Neural Correlates of Lidocaine Analgesia

Phase 1

Completed

Conditions: Anesthesia
Pain

Interventions: Device: Peripheral Nerve Stimulation
Drug: Lidocaine IV

Registration Number: NCT05501600

Lead Sponsor: Keith M Vogt

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Exclusion Criteria

Pregnancy
Body mass index > 40
Having moderate to severe sleep apnea
Having chronic pain requiring the regular use of pain medicine 3 or more times per week
Having neurologic or psychiatric disease, including benign tremor, anxiety, and depression
Having a history of seizures
Having history of cardiac rhythm disturbance (such as heart block, or atrial fibrillation)
Being severely claustrophobic
Having metal implants or non-removable metal piercings
Having metal-containing tattoos, particularly on the face
Having a history of adverse reaction to lidocaine
Are regularly taking: antiepileptics, antidepressants, anti-psychotics, anti-anxiety medication, stimulants, sleep-aids, or pain medication
Are taking prescribed medications for psychiatric or neurological conditions
Having hypersensitivity to lidocaine or to any other local anesthetics of the amide type
Having Wolff-Parkinson-White syndrome
Having known renal or hepatic dysfunction
having glucose-6-phosphate dehydrogenase deficiency or history of methemoglobinemia

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lidocaine	Peripheral Nerve Stimulation	Subjects will receive lidocaine during the drug portion of the experiment.
Lidocaine	Lidocaine IV	Subjects will receive lidocaine during the drug portion of the experiment.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.