Memory Modulation by Pain During Anesthesia (MMA)

University of Pittsburgh

Status and phase: Completed; Phase 1

Conditions: Amnesia; Pain; Anesthesia

Treatments: Drug: Ketamine; Drug: Dexmedetomidine; Device: Peripheral nerve stimulation; Drug: Midazolam

Study type: Interventional

Funder types: Other

Identifiers

NCT02515890

PRO14050609

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 39 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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32 participants in 5 patient groups

Dexmedetomidine Only

Experimental group

Description:

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

Treatment:

Device: Peripheral nerve stimulation

Drug: Dexmedetomidine

Midazolam Only

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Device: Peripheral nerve stimulation

Ketamine Only

Experimental group

Description:

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

Treatment:

Device: Peripheral nerve stimulation

Drug: Ketamine

Saline/Midazolam/Saline/Ketamine

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Device: Peripheral nerve stimulation

Drug: Ketamine

Saline/Ketamine/Saline/Midazolam

Experimental group

Description:

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.

Treatment:

Drug: Midazolam

Device: Peripheral nerve stimulation

Drug: Ketamine