Print Email Facebook Twitter A randomized pharmacological fMRI trial investigating d-cycloserine and brain plasticity mechanisms in learned pain responses Title A randomized pharmacological fMRI trial investigating d-cycloserine and brain plasticity mechanisms in learned pain responses Author Thomaidou, Mia A. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) Blythe, Joseph S. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) Veldhuijzen, Dieuwke S. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) Peerdeman, Kaya J. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) van Lennep, Johan (Hans) P.A. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) Giltay, Erik J. (Universiteit Leiden; Leiden Institute for Brain & Cognition, Leiden) Cremers, Henk R. (Universiteit van Amsterdam) Evers, A.W.M. (TU Delft Applied Ergonomics and Design; Universiteit Leiden; Leiden University Medical Center) Date 2022 Abstract Learning and negative outcome expectations can increase pain sensitivity, a phenomenon known as nocebo hyperalgesia. Here, we examined how a targeted pharmacological manipulation of learning would impact nocebo responses and their brain correlates. Participants received either a placebo (n = 27) or a single 80 mg dose of d-cycloserine (a partial NMDA receptor agonist; n = 23) and underwent fMRI. Behavioral conditioning and negative suggestions were used to induce nocebo responses. Participants underwent pre-conditioning outside the scanner. During scanning, we first delivered baseline pain stimulations, followed by nocebo acquisition and extinction phases. During acquisition, high intensity thermal pain was paired with supposed activation of sham electrical stimuli (nocebo trials), whereas moderate pain was administered with inactive electrical stimulation (control trials). Nocebo hyperalgesia was induced in both groups (p < 0.001). Nocebo magnitudes and brain activations did not show significant differences between d-cycloserine and placebo. In acquisition and extinction, there were significantly increased activations bilaterally in the amygdala, ACC, and insula, during nocebo compared to control trials. Nocebo acquisition trials also showed increased vlPFC activation. Increased opercular activation differentiated nocebo-augmented pain aggravation from baseline pain. These results support the involvement of integrative cognitive-emotional processes in nocebo hyperalgesia. To reference this document use: http://resolver.tudelft.nl/uuid:2b02d1b9-5e87-4d25-b3b7-9fc46691b2db DOI https://doi.org/10.1038/s41598-022-23769-7 ISSN 2045-2322 Source Scientific Reports, 12 (1) Part of collection Institutional Repository Document type journal article Rights © 2022 Mia A. Thomaidou, Joseph S. Blythe, Dieuwke S. Veldhuijzen, Kaya J. Peerdeman, Johan (Hans) P.A. van Lennep, Erik J. Giltay, Henk R. Cremers, A.W.M. Evers Files PDF s41598_022_23769_7_1.pdf 2.33 MB Close viewer /islandora/object/uuid:2b02d1b9-5e87-4d25-b3b7-9fc46691b2db/datastream/OBJ/view