3/5-羟色胺4受体拮抗剂ICS 205-930及5-羟色胺1/5-羟色胺2受体拮抗剂甲硫噻吩均不能阻断5-羟色胺诱导的致敏作用。在用5-羟色胺或α-甲基-5-羟色胺使外周伤害性感受器致敏后，亚最大热刺激所诱发的反应也增强。酮色林可减弱α-甲基-5-羟色胺所诱导的热反应增强作用。除非外周纤维先用阈浓度的缓激肽或辣椒素致敏，否则5-羟色胺不会诱发腹根反应。在相同条件下，5-羧基酰胺色胺可模拟此效应，但α-甲基-5-羟色胺或2-甲基-5-羟色胺则无此作用。5-羟色胺的兴奋作用可被甲硫噻吩阻断，但ICS 205-930或酮色林则无此作用。消炎痛不能阻断5-羟色胺诱导的致敏作用及5-羟色胺诱发的外周纤维激活作用。这些数据表明，5-羟色胺在外周伤害感受中的作用涉及两种类型的受体。5-羟色胺诱导的致敏作用涉及5-羟色胺2受体，而5-羟色胺诱发的兴奋作用涉及5-羟色胺1样受体。
