Abstract: Objective Postoperative pain leading to chronic pain and increased mortality poses a serious threat to public health.Preemptive analgesia,which involves administering analgesic drugs before nociceptive stimulation,can effectively reduce the incidence and severity of postoperative pain.Our previous research has demonstrated that dexmedetomidine (DEX) exhibits significant preemptive analgesic effects without adverse reactions such as respiratory depression.However,the spatiotemporal mechanisms underlying DEX's central analgesic action remain unclear.This study aims to combine linear oscillatory energy (PSD) and nonlinear pattern entropy (PE) to construct a multidimensional brain state assessment system to evaluate the spatiotemporal mechanisms of DEX's central analgesic effects. Methods Twenty patients scheduled for total knee arthroplasty under spinal anesthesia were enrolled.DEX preemptive analgesia was divided into three phases to investigate dynamic functional changes in brain-specific regions during different DEX administration stages:Phase 1(Non-dosing phase):Baseline EEG was recorded for 5 minutes after patient admission before DEX administration.Phase 2 (DEX phase):After spinal anesthesia,DEX was infused continuously at 1.5 μg/kg/h for 30 minutes.Phase 3 (Cease phase):Following DEX cessation,EEG was monitored for an additional hour.Power spectral density (PSD) and permutation entropy (PE) characteristics of EEG signals were compared across the three phases. Results PSD analysis revealed that DEX specifically modulates pain-related brain regions (ACC,PFC).Delta-band (0~4 Hz) power in ACC and PFC progressively increased across Non-dosing,DEX,and Cease phases (more pronounced in PFC),with significantly higher PSD in DEX and Cease phases (P<0.005),possibly due to DEX accumulation.Topographic maps showed a fronto-occipital gradient activation pattern,suggesting α2 receptor-mediated slow-wave synchronization in the prefrontal cortex.PE analysis demonstrated a concentration-dependent reduction in neural complexity in frontal and temporal lobes (most significant in PFC),while parietal and occipital regions remained stable.This confirms DEX selectively suppresses nonlinear dynamics in higher-order cortices for analgesia,without hemispheric lateralization. Conclusion DEX exerts dual analgesic effects by enhancing delta-band PSD in PFC/ACC while suppressing beta/gamma activity—slow-wave synchronization inhibits pain integration,while pathological high-frequency oscillations are reduced,with PFC being more sensitive due to high α2 receptor density;and selectively decreasing PE in frontal/temporal lobes (affecting pain-emotion processing) while preserving parietal/occipital stability.

Key words: Power spectral density, Permutation entropy, Dexmedetomidine, Preemptive analgesia, Spatiotemporal brain dynamics

摘要： 目的 术后痛且造成慢性痛、死亡率增加而严重危害公共健康。超前镇痛通过在伤害性刺激前使用镇痛药物,可有效降低术后痛的发生率和严重程度。本研究团队前期证实右美托咪定超前镇痛效果显著且无呼吸抑制等不良反应,但右美镇痛的中枢作用的时空机制尚不清楚。本研究拟将线性振荡能量(PSD)与非线性格局熵(PE)相结合,构建了多维度脑状态评估体系评估右美镇痛的中枢作用的时空机制。方法 本研究纳入拟行椎管内麻醉条件下全膝关节置换术患者20例。将DEX超前镇痛分为3个时相,旨在探究右美托咪定(DEX)给药不同阶段脑功能特异性区域的动态功能变化。Phase 1:未用右美时相(Non-dosing phase);即患者入室平静5分钟后,给与全脑64位脑电监测;Phase 2:右美超前镇痛时相(Dexmiditomide preexmptive,DEX phase)即在腰麻完成后,以1.5ug/kg/h速度持续输注右美30分钟;Phase 3:右美停止输注时相(Dexmiditomide cease,Cease phase)即停止右美输注,持续监测1小时。比较20例患者三个时相EEG的功率谱密度和排序熵特点。结果 研究基于功率谱密度(PSD)和排序熵(PE)分析,揭示了右美托咪定(DEX)对痛觉感知脑区(ACC、PFC)的特异性调控机制。PSD结果显示,ACC和PFC在Non-dosing、DEX及Cease三个阶段delta频段(0~4 Hz)功率呈梯度升高(PFC增幅更显著),且全频段PSD在DEX和Cease阶段显著高于Non-dosing阶段(P＜0.005),可能与DEX累积浓度相关。地形图显示DEX诱导的额枕梯度激活模式,提示前额叶α2受体介导的慢波同步化。PE分析表明,额颞叶神经活动复杂度随DEX浓度增加呈序贯性降低(PFC最显著),而顶枕叶保持稳定,证实DEX通过选择性抑制高阶皮层的非线性动力学实现镇痛,且无显著半球偏侧性。两者共同提示DEX通过调节额颞叶慢波振荡与神经集群协同性发挥特异性镇静作用。结论 DEX通过增强PFC/ACC的delta频段PSD并抑制beta/gamma活动实现双重镇痛:慢波同步化抑制痛觉整合,同时减少病理性高频振荡,PFC因高a2受体密度更敏感。其镇痛具有脑区特异性:选择性降低额颞叶排序熵而保持顶枕叶稳定,抑制高阶皮层痛觉情绪加工。

关键词: 功率谱密度, 排序熵, 右美托咪定, 超前镇痛, 大脑时空特征