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Effects of Intranasal Oxytocin Administration on Social Influence Effects on Pain

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ClinicalTrials.gov Identifier: NCT03060031
Recruitment Status : Completed
First Posted : February 23, 2017
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Tor Wager, University of Colorado, Boulder

Brief Summary:
This experiment will explore the joint effects of social information, social support, associative learning, and oxytocin on the development of placebo analgesia. The investigators predict that socially transmitted placebo effects will be enhanced by nasal administration of oxytocin, whereas associative learning effects on pain will not be altered by this pharmacological manipulation

Condition or disease Intervention/treatment Phase
Pain Drug: Oxytocin Drug: Placebo Phase 1

Detailed Description:

Background:

The placebo literature suggests that both conceptual (i.e. socially instructed beliefs) and associative learning processes are critical for the genesis of placebo effects. Several studies have performed placebo 'conditioning' (associating a sham treatment with reduced pain through repeated experience) but interfered with conceptual processing by informing subjects that the intensity of the stimulus was being lowered. This manipulation prevented the attribution of pain reductions to the placebo treatment during the learning process. These studies showed no conditioned analgesia. However, when the same 'conditioning' was performed without the verbal explanation for why the treatment seemed to work, robust placebo effects were created. Conceptual processes appear to be critical. Conversely, several studies have manipulated conceptual expectations alone, by manipulating verbal instructions, and have found markedly reduced or absent placebo analgesia on both pain report and brain event-related potentials. Learning by experience also seems to be critical.

These studies separately have led to the conclusions that 'expectancy' and 'conditioning' are each critical processes, and debates have focused on which one is the driver of placebo effects. The investigators propose another view: Both processes are critical, and they interact. Experience drives changes in value learning systems, but in any type of value learning, there is a 'credit assignment' problem, and the brain must decide which cue-outcome associations to update as a result of experience: Is the pain reduced because the treatment was effective or because the cause of pain changed? Conceptual processes fill the gap, drawing on explicit memory and generalization from similar past experiences to solve the credit assignment problem, creating analgesia if experienced relief is attributed to the treatment. This view is compatible with older information based theories of conditioning and new evidence that rats and humans alike maintain expectancies about specific outcomes and mental models of contingencies that are distinct from associative learning. In spite of dozens of published studies demonstrating effective placebo analgesia with the established paradigm the investigators use, the precise nature of the learning that occurs is unknown, because placebo analgesia has not typically been studied from a learning-systems perspective. The aim of the present study is to assess the influence of social information and associative learning on placebo analgesia.

In addition, interactions between neurochemical systems and placebo analgesia have hardly been explored, and this proposal represents a significant effort in that regard. For example, oxytocin interacts synergistically with opioids in the PAG (periaqueductal gray) (and CCK (Cholecystokinin)) to relieve pain, and in a separate literature reliably increases trust and reduces anxiety in interpersonal situations. In spite of the fact that oxytocin has been proposed as central to the placebo effect and can be administered to humans with no known subjective effects or side effects, its role in placebo analgesia has not been explored extensively. The experiment proposed here will clarify the roles of the oxytocin system and its contributions to social facilitation of analgesia, and will be instrumental in developing a systems-based model of placebo effects.

Experimental Design:

Participants will perform two tasks in each experimental session. First, they will perform a social-influence and learning task to investigate the effects of oxytocin on social instruction effects and learning on pain. Second, they will perform a social-support during pain, to test the effects of oxytocin on the pain-alleviating effects of social support during pain.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Oxytocin Administration on Social Influence Effects on Pain
Actual Study Start Date : June 21, 2017
Actual Primary Completion Date : March 5, 2019
Actual Study Completion Date : April 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
Experimental: Oxytocin
Each participant will undergo pain tasks after self-administration of oxytocin
Drug: Oxytocin
Oxytocin intranasal administration, 40 IU, 5 puffs per nostril at 4 IU per puff delivered approximately 45 minutes prior to pain tasks.
Other Name: Syntocinon

Placebo Comparator: Placebo
Each participant will undergo pain tasks after self-administration of placebo
Drug: Placebo
Placebo intranasal administration, 5 puffs per nostril delivered approximately 45 minutes prior to pain tasks




Primary Outcome Measures :
  1. Change in pain expectation rating score made on a Visual Analog Scale (VAS) after administration of Oxytocin vs. Placebo [ Time Frame: Measured during pain tasks at session 1 (within one month of screening survey completion) and 2 which will be within one week of each other. ]
    Self reported expectation of pain intensity using the VAS ranging from 0-100 (with 0 representing "no pain at all" and 100 representing "most intense pain imaginable (in the context of the experiment)).

  2. Change in pain rating score made on a Visual Analog Scale (VAS) after administration of Oxytocin vs. Placebo [ Time Frame: Measured during pain tasks at session 1(within one month of screening survey completion) and 2 which will be within one week of each other. ]
    Self reported pain intensity using the VAS ranging from 0-100 (with 0 representing "no pain at all" and 100 representing "most intense pain imaginable (in the context of the experiment)).

  3. Change in pain unpleasantness rating score during hand holding and control conditions made on a Visual Analog Scale (VAS) after administration of Oxytocin vs. Placebo [ Time Frame: Measured during pain tasks at session 1 (within one month of screening survey completion)and 2 which will be within one week of each other. ]
    Self reported pain unpleasantness using the VAS ranging from 0-100 (with 0 representing "no pain at all" and 100 representing "most intense pain imaginable (in the context of the experiment)).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject is a volunteer between 18 and 40 years of age.
  • If female, subject is non-lactating, not pregnant, and using a reliable contraception method
  • Subject is able to read and speak English.
  • Subject is able and willing to provide written informed consent.
  • Subject is able to understand and follow the instructions of the investigator and understand all screening questionnaires.
  • Subject is in good health.
  • For participants to be eligible for all tasks of the study, the participant must have a romantic partner and be willing to bring the partner to the study session.

Exclusion Criteria:

  • Tests positive on the 14 panel poly-substance urine drug screen for illicit substances (e.g., marijuana (THC), cocaine (COC), phencyclidine (PCP), amphetamine (AMP), ecstasy (MDMA), methamphetamine (Mamp), opiates (OPI), oxycodone (OXY), methadone (MTD), barbiturates (BAR), benzodiazepines (BZO), buprenorphine (BUP), tricyclic antidepressants (TCA), propoxyphene (PPX))
  • Chronic Pain
  • Do not have the ability to tolerate heat pain applied to the forearm
  • Have temporary abnormal levels of pain
  • Have score of > 19 using the Center for Disease and Epidemiology Depression Scale
  • Current treatment (e.g., medications or therapy) for psychiatric disorders, including mood, anxiety, substance abuse, Attention-deficit/hyperactivity disorder (ADHD), psychosis; Neurological disorders (e.g., taking dopamine agonists for Parkinson's); Cardiovascular disease or medication (e.g., taking ACE (angiotensin-converting-enzyme) inhibitors for cardiac remodeling)
  • Frequent smoking (> 5 cigarettes / day); frequent alcohol use (>14 drinks / week); frequent migraines (> 5 / month on average) or a history of neurologic disease or neuropathic pain.
  • Any allergy to Oxytocin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03060031


Locations
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United States, Colorado
Clinical Translational Research Center
Boulder, Colorado, United States, 80309
Sponsors and Collaborators
University of Colorado, Boulder
Investigators
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Principal Investigator: Tor D Wager, Ph. D. University of Colorado, Boulder

Publications:

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Responsible Party: Tor Wager, Director, Cognitive and Affective Neuroscience Laboratory; Professor, Department of Psychology and Neuroscience and the Institute for Cognitive Science, University of Colorado, Boulder
ClinicalTrials.gov Identifier: NCT03060031     History of Changes
Other Study ID Numbers: GRANT11076934
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tor Wager, University of Colorado, Boulder:
Oxytocin

Additional relevant MeSH terms:
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Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs