Nitrous Oxide Neuroimaging

Official title

Functional MRI of Nitrous Oxide Inhalation in Volunteer Subjects

Overview

The purpose of this study is to determine the effects of acute pain on long-term memory and conditioned physiologic responses in the presence and absence of low dose nitrous oxide. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will occur over 2 visits and involves no long-term follow up.

Detailed description

This is a non-randomized, clinical trial study of healthy volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of inhalational nitrous oxide on pain processing and cognitive function. Sedative doses of nitrous oxide will be targeted, and steady-state end-tidal (expired) concentrations achieved, while subjects perform a pain and memory cognitive task. At both no-drug baseline and the targeted doses, task and resting-state functional magnetic resonance imaging (MRI) scans will be acquired, and this data will be analyzed subsequently for task-related brain activity (from pain processing and memory formation) and functional connectivity. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of inhalational nitrous oxide in the context of painful stimulation.

The investigators propose to complete the following 3 Aims, at a targeted sedative dose of nitrous oxide, compared to no-drug baseline, using functional MRI:

Aim 1: Determine how the brain response to acute pain stimulation is modulated by nitrous oxide. It is anticipated that nitrous oxide will correlate to decreased activation in both somatosensory (thalamus, insula, primary somatosensory/motor) and affective (anterior cingulate) components of the pain processing brain areas.

Aim 2: Determine how memory encoding is modulated by nitrous oxide, in the context of periodic painful stimulation. It is anticipated that nitrous oxide will correlate to decreased activation in both the explicit memory (hippocampus, parahippocampus) and associative learning (amygdala, anterior cingulate) brain systems.

Aim 3: Determine the neural effects of inhalational nitrous oxide on brain connectivity both at rest and during the combined pain and memory task performance. It is anticipated that nitrous oxide will cause widespread dose-dependent decreases in long-range functional connectivity between brain areas known to be involved in pain processing and to the default mode network, and that this connectivity will differ between the resting (task-free) and periodic pain states.

Interventions

• Drug Nitrous oxide
  After a no-drug control period, subjects will inhale nitrous oxide, administered via a breathing circuit and face mask, until a steady-state target end-tidal expired concentration is reached. During the drug condition, subjects will receive low-dose nitrous oxide (% corresponding to Minimum Alveolar Concentration).
• Device Peripheral Nerve Stimulation
  Experimental acute pain stimulus will be delivered using a nerve stimulator. These painful shocks will be paired with a fixed number of the experimental cues, in a pattern that appears random to participants.

Primary outcome measures

• Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide condition [Time frame: Visit 1: Immediate; average activity, calculated from each task scan]
• Resting-state functional connectivity difference: Drug-free minus nitrous oxide condition [Time frame: Visit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.]

Secondary outcome measures (1)

• Explicit memory performance [Time frame: Visit 2: 24 hours post-learning experiment]

Eligibility criteria

Inclusion criteria

• have none of the specific exclusion criteria
• have a valid email address and valid phone number throughout the study
• free from any non-MRI compatible implants

Exclusion criteria

• are pregnant or attempting to conceive
• body mass index (BMI) > 35
• significant memory impairment or hearing loss
• sleep apnea
• chronic pain or frequently taking pain medication (including tramadol)
• any severe or poorly-controlled medical problem (hypertension, diabetes)
• neurologic or psychiatric disease, including anxiety, and depression
• severe cardiac disease
• history of methylenetetrahydrofolate reductase (MTHFR) deficiency or variant mutation, as assessed by personal report
• recent ear or eye surgery
• being claustrophobic
• have metal implants or non-removable metal piercings
• having a history of adverse reaction to anesthetics
• daily alcohol or heavy alcohol use; history of alcohol abuse
• current daily smoker
• regular or recent marijuana use (including prescribed/medical marijuana)
• illicit drug use, i.e., street drugs
• regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Pittsburgh — Pittsburgh

Identifiers

NCT: NCT06702631 · STUDY24100059 · R35GM146822

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗