• Keith M Vogt, Alex C Burlew, Marcus A Simmons, Sujatha N Reddy, Courtney N Kozdron, and James W Ibinson.
• Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: Keith.Vogt@Pitt.edu.
• Br J Anaesth. 2024 Oct 9.

IntroductionIntravenous lidocaine is increasingly used as a nonopioid analgesic, but how it acts in the brain is incompletely understood. We conducted a functional MRI study of pain response, resting connectivity, and cognitive task performance in volunteers to elucidate the effects of lidocaine at the brain-systems level.MethodsWe enrolled 27 adults (age 22-55 yr) in this single-arm, open-label study. Pain response task and resting-state functional MRI scans at 3 T were obtained at baseline and then with a constant effect-site concentration of lidocaine. Electric nerve stimulation, titrated in advance to 7/10 intensity, was used for the pain task (five times every 10 s). Group-level differences in pain task-evoked responses (primary outcome, focused on the insula) and in resting connectivity were compared between baseline and lidocaine conditions, using adjusted P<0.05 to account for multiple comparisons. Pain ratings and performance on a brief battery of computer-based tasks were also recorded.ResultsLidocaine infusion was associated with decreased pain-evoked responses in the insula (left: Z=3.6, P<0.001, right: Z=3.6, P=0.004) and other brain areas including the cingulate gyrus, thalamus, and primary sensory cortex. Resting-state connectivity showed significant diffuse reductions in both region-to-region and global connectivity measures with lidocaine. Small decreases in pain intensity and unpleasantness and worse memory performance were also seen with lidocaine.ConclusionsLidocaine was associated with broad reductions in functional MRI response to acute pain and modulated whole-brain functional connectivity, predominantly decreasing long-range connectivity. This was accompanied by small but significant decreases in pain perception and memory performance.Clinical Trial RegistrationNCT05501600.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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