Anesthesia, Pain
Conditions
Keywords
lidocaine, functional MRI, electric nerve stimulation, functional connectivity
Brief summary
The purpose of this study is to characterize the effects of intravenous lidocaine on pain processing and cognitive function. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will consist of 1 visit and involves no long-term follow up.
Detailed description
This is an observational cohort study of volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of intravenous lidocaine on pain processing and cognitive function. A steady-state effect-site concentration of lidocaine will be achieved, and a short battery of cognitive behavioral tasks will be employed. At the dose target, pain task functional MRI and resting-state connectivity will be determined. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of intravenous lidocaine, a commonly-used opioid alternative analgesic agent. Aim1: Determine cognitive behavioral effects of a steady-state dose of IV lidocaine using a short battery of tasks. The investigators hypothesize that the administration of lidocaine will correlate to decreased pain ratings, slowed psychomotor response, and decreased memory encoding. Aim2: Determine the neural effects of a steady-state dose of IV lidocaine in response to acute pain, and on resting connectivity. The investigators hypothesize that pain task-related activation will decrease in the insula and anterior cingulate, corresponding to decreased ratings of pain intensity and unpleasantness. Additionally, the investigators expect widespread decreases in long-range functional connectivity between brain areas know to be involved in these two areas and other known to be involved in pain processing.
Interventions
DEVICEPeripheral Nerve Stimulation
Experimental acute pain stimulus will be delivered using an electric nerve stimulator.
DRUGLidocaine IV
Subjects will receive an intravenous infusion of lidocaine for about 30 minutes.
Sponsors
National Institute of General Medical Sciences (NIGMS)
Keith M Vogt
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults aged 18 to 70 * Be of normal body-weight * Be generally healthy * Have none of the specific
Exclusion criteria
* Have a valid email address and phone number throughout the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition | 4.5 minutes | The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Primary outcome is listed for the Right insula, but similar scores are calculated throughout the brain. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate stronger correlation between functional MRI signal change and the task timing, with positive values indicating increases in fMRI signal and negative Z-scores indicating decreases. Practically, higher positive Z-scores indicate increased brain activity and larger negative Z-scores indicate decreased brain activity. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score. |
| Resting-state Functional Connectivity Difference: Drug-free Minus Lidocaine | 8 minutes | Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between drug-free and lidocaine conditions. The reported value is the FC change between the right insula and anterior cingulate. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the drug-free condition, and more negative scores mean stronger connectivity with lidocaine. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Score Difference, Drug-free Condition Minus Lidocaine Condition | 12 minutes | Numerical rating scale (0-10) pain score difference, comparing drug-free to the steady-state dose of lidocaine. Higher pain scores indicate more pain; a positive difference between pain score during the drug-free condition minus the value during the lidocaine condition indicates pain reduction (a better outcome). |
| Memory Performance Difference, Drug-free Minus Lidocaine Condition | 3 minutes | Performance on a short computer-based test of memory for visual pictures will be quantified using signal detection metric d-prime, reflecting ability (in standard deviation units) to detect previously-seen images from the background noise of previously un-seen images. Differences will be determined between the drug-free condition and the lidocaine condition. Higher values of d-prime indicate stronger memory performance; a positive difference for drug-free minus lidocaine condition would indicate the expected decrease in memory performance. |
| Motor Response Time Differences | 1 minute | Response times (in ms) after hearing a tone will be recorded and compared between the drug-free and Lidocaine condition, with the calculated difference in response times reported. Higher values will reflect slower responses, which are expected under the lidocaine condition. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine Subjects receiving lidocaine during the drug portion of the experiment. | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Lidocaine |
|---|---|
| Age, Continuous | 31.4 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition
The Z-score is calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Primary outcome is listed for the Right insula, but similar scores are calculated throughout the brain. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate stronger correlation between functional MRI signal change and the task timing, with positive values indicating increases in fMRI signal and negative Z-scores indicating decreases. Practically, higher positive Z-scores indicate increased brain activity and larger negative Z-scores indicate decreased brain activity. This outcome is reported as a number, as it is calculated using all the data across subjects combined into one statistical measure for the overall strength of difference in MRI signal change between two groups of data. Dispersion measures cannot be calculated for the summary Z-score.
Time frame: 4.5 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lidocaine | Brain Activation to Painful Stimulation Difference: Drug-free Condition Minus Lidocaine Condition | 3.6 Z-score |
p-value: 0.004Regression, Linear
Primary
Resting-state Functional Connectivity Difference: Drug-free Minus Lidocaine
Functional connectivity (FC) measures the correlation of MRI signal time-series between brain regions. Changes in FC reflect differences in brain state, in this case between drug-free and lidocaine conditions. The reported value is the FC change between the right insula and anterior cingulate. A T-statistic of 0 indicates no change; more positive scores mean stronger connectivity in the drug-free condition, and more negative scores mean stronger connectivity with lidocaine. This outcome is a number reflecting the overall magnitude of difference between two datasets, calculated in one summary statistic. Dispersion measures cannot be calculated for the T-statistic in this analysis framework.
Time frame: 8 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lidocaine | Resting-state Functional Connectivity Difference: Drug-free Minus Lidocaine | 3.25 T-statistic |
p-value: 0.081616t-test, 2 sided
Secondary
Memory Performance Difference, Drug-free Minus Lidocaine Condition
Performance on a short computer-based test of memory for visual pictures will be quantified using signal detection metric d-prime, reflecting ability (in standard deviation units) to detect previously-seen images from the background noise of previously un-seen images. Differences will be determined between the drug-free condition and the lidocaine condition. Higher values of d-prime indicate stronger memory performance; a positive difference for drug-free minus lidocaine condition would indicate the expected decrease in memory performance.
Time frame: 3 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lidocaine | Memory Performance Difference, Drug-free Minus Lidocaine Condition | 0.48 d-prime |
Secondary
Motor Response Time Differences
Response times (in ms) after hearing a tone will be recorded and compared between the drug-free and Lidocaine condition, with the calculated difference in response times reported. Higher values will reflect slower responses, which are expected under the lidocaine condition.
Time frame: 1 minute
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine | Motor Response Time Differences | 10 milliseconds | Standard Deviation 100 |
Secondary
Pain Intensity Score Difference, Drug-free Condition Minus Lidocaine Condition
Numerical rating scale (0-10) pain score difference, comparing drug-free to the steady-state dose of lidocaine. Higher pain scores indicate more pain; a positive difference between pain score during the drug-free condition minus the value during the lidocaine condition indicates pain reduction (a better outcome).
Time frame: 12 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine | Pain Intensity Score Difference, Drug-free Condition Minus Lidocaine Condition | 0.4 units on a scale | Standard Deviation 0.2 |