Neural correlates of systemic lidocaine administration in healthy adults measured by functional MRI: a single arm open label study.

Introduction: Intravenous 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.

Methods: We 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.

Results: Lidocaine 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.

Conclusions: Lidocaine 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 registration: NCT05501600.