Pain, Learning, and Nocebo

• Status: Not yet recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Leiden University Medical Center
• Collaborator: Leiden University
• Treatments: Cycloserine

Criteria

Inclusion Criteria:

• Aged 18 - 35 years

• Good understanding of the English language

• Normal or corrected to normal vision

Exclusion Criteria:

A potential participant who meets any of the following exclusion criteria will be excluded from participation in this study:

1. History of serious or chronic medical or psychiatric conditions (e.g., convulsions (epilepsy), cardiovascular problems, depression; careful and detailed screening will be carried out for both medical and psychiatric conditions)

2. History of chronic pain or itch conditions

3. Experiencing pain or itch of 1 or more on a 0-10 pain / itch NRS on the day of testing

4. Currently using antihistamines, analgesic medication, or itch-reducing medication (in the 24 hours prior to testing)

5. Use of psychotropic drugs (including recreational drugs such as cannabis and psychotropic prescription-medication; in the past month)

6. Currently being (or intending to become) pregnant, or currently breastfeeding, or planning to father a child in the next 3 months

7. Colour-blindness

8. Body Mass Index under 16 or over 30

9. Meeting any exclusion criteria in the fMRI examination questionnaire which would prohibit fMRI scanning.

10. Having too high of a threshold for pain (where high pain cannot be induced with temperatures lower than 49.5 °C).