激光生物学报, 2020, 29 (6): 496, 网络出版: 2021-02-05  

钠通道NaV1.9与疼痛的研究进展

Research Progress of Sodium Channel NaV1.9 and Pain
何询 1,*周熙 2
作者单位
1 深圳未名新鹏生物医药有限公司,深圳 518057
2 湖南师范大学生命科学学院动物多肽药物创制国家地方联合工程实验室,长沙 410081
摘要
电压门控钠通道 NaV1.9特异性表达于外周伤害感受器,在神经电信号产生和传导的过程中扮演着重要角色。动物模型和临床遗传学研究表明,其在炎性疼痛、神经性疼痛和冷痛中具有重要作用,是一个潜在的镇痛药物研发靶点。本文从 NaV1.9的表达定位、生理学特性、疼痛动物模型研究、临床相关疼痛疾病研究和药理学研究这几个方面对 NaV1.9与疼痛关系进行综述,探讨靶向镇痛药物开发,为深入研究 Nav1.9在疼痛中的重要角色提供参考。
Abstract
Voltage-gated sodium channel NaV1.9 is preferentially expressed in peripheral nociceptors and plays an impor-tant role in the generation and propagation of electrical signals in nerves. Animal models and genetic studies have shown that it plays a major role in in.ammatory pain, neuropathic pain and cold allodynia. Therefore, NaV1.9 is a potential target for an-algesics. Here, we review recent studies that reveal the relationship between NaV1.9 and pain. NaV1.9’s expression location, physiological characteristics, animal models, genetic validation in humans and pharmacological study, and the development of targeted analgesics were discussed, to provide reference for the further research of the role of NaV1.9 in pain.
参考文献

[1] TREEDE R D. The international association for the study of pain definition of pain: as valid in 2018 as in 1979,but in need of regularly updated footnotes[J]. Pain Reports, 2018, 3(2): e643.

[2] HYLANDS-WHITE N, DUARTE R V, RAPHAEL J H. An over-view of treatment approaches for chronic pain management[J]. Rheumatology International, 2017, 37(1): 29-42.

[3] BENNETT D L, CLARK A J, HUANG J, et al. The role of volt-age-gated sodium channels in pain signaling[J]. Physiological Reviews, 2019, 99(2): 1079-1151.

[4] ZAKRZEWSKA J M, PALMER J, MORISSET V, et al. Safety and e.cacy of a NaV1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial[J]. The Lancet Neurology, 2017, 16(4): 291-300.

[5] KINGWELL K. NaV1.7 withholds its pain potential[J]. Nature Reviews Drug Discovery, 2019, 18: 321-323.

[6] DIB-HAJJ S D, BLACK J A, WAXMAN S G. NaV1.9: a sodium channel linked to human pain[J]. Nature Reviews Neuroscience, 2015, 16(9): 511-519.

[7] DIB-HAJJ S, BLACK J A, CUMMINS T R, et al. NaN/NaV1.9: a sodium channel with unique properties[J]. Trends in Neurosci-ences, 2002, 25(5): 253-259.

[8] LIN Z, SANTOS S, PADILLA K, et al. Biophysical and pharma-cological characterization of NaV1.9 voltage dependent sodium channels stably expressed in HEK-293 cells[J]. PLoS One, 2016,11(8): e0161450.

[9] LIU C J, DIB-HAJJ S D, BLACK J A, et al. Direct interaction with contactin targets voltage-gated sodium channel NaV1.9/NaN to the cell membrane[J]. The Journal of Biological Chemistry, 2001, 276(49): 46553-46561.

[10] HERZOG R I, CUMMINS T R, WAXMAN S G. Persistent ttx-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons[J]. Journal of Neurophysiology, 2001, 86(3): 1351-1364.

[11] PRIEST B T, MURPHY B A, LINDIA J A, et al. Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior[J]. Proceedings of the National Academy of Sciences of the United States of America,2005, 102(26): 9382-9387.

[12] YUYQ, ZHAOF,GUAN SM, et al. Antisense-mediated knock-down of NaV1.8, but not NaV1.9, generates inhibitory effects on complete freund’s adjuvant-induced in.ammatory pain in rat[J]. PLoS One, 2011, 6(5): e19865.

[13] MAINGRET F, COSTE B, PADILLA F, et al. Inflammatory mediators increase NaV1.9 current and excitability in nociceptors through a coincident detection mechanism[J]. The Journal of General Physiology, 2008, 131(3): 211-225.

[14] AMSALEM M, POILBOUT C, FERRACCI G, et al. Membrane cholesterol depletion as a trigger of NaV1.9 channel-mediated in-.ammatory pain[J]. The EMBO Journal, 2018, 37(8): e97349.

[15] LUIZ A P, KOPACH O, SANTANA-VARELA S, et al. The role of NaV1.9 channel in the development of neuropathic orofacial pain associated with trigeminal neuralgia[J]. Molecular Pain, 2015,25(11): 72.

[16] BONNET C, HAO J, OSORIO N, et al. Maladaptive activation of NaV1.9 channels by nitric oxide causes triptan-induced medica-tion overuse headache[J]. Nature Communications, 2019, 10(1): 4253.

[17] LOLIGNIER S, BONNET C, GAUDIOSO C, et al. The NaV1.9 channel is a key determinant of cold pain sensation and cold allo-dynia[J]. Cell Reports, 2015, 11(7): 1067-1078.

[18] QIU F, JIANG Y, ZHANG H, et al. Increased expression of tetrodotoxin-resistant sodium channels NaV1.8 and NaV1.9 within dorsal root ganglia in a rat model of bone cancer pain[J]. Neuro-science Letters, 2012, 512(2): 61-66.

[19] LEIPOLD E, LIEBMANN L, KORENKE G C, et al. A de novo gain-of-function mutation in SCN11A causes loss of pain percep-tion[J]. Nature Genetics, 2013, 45(11): 1399-1404.

[20] ZHANG X Y, WEN J, YANG W, et al. Gain-of-function mutations in SCN11A cause familial episodic pain[J]. American Journal of Human Genetics, 2013, 93(5): 957-966.

[21] HUANG J, HAN C, ESTACION M, et al. Gain-of-function muta-tions in sodium channel NaV1.9 in painful neuropathy[J]. Brain, 2014, 137(6): 1627-1642.

[22] SALVATIERRA J, DIAZ-BUSTAMANTE M, MEIXIONG J, et al. A disease mutation reveals a role for NaV1.9 in acute itch[J]. The Journal of Clinical Investigation, 2018, 128(12): 5434-5447.

[23] ZHOU X, XIAO Z, XU Y, et al. Electrophysiological and phar-macological analyses of NaV1.9 voltage-gated sodium channel by establishing a heterologous expression system[J]. Frontiers in Pharmacology, 2017, 22(8): 852.

[24] ZHOU X, MA T, YANG L, et al. Spider venom-derived peptide induces hyperalgesia in NaV1.7 knockout mice by activating NaV1.9 channels[J]. Nature Communications, 2020, 11(1): 2293.

[25] LIANG J, LIU X, ZHENG J, et al. Effect of amitriptyline on tetrodotoxin-resistant NaV1.9 currents in nociceptive trigeminal neurons[J]. Molecular Pain, 2013, 22(9): 31.

[26] BLACK J A, VASYLYEV D, DIB-HAJJ S D, et al. NaV1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus[J]. Experimental Neurology, 2014, 253: 174-179.

[27] CARINE C, NANCY O, MARCEL C, et al. Activation of neuroki-nin 3 receptor increases NaV1.9 current in enteric neurons[J]. The Journal of Physiology, 2009, 587(7): 1461-1479.

何询, 周熙. 钠通道NaV1.9与疼痛的研究进展[J]. 激光生物学报, 2020, 29(6): 496. HE Xun, ZHOU Xi. Research Progress of Sodium Channel NaV1.9 and Pain[J]. Acta Laser Biology Sinica, 2020, 29(6): 496.

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