The role of serotonin in visceral and somatic placebo analgesia

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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.