222 differently in different doses. In lower doses (in most studies varying between 50-250 mg) it acts as a partial agonist at the glycine modulatory site of NMDA receptors 29. To our knowledge, no studies have examined the role of NMDA-mediated learning in nocebo effects. Recent findings on extinction-learning and exposure therapy indicates that DCS may be a promising agent for augmenting NMDA-dependent learning 27,30,31. DCS has also been shown to enhance performance on declarative learning 32 and generalization of conditioned effects to novel contexts 33. This evidence suggests that by agonizing NMDA receptors, DCS enhances specific learning processes, and can be used to manipulate and investigate the specific learning mechanisms involved in nocebo effects. By utilizing fMRI while pharmacologically agonizing NMDA-mediated learning during nocebo induction, precise neural processes involved in learned pain can be examined. In the present study we aim to investigate for the first time the role of NMDA-receptor dependent learning in the acquisition and extinction of nocebo effects. As compared to placebo administration, we hypothesize that DCS will augment the acquisition of nocebo hyperalgesia and will induce nocebo effects that are more resistant to extinction. We further hypothesize that differential brain activation will be detected between the DCS and placebo groups during nocebo acquisition, evocation, and extinction, in a number of a priori regions of interest such as the prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus, that were implicated in previous nocebo studies 34. We also hypothesize that neural activation will differ between the experience of nocebo-augmented pain and the experience of pain stimulations of the same high intensity.
RkJQdWJsaXNoZXIy MTk4NDMw