The role of serotonin in visceral and somatic placebo analgesia

尚未直接比较健康受试者对实验引起的内脏和躯体疼痛的敏感性，也没有进行内脏和躯体安慰剂止痛的比较。在总共3个实验和1个特殊实验室分析中，我们将阐明两者之间的联系。我们将进一步研究中枢和/或外周作用的5-羟色胺是否以及在多大程度上参与内脏和躯体的安慰剂止痛。实验1直接比较受试者内脏和躯体疼痛敏感度的变异性，并为随后的测试建立“正常”值；它还将建立内脏和躯体系统的安慰剂止痛程序，并将在受试者内部和跨受试者之间进行比较。实验2将使用色氨酸戒断(急性色氨酸耗竭，ATD)导致中枢和外周5-羟色胺水平普遍下降，实验3将使用选择性5-羟色胺再摄取抑制剂(SSRI)增强中枢和外周5-羟色胺系统，以操纵内脏和躯体安慰剂镇痛。所有接受安慰剂镇痛的受试者的血液样本将被用来测试5-羟色胺系统的两种多态(5-羟色胺转运体连接多态区域(5HTTLRP)和TPH2多态)是否与更高的安慰剂反应率以及对内脏和躯体安慰剂镇痛中各种5-羟色胺能挑战的反应有关。

A direct comparison of sensitivity towards experimentally induced visceral and somatic pain in healthy subjects has not yet been performed, and neither has the comparison of visceral and somatic placebo analgesia. In altogether 3 Experiments and 1 post-hoc laboratory analysis we will elucidate the association between both. We will further investigate whether and to what degree centrally and/or peripherally acting serotonin is involved in visceral and somatic placebo analgesia. Experiment 1 directly compares within-subjects variability of visceral and somatic pain sensitivity and establishes the „norm“ values for the subsequent tests; it will also establish a placebo analgesia procedure for the visceral and somatic system and will compare both within and across subjects. Experiment 2 will use a general depletion of central and peripheral serotonin levels by tryptophan withdrawal (acute tryptophan depletion, ATD), Experiment 3 will enhance the central and peripheral serotonin system using a selective serotonin reuptake inhibitor (SSRI) to manipulate visceral and somatic placebo analgesia. The blood samples of all subjects exposed to placebo analgesia will be used to test whether two polymorphisms of the serotonin system (the serotonin transporter-linked polymorphic region (5HTTLRP) and the TPH2 polymorphism) are associated with higher placebo response rates and with response to the various serotonergic challenges in visceral and somatic placebo analgesia.