Nocebo effects, negative responses to inert or active treatments which are putatively induced
by negative outcome expectations, have been shown to play a significant role in pain
perception. The underlying neurobiological mechanisms of these effects remain largely
unexplored. The primary objective of this study is to test the role of N-methyl-D-aspartate
(NMDA) receptor-dependent learning in an experimental model of conditioned nocebo effects on
self-reported pain. Secondary objectives are to examine the role of the NMDA manipulation and
related neural correlates during the acquisition and extinction of nocebo effects using
statistical learning models. This study will utilize a placebo controlled, double-blind
design with respect to the pharmacological administration of 80 mg D-Cycloserine (DCS), an
NMDA agonist, or placebo. Validated conditioning and verbal suggestion (VS) paradigms will
induce nocebo effects on pain in a random sample of 50 healthy adults. The primary endpoint
of the study is the magnitude of the induced nocebo effect on pain measured as the difference
between self-reported pain, between the first conditioned and control extinction trials.
Secondary endpoints include the classification analysis of the Blood Oxygen Level Dependent
(BOLD) responses of participants into pharmacological groups with multivariate pattern
analysis. This study will be conducted at Leiden University and the Leiden University Medical
Center (LUMC), The Netherlands.