Effects of Intranasal Oxytocin Administration on Social Influence Effects on Pain

Pain Clinical Trial

Official title:

Effects of Oxytocin Administration on Social Influence Effects on Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03060031
• Other study ID #: GRANT11076934
• Status: Completed
• Phase: Phase 1
• Start date: June 21, 2017
• Est. completion date: April 1, 2019

Study information

• Verified date: June 2019
• Source: University of Colorado, Boulder
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: April 1, 2019
• Est. primary completion date: March 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Oxytocin
Oxytocin intranasal administration, 40 IU, 5 puffs per nostril at 4 IU per puff delivered approximately 45 minutes prior to pain tasks.
• Placebo
Placebo intranasal administration, 5 puffs per nostril delivered approximately 45 minutes prior to pain tasks

Locations

Country	Name	City	State
United States	Clinical Translational Research Center	Boulder	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Boulder

Country where clinical trial is conducted

United States, 

References & Publications (35)

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pain expectation rating score made on a Visual Analog Scale (VAS) after administration of Oxytocin vs. Placebo	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)).	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.
Primary	Change in pain rating score made on a Visual Analog Scale (VAS) after administration of Oxytocin vs. Placebo	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)).	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.
Primary	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	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)).	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.