Chen Rui, Liu Yiran, Qian Liu, Yi Mingliang, Yin Hong, Wang Shun, Xiang Bingbing
Department of Anesthesiology, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China.
Nursing Department, Cujin Community Health Service Center, Chengdu, China.
Front Pharmacol. 2025 Mar 26;16:1573254. doi: 10.3389/fphar.2025.1573254. eCollection 2025.
Voltage-gated sodium channels, especially the Nav1.7, Nav1.8, and Nav1.9 subtypes, play a crucial role in the transmission of pain signals. Nav1.7 is considered a threshold channel that regulates the generation of action potentials and is closely associated with various hereditary pain disorders. Nav1.8 primarily participates in inflammatory and neuropathic pain within the peripheral nervous system. Its characteristic of not involving the central nervous system makes it a potential target for non-addictive analgesics. Nav1.9 has shown significant involvement in cold pain sensing and small fiber neuropathy, although its mechanism of action is still under further investigation. Currently, despite promising results from preclinical studies, sodium channel inhibitors have not fully met expectations in clinical trials due to issues such as drug selectivity, dosing, and safety. The development of Nav1.7 and Nav1.8 inhibitors faces challenges such as drug intolerance, insufficient target occupancy, and off-target side effects. Future research may promote the development of non-opioid analgesics through combined inhibition strategies targeting multiple Nav subtypes, as well as improving drug selectivity and bioavailability. Overall, sodium channel inhibitors remain a key area of research in pain management, but their clinical application prospects still require further exploration.
电压门控钠通道，尤其是Nav1.7、Nav1.8和Nav1.9亚型，在疼痛信号的传递中起着至关重要的作用。Nav1.7被认为是一种调节动作电位产生的阈值通道，与多种遗传性疼痛疾病密切相关。Nav1.8主要参与外周神经系统中的炎症性和神经性疼痛。其不涉及中枢神经系统的特性使其成为非成瘾性镇痛药的潜在靶点。Nav1.9已显示出在冷痛觉和小纤维神经病变中起重要作用，尽管其作用机制仍在进一步研究中。目前，尽管临床前研究取得了有前景的结果，但由于药物选择性、给药剂量和安全性等问题，钠通道抑制剂在临床试验中尚未完全达到预期。Nav1.7和Nav1.8抑制剂的开发面临着药物不耐受、靶点占有率不足和脱靶副作用等挑战。未来的研究可能通过针对多种Nav亚型的联合抑制策略，以及提高药物选择性和生物利用度，来促进非阿片类镇痛药的开发。总体而言，钠通道抑制剂仍然是疼痛管理研究的关键领域，但其临床应用前景仍需进一步探索。
