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.

中文翻译：

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通过功能性 MRI 测量健康成人全身性利多卡因给药的神经相关性：一项单臂开放标签研究。


引言 静脉注射利多卡因越来越多地用作非阿片类镇痛药，但尚不清楚它在大脑中的作用。我们对志愿者的疼痛反应、静息连接和认知任务表现进行了功能性 MRI 研究，以阐明利多卡因在大脑系统水平上的影响。方法 我们在这项单臂、开放标签研究中招募了 27 名成年人 （年龄 22-55 岁）。在基线时获得 3 T 的疼痛反应任务和静息态功能性 MRI 扫描，然后以恒定的效果部位浓度获得利多卡因。提前滴定至 7/10 强度的神经电刺激用于疼痛任务（每 10 秒 5 次）。使用调整后的 P<0.05 比较基线和利多卡因条件之间疼痛任务诱发反应 （主要结果，集中在岛叶） 和静息连接的组级差异，以解释多重比较。还记录了一系列简短的基于计算机的任务的疼痛评分和表现。结果 利多卡因输注与岛叶 （左：Z=3.6，P<0.001，右：Z=3.6，P=0.004） 和其他脑区（包括扣带回、丘脑和初级感觉皮层）的疼痛诱发反应减少有关。静息态连接性显示利多卡因的区域间和全球连接测量均显著弥漫性降低。利多卡因的疼痛强度和不愉快程度也略有下降，记忆力也较差。结论 利多卡因与功能性 MRI 对急性疼痛的反应的广泛降低和全脑功能连接性调节相关，主要降低远程连接性。这伴随着疼痛感知和记忆表现的小幅但显着下降。 临床试验注册 NCT05501600。