Memory Modulation by Pain During Anesthesia (MMA)

June 22, 2020 updated by: Keith M. Vogt, MD, PhD, University of Pittsburgh

Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics

The purpose of this study is to determine the effects of pain on facilitating long-term auditory memory in the presence and absence of distinct intravenous anesthetics. The ability to identify previously presented words from a list assessed the degree of memory formation. In a subset of subjects, functional magnetic resonance imaging was used to identify the neural correlates of memory inhibition or facilitation by the combination of pain and anesthetic used.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study adds specific details to the current incomplete body of knowledge examining the effect of pain on memory formation under the influence of anesthetic agents.

Pain and anesthetic agents were administered as experimental variables in this study. Healthy adult subjects were played repeated lists of words and performed several decision-making tasks that encourage memory encoding. Some words were consistently paired with painful electric shock, and was anticipated to improve subsequent memory performance specifically for those items. The same experiment was repeated in all subjects during the administration of 1-2 possible agents that reduce memory formation: dexmedetomidine, a predominantly sedative agent, and midazolam, a well-known amnestic agent, and ketamine, a well-known dissociative analgo-sedative. The extent to which pain modulates memory performance under the effects of the anesthetic agents was the primary outcome of interest.

Further, a subset of the subjects performed the same experimental procedures while undergoing functional magnetic resonance imaging, which continuously reflects neuronal activity throughout the brain. Classic memory areas were predicted to be activated by the auditory processing task, but how these neural circuits change under the two anesthetic agents with the concomitant experience of pain were of interest. It was anticipated that pain recruits a parallel memory pathway using limbic structures, known for their involvement in fear conditioning. Additionally, stronger and more diffuse cortical processing likely occurs with concomitant pain, as level of sedation was reduced by this strong stimulus. Discovering the anatomic correlates specific to each experimental variable (pain and anesthetic), and their interplay, may help refine our model of brain function during the dynamics of pain and sedation.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 39 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy adult volunteers, with normal memory and hearing, whose native language is English

Exclusion Criteria:

  • pregnancy
  • significant memory or hearing loss
  • sleep apnea
  • chronic pain
  • metal or electronic implants
  • claustrophobia
  • Currently taking: antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, sleep-aids, or pain medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dexmedetomidine Only
All subjects receive saline (control), followed by a dexmedetomidine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Drug: Dexmedetomidine
Selected subjects received this drug during a portion of the study
Other Names:
  • Precedex
Device: Peripheral nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
Other Names:
  • electric nerve stimulation
EXPERIMENTAL: Midazolam Only
Subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Device: Peripheral nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
Other Names:
  • electric nerve stimulation
Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Names:
  • Versed
EXPERIMENTAL: Ketamine Only
All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.
Device: Peripheral nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
Other Names:
  • electric nerve stimulation
Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Names:
  • Ketalar
EXPERIMENTAL: Saline/Midazolam/Saline/Ketamine

All subjects receive saline (control), followed by midazolam infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by ketamine infusion.
Device: Peripheral nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
Other Names:
  • electric nerve stimulation
Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Names:
  • Versed
Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Names:
  • Ketalar
EXPERIMENTAL: Saline/Ketamine/Saline/Midazolam

All subjects receive saline (control), followed by ketamine infusion. They also experience intermittent experimental pain delivered by peripheral nerve stimulation.

Subjects then returned at least 1 week later for another set of experimental sessions with the same design, however the saline was followed by midazolam infusion.
Device: Peripheral nerve stimulation
Experimental acute pain stimulus was delivered using a nerve stimulator. These painful shocks were paired randomly with some of the auditory experimental cues.
Other Names:
  • electric nerve stimulation
Drug: Midazolam
Selected subjects received this drug during a portion of the study
Other Names:
  • Versed
Drug: Ketamine
Selected subjects received this drug during a portion of the study
Other Names:
  • Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Memory Testing
Time Frame: At memory testing 1 day later
Subjects completed the Remember, Know, New (RKN) task during next day testing. Their d' memory score was calculated based on their ability to discriminate between previously heard words and new words. A higher d' score indicates stronger recollection. D' scores were compared across the control condition (saline) and the drug conditions dexmedetomidine, midazolam, and ketamine. Performance was also calculated according to words associated with Pain and No Pain conditions.
At memory testing 1 day later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

Foundation for Anesthesia Education and Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 19, 2015

Primary Completion (ACTUAL)

December 12, 2018

Study Completion (ACTUAL)

December 12, 2018

Study Registration Dates

First Submitted

August 3, 2015

First Submitted That Met QC Criteria

August 4, 2015

First Posted (ESTIMATE)

August 5, 2015

Study Record Updates

Last Update Posted (ACTUAL)

July 1, 2020

Last Update Submitted That Met QC Criteria

June 22, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO14050609

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be published. After all analysis and dissemination is complete, functional images will be shared via data repository.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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