NaV1.8抑制与非阿片类镇痛在耳鼻咽喉科的未来：一项叙述性综述

文献信息

中文摘要

重要性： 耳鼻咽喉科术后疼痛管理需要在有效镇痛与尽量减少不良反应（如阿片类药物相关并发症）之间取得平衡。Suzetrigine是一种首创的选择性电压门控钠通道（NaV1.8）抑制剂，最近已获美国食品药品监督管理局批准。Suzetrigine选择性抑制表达于外周伤害性神经元上的NaV1.8通道，从而减少疼痛信号传导，且不产生与阿片类药物相关的呼吸抑制、镇静或滥用潜力。本综述总结了suzetrigine的药理学、疗效、安全性特征、局限性及其在耳鼻咽喉科的潜在应用。
观察： 前瞻性临床试验包括2项2期随机临床试验、2项3期随机安慰剂对照试验和1项3期开放标签研究，涉及超过3000例患者。在腹壁成形术和拇外翻切除术疼痛模型中，suzetrigine显示出优于安慰剂的镇痛效果，以及与氢可酮/对乙酰氨基酚相当的混合疗效。该药物总体耐受性良好，不良事件发生率与安慰剂相似，未报告显著的呼吸、心脏或镇静相关不良反应。此外，1项回顾性队列研究报告了其在接受游离皮瓣重建和经口机器人手术患者中的结果。
结论与意义： Suzetrigine是一种有前景的非阿片类镇痛药，在急性术后疼痛中显示出优于安慰剂的疗效，并具有良好的安全性特征。在耳鼻咽喉科，suzetrigine可作为多模式镇痛的辅助手段，并为存在传统镇痛药禁忌证、阿片类药物使用障碍或预计阿片类药物使用量较高的手术（如扁桃体切除术、睡眠手术和重大头颈手术）患者提供减少阿片类药物使用的选择。有必要在耳鼻咽喉科开展未来研究，以评估suzetrigine能否在不影响镇痛效果的情况下显著减少术后阿片类药物暴露。

英文摘要

IMPORTANCE: Postoperative pain management in otolaryngology requires balancing effective analgesia while minimizing adverse effects, such as opioid-related complications. Suzetrigine is a first-in-class selective voltage-gated sodium channel (NaV1.8) inhibitor that has been recently approved by the US Food and Drug Administration. Suzetrigine selectively inhibits NaV1.8 channels expressed in peripheral nociceptive neurons, thereby reducing pain signaling without the respiratory depression, sedation, or misuse potential associated with opioids. This review summarizes the pharmacology, efficacy, safety profile, limitations, and potential applications of suzetrigine in otolaryngology.
OBSERVATIONS: Prospective clinical trials consist of 2 phase 2 randomized clinical trials, 2 phase 3 randomized placebo-controlled trials, and 1 phase 3 open-label study involving more than 3000 patients. Across abdominoplasty and bunionectomy pain models, suzetrigine demonstrated superior analgesia compared with placebo and mixed efficacy comparable to hydrocodone/acetaminophen. The drug was generally well tolerated, with adverse event rates similar to placebo and no significant respiratory, cardiac, or sedating adverse effects reported. Additionally, 1 retrospective cohort study has reported results in patients undergoing free flap reconstruction and transoral robotic surgery.
CONCLUSIONS AND RELEVANCE: Suzetrigine is a promising nonopioid analgesic with demonstrated efficacy compared to placebo in acute postoperative pain and a favorable safety profile. In otolaryngology, suzetrigine may serve as an adjunct to multimodal analgesia and an opioid-sparing option for patients with contraindications to traditional analgesics, opioid use disorder, or procedures that are expected to have high opioid utilization such as tonsillectomy, sleep surgery, and major head and neck surgery. Future studies in otolaryngology are warranted to evaluate whether suzetrigine can meaningfully reduce postoperative opioid exposure without compromising analgesic effectiveness.