Effects of Intranasal Oxytocin Administration on Social Influence Effects on Pain
Condition: Pain
Study type: Interventional
Phase: Phase 1

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
    

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.
    

Intervention name(s): Oxytocin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oxytocin intranasal administration, 40 IU, 5 puffs per nostril at 4 IU per puff delivered approximately 45 minutes prior to pain tasks.; Placebo intranasal administration, 5 puffs per nostril delivered approximately 45 minutes prior to pain tasks
Other intervention name(s): Syntocinon
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Oxytocin