Utugi Syogo, Sashide Yukito, Takeda Mamoru
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara 252-5201, Japan.
Metabolites. 2025 Jul 1;15(7):439. doi: 10.3390/metabo15070439.
Given the side effects and reduced efficacy of conventional local anesthetics in inflammatory conditions, there is a compelling need for complementary alternative medicine (CAM), particularly those based on phytochemicals. While a previous study showed that in vivo local injection of (-)-epigallocatechin-3-gallate (EGCG) into the peripheral receptive field suppresses the excitability of rat trigeminal ganglion (TG) neurons in the absence of inflammation, the acute effects of EGCG in vivo, especially on TG neurons under inflammatory conditions, are still unknown. We aimed to determine if acute local EGCG administration into inflamed tissue effectively attenuates the excitability of nociceptive TG neurons evoked by mechanical stimulation. The escape reflex threshold was measured to assess hyperalgesia caused by complete Freund's adjuvant (CFA)-induced inflammation. To assess neuronal activity, extracellular single-unit recordings were performed on TG neurons in anesthetized CFA-inflamed rats in response to orofacial mechanical stimulation. The mechanical escape threshold was significantly lower in CFA-inflamed rats compared to before CFA injection. EGCG (1-10 mM) reversibly and dose-dependently inhibited the mean firing frequency of TG neurons evoked by both non-noxious and noxious mechanical stimuli ( < 0.05). For comparison, 1% lidocaine (37 mM), a local anesthetic, also caused reversible inhibition of the mean firing frequency in inflamed TG neurons responding to mechanical stimuli. Importantly, 10 mM EGCG produced a significantly greater magnitude of inhibition on TG neuronal discharge frequency than 1% lidocaine (noxious, lidocaine vs. EGCG, 19.7 ± 3.3% vs. 42.3 ± 3.4%, < 0.05). Local injection of EGCG into inflamed tissue effectively suppresses the excitability of nociceptive primary sensory TG neurons, as indicated by these findings. Significantly, locally administered EGCG exerted a more potent local analgesic action compared to conventional voltage-gated sodium channel blockers. This heightened efficacy originates from EGCG's ability to inhibit both generator potentials and action potentials directly at nociceptive primary nerve terminals. As a result, EGCG stands out as a compelling candidate for novel analgesic development, holding particular relevance for CAM strategies.
鉴于传统局部麻醉药在炎症状态下存在副作用且疗效降低，因此迫切需要补充替代医学（CAM），尤其是基于植物化学物质的替代医学。虽然先前的一项研究表明，在无炎症情况下，将（-）-表没食子儿茶素-3-没食子酸酯（EGCG）体内局部注射到外周感受野可抑制大鼠三叉神经节（TG）神经元的兴奋性，但EGCG在体内的急性作用，尤其是在炎症条件下对TG神经元的作用，仍然未知。我们旨在确定将EGCG急性局部给药至炎症组织是否能有效减弱机械刺激诱发的伤害性TG神经元的兴奋性。测量逃避反射阈值以评估由完全弗氏佐剂（CFA）诱导的炎症引起的痛觉过敏。为了评估神经元活动，在麻醉的CFA炎症大鼠中对TG神经元进行细胞外单单位记录，以响应口面部机械刺激。与CFA注射前相比，CFA炎症大鼠的机械逃避阈值显著降低。EGCG（1-10 mM）可逆且剂量依赖性地抑制由非伤害性和伤害性机械刺激诱发的TG神经元的平均放电频率（P<0.05）。作为比较，1%利多卡因（37 mM），一种局部麻醉药，也可对响应机械刺激的炎症TG神经元的平均放电频率产生可逆抑制。重要的是，10 mM EGCG对TG神经元放电频率的抑制幅度明显大于1%利多卡因（伤害性刺激，利多卡因与EGCG相比，19.7±3.3%对42.3±3.4%，P<0.05）。这些发现表明，将EGCG局部注射到炎症组织中可有效抑制伤害性初级感觉TG神经元的兴奋性。值得注意的是，与传统的电压门控钠通道阻滞剂相比，局部给药的EGCG具有更强的局部镇痛作用。这种增强的疗效源于EGCG能够直接在伤害性初级神经末梢抑制发生器电位和动作电位。因此，EGCG是新型镇痛药开发的一个有吸引力的候选药物，对补充替代医学策略具有特别重要的意义。
