1-甲基海因对慢性疼痛大鼠钠离子通道蛋白Nav1.8的干预作用

doi:10.11843/j.issn.0366-6964.2023.12.039

畜牧兽医学报 ›› 2023, Vol. 54 ›› Issue (12): 5312-5317.doi: 10.11843/j.issn.0366-6964.2023.12.039

1-甲基海因对慢性疼痛大鼠钠离子通道蛋白Nav1.8的干预作用

梁雾滢^1,2,3, 刘镇^1,2,3, 曾玉淇^1,2,3, 吕俊瑾^1,2,3, 莫睿文^1,2,3, 远立国^1,2,3*

1. 华南农业大学兽医学院, 广州 510642;
2. 广东省兽医临床重大疾病综合防控重点实验室, 广州 510642;
3. 广东省宠物工程技术研究中心, 广州 510642

收稿日期:2023-05-09 出版日期:2023-12-23 发布日期:2023-12-26
通讯作者: 远立国,主要从事兽医外科研究,E-mail:yuanliguo@scau.edu.cn
作者简介:梁雾滢(1998-),女,广东佛山人,硕士生,主要从事兽医外科研究,Email:liangwuying@stu.scau.edu.cn;刘镇(1993-),江西南昌人,硕士,主要从事兽医外科研究,E-mail:altmanliu@stu.scau.edu.cn。
基金资助:
广东省自然科学基金(2013B040200032)

Effect of 1-methylhydantoin on Sodium Channel Nav1.8 in Rats with Chronic Pain

LIANG Wuying^1,2,3, LIU Zhen^1,2,3, ZENG Yuqi^1,2,3, Lü Junjin^1,2,3, MO Ruiwen^1,2,3, YUAN Liguo^1,2,3*

1. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China;
2. Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou 510642, China;
3. Guangdong Technological Engineering Research Center for Pets, Guangzhou 510642, China

Received:2023-05-09 Online:2023-12-23 Published:2023-12-26

摘要/Abstract

摘要： 旨在研究1-甲基海因(1-methylhydantoin, MH)对钠离子通道(Nav channels, Navs)1.8的干预作用,为临床科学治疗疼痛提供理论依据,为实现"疼痛最小化"终极目标拓宽途径。选取60只SPF级SD大鼠通过随机分组设计,各组分别使用1-甲基海因(MH组)、利多卡因(L组)、氨溴索(A组)处理,第21和28天使用蛋白免疫印记法检测大鼠L4~L6段背根神经节(dorsal root ganglia, DRG)Nav1.8的蛋白表达,采用全细胞膜片钳技术检测MH作用下的Nav1.8通道峰电流。结果表明,与M组相比,MH能使Nav1.8表达显著下降(P<0.05)。MH对Nav1.8通道峰电流具有一定抑制作用,10和100 μmol·L ^-1 MH对Nav1.8的电流抑制率分别为6.34%±3.13%和14.6%±1.52%,具有量效关系。提示MH能够下调慢性疼痛大鼠DRG中Nav1.8的表达,同时抑制Nav1.8电流,进而产生镇痛作用。

关键词: 1-甲基海因, 大鼠, 慢性疼痛, Nav1.8, 膜片钳技术

Abstract: The purpose of this study is to investigate the effect of 1-methylhydantoin on Nav Channels 1.8, which can provide a theoretical basis for pain intervened and different ways to achieve the ultimate goal of "pain minimization". Sixty SPF SD rats were randomly divided into six groups.The group was treated with 1-methylhyne (group MH), lidocaine (group L) and ambroxol (group A), respectively. On the 21st and 28th day after modeling, Western blot was used to detect the protein expressions of Nav1.8 in the L4-L6 dorsal root ganglia of rats, and patch-clamp technique was used to detect the peak currents of Nav1.8 channels under the effect of MH. Comparing with the group of model,the results showed that MH could decrease the expression of Nav1.8 significantly (P<0.05). MH inhibited the channel peak currents of Nav1.8 to a certain extent. The current inhibition rates of 10 μmol·L^-1 and 100 μmol·L^-1 MH to Nav1.8 were 6.34%±3.13% and 14.6%±1.52% respectively, which is showing a dose-response relationship. It is suggested that MH can decrease the expression of Nav1.8 in DRG of rats with chronic pain, and inhibit Nav1.8 current at the same time, thus producing analgesic.

Key words: 1-methylhydantoin, rat, chronic pain, Nav1.8, patch-clamp technique

中图分类号:

S859.791

梁雾滢, 刘镇, 曾玉淇, 吕俊瑾, 莫睿文, 远立国. 1-甲基海因对慢性疼痛大鼠钠离子通道蛋白Nav1.8的干预作用[J]. 畜牧兽医学报, 2023, 54(12): 5312-5317.

LIANG Wuying, LIU Zhen, ZENG Yuqi, Lü Junjin, MO Ruiwen, YUAN Liguo. Effect of 1-methylhydantoin on Sodium Channel Nav1.8 in Rats with Chronic Pain[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(12): 5312-5317.

参考文献

[1] CHAPMAN C R, VIERCK C J. The transition of acute postoperative pain to chronic pain: an integrative overview of research on mechanisms[J]. J Pain, 2017, 18(4):359. e1-359. e38.
[2] GLARE P, AUBREY K R, MYLES P S. Transition from acute to chronic pain after surgery[J]. Lancet, 2019, 393(10180):1537-1546.
[3] 刘燕. 电针对神经病理性疼痛大鼠疼痛及抑郁的作用机制研究[D]. 泸州:西南医科大学, 2021.LIU Y. Effect and mechanism of electroacupuncture on pain and depression in rats of neuropathic pain[D]. Luzhou:Southwest Medical University, 2021. (in Chinese)
[4] YEKKIRALA A S, ROBERSON D P, BEAN B P, et al. Breaking barriers to novel analgesic drug development[J]. Nat Rev Drug Discov, 2017, 16(8):545-564.
[5] JI R R, NACKLEY A, HUH Y, et al. Neuroinflammation and central sensitization in chronic and widespread pain[J]. Anesthesiology, 2018, 129(2):343-366.
[6] DIB-HAJJ S D, GEHA P, WAXMAN S G. Sodium channels in pain disorders:pathophysiology and prospects for treatment[J]. Pain, 2017, 158(Suppl 1):S97-S107.
[7] BENNETT D L, CLARK A J, HUANG J Y, et al. The role of voltage-gated sodium channels in pain signaling[J]. Physiol Rev, 2019, 99(2):1079-1151.
[8] 朱谦, 樊碧发, 张达颖, 等. 周围神经病理性疼痛诊疗中国专家共识[J]. 中国疼痛医学杂志, 2020, 26(5):321-328.ZHU Q, FAN B F, ZHANG D Y, et al. Experts consuses on diagnosis and treat of neuropathic pain[J]. Chinese Journal of Pain Medicine, 2020, 26(5):321-328. (in Chinese)
[9] 康道林, 杨雪, 赵娟, 等. Nav1. 8通道在部分神经损伤大鼠背根神经节及外周神经的表达[J]. 广西医学, 2019, 41(14):1803-1807. KANG D L, YANG X, ZHAO J, et al. Expression of Nav1. 8 channel in dorsal root ganglion and peripheral nerves of spared nerve injury rats[J]. Guangxi Medical Journal, 2019, 41(14):1803-1807. (in Chinese)
[10] 羊健, 杨清云, 孙水根, 等. 电压门控钠通道在慢性疼痛药物发现中的研究进展[J]. 安徽医药, 2023, 27(1):5-9.YANG J, YANG Q Y, SUN S G, et al. Research progress of voltage-gated sodium channels in drug discovery for chronic pain[J]. Anhui Medical and Pharmaceutical Journal, 2023, 27(1):5-9. (in Chinese)
[11] JI G C, ZHOU S T, SHAPIRO G, et al. Erratum to "analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: in vitro and in vivo studies in rat"[Pain 124(2006) 34-49][J]. Pain, 2006, 125(3):296.
[12] SCHLERETH T. Guideline "diagnosis and non interventional therapy of neuropathic pain" of the German society of neurology (deutsche Gesellschaft für Neurologie)[J]. Neurol Res Pract, 2020, 2:16.
[13] YANG Y, MIS M A, ESTACION M, et al. Nav 1.7 as a pharmacogenomic target for pain:moving toward precision medicine[J]. Trends Pharmacol Sci, 2018, 39(3):259-275.
[14] BENNETT G J, XIE Y K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man[J]. Pain, 1988, 33(1):87-107.
[15] EKBERG J, ADAMS D J. Neuronal voltage-gated sodium channel subtypes:key roles in inflammatory and neuropathic pain[J]. Int J Biochem Cell Biol, 2006, 38(12):2005-2010.
[16] STRICKLAND I T, MARTINDALE J C, WOODHAMS P L, et al. Changes in the expression of Nav1. 7, Nav1. 8 and Nav1. 9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain[J]. Eur J Pain, 2008, 12(5):564-572.
[17] 程凯, 陈前, 袁慧伦, 等. 益气活血通络方联合针刺对糖尿病神经病理性疼痛大鼠背根神经节Nav1. 7和Nav1. 8表达的影响[J]. 安徽中医药大学学报, 2023, 42(3):42-47. CHENG K, CHEN Q, YUAN H L, et al. Effect of Yiqi huoxue tongluo prescription combined with acupuncture on the expression of Nav1. 7 and Nav1. 8 in the dorsal root ganglia of rats with diabetic neuropathic pain[J]. Journal of Anhui University of Chinese Medicine, 2023, 42(3):42-47. (in Chinese)
[18] LOLIGNIER S, AMSALEM M, MAINGRET F, et al. Nav1.9 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation[J]. PLoS One, 2011, 6(8):e23083.
[19] 李笑笑, 陈涵, 李妍妍, 等. Nav1.7、Nav1.8和交感芽生在大鼠SNI模型神经病理性疼痛形成过程中的作用[J]. 复旦学报:医学版, 2023, 50(1):57-63. LI X X, CHEN H, LI Y Y, et al. Roles of Nav1. 7, Nav1. 8 and sympathetic sprouting in neuropathic pain of rat SNI model[J]. Fudan University Journal of Medical Sciences, 2023, 50(1):57-63. (in Chinese)
[20] SUN J F, XU Y J, KONG X H, et al. Fenamates inhibit human sodium channel Nav1. 7 and Nav1.8[J]. Neurosci Lett, 2019, 696:67-73.
[21] 董黎颖. 新型芳基磺酰胺类Nav1.7通道抑制剂的镇痛作用及机制研究[D]. 青岛:青岛大学, 2022.DONG L Y. Antinociception and mechanism of a novel arylsulfonamide Nav1.7 channel inhibitors[D]. Qingdao: Qingdao University, 2022. (in Chinese)

1-甲基海因对慢性疼痛大鼠钠离子通道蛋白Nav1.8的干预作用

Effect of 1-methylhydantoin on Sodium Channel Nav1.8 in Rats with Chronic Pain

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