About this trial
The feeling of pain is not just a sensory experience, but is also influenced by emotions, beliefs and expectations, making pain a highly subjective experience. This is evident in clinical practice, where the behavior of the physician and the treatment context can strongly influence the pain experience of patients. Research has shown that patients' expectation that a treatment will reduce pain influences individual perception of pain, even if the treatment has no active ingredient. The expectancy-induced analgesia emerges due to a modulation of the individual pain experience of patients by an engagement of endogenous inhibitory systems in the central nervous system.
The development of expectancy-induced analgesia can be generated in several ways. The investigators have previously demonstrated that social information and observational learning (e.g. the patient observes analgesia in another person receiving a treatment) can lead to expectancy-induced analgesia and pain reduction. However, the neural mechanisms (mechanisms in the brain) of how these expectancies are acquired and the neural mechanisms of analgesia induced by observational learning are unknown.
The investigators recently established a procedure to investigate neural mechanisms of observational learning in placebo analgesia. Here the investigators propose to investigate the influence of vasopressin, a neurotransmitter that is important for social interaction, on observational learning.
The investigators will use functional magnetic resonance imaging (fMRI), a non-invasive method, to investigate neural activity in humans. Participants will either receive vasopressin or saline with a nasal spray. During fMRI scanning, participants will then undergo an observational learning phase, where the study participants will learn the experience of analgesia in another person through a video, and a testing phase, where participants will perceive painful stimulations with the same cues as the observational phase. The comparison of the vasopressin group and the saline group will allow us to investigate how vasopressin influences behavioral effects of observational learning on pain perception as well as its effect on the neural processing of observational learning.
A better understanding of how the human brain processes observationally-induced analgesia would allow us to improve the therapeutic context of pain treatments by increasing the contextual factors which help patients cope with pain.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age ( 18-55 years old)
English speaker (written and spoken)
Disqualifiers
Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, degenerative neuromuscular disease, history of cancer within past 3 years
Any history of chronic pain disorder or currently in pain
Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 3 years.
Family (first degree) history of mania, schizophrenia, or other psychoses
Trial design
Parallel
Treatments tested in this trial
Arginine vasopressin
DrugIntranasal vasopressin will be administered shortly before the fMRI experiment.
Saline
Other interventionIntranasal saline will serve as a placebo for participants in the Saline Arm
Observational learning
BehavioralDuring the observational learning intervention, participants will learn the experience of analgesia in another person via a video. Participants will learn the analgesia nature of the placebo cream and the neutral nature of the control cream.
fMRI data aquisition
Other interventionAll participants from the intranasal vasopressin and intranasal saline groups will go through a fMRI data acquisition to obtain the brain structural, brain resting-states and functional MRI scans.
Treatment groups
Trial outcomes
Primary outcomes
Change in BOLD Singal in Supplementary Motor Area Compared to Whole Brain Average During the Painful Stimulation
Blood oxygenation level dependent (BOLD) responses will allow the identification of relative activation/deactivation in the brain as a result of events (e.g. painful stimulations) that will be given during the experiment. Changes in the Percentage of BOLD signal are calculated as the BOLD signal in the right supplementary motor area during the 20-second heat pain divided by the whole-brain average BOLD signal during that 20-second heat pain.
Secondary outcomes
Heating Temperature
On Day 1, the heating temperature was calibrated to the individual level. The heating temperature corresponding to 50 out of 100 visual analog scale pain ratings was selected as the testing temperature for day 2 (test).
Pain Ratings
Participants will provide their pain on a Visual Analogue Scale raging from 0=no pain to 100= maximum unbearable pain. Normal value will be absence of pain.
Other outcomes
Implicit Association Test (IAT) Response Latency Difference
The IAT is a behavioral test that examines racial biases via measuring the strength of associations between concepts (e.g., African-American, Asian, White) and evaluations (good, bad). Participants were asked to press a response key when they saw images (people) or words (good/bad) on the screen. Response latencies (RL) were measured in milliseconds using E-prime as the reaction time to press the response key. An RL difference (D) score was calculated as 1) Compute the standard deviation (SD) of RL from overall trials; 2) M1 is the mean of RL in the condition where "White" and "good" share the same response key. M2 is the mean of RL in the condition where "African-American/Asian people" and "good" share the same response key; 3) D = (M2-M1)/SD. The D score ranges from -2 to +2. Positive values indicate a racial preference for White people. Negative values indicate a racial preference for African-American/Black or Asian people. A value close to 0 indicates no racial preference.
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