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中华诊断学电子杂志 ›› 2017, Vol. 05 ›› Issue (03) : 205 -209. doi: 10.3877/cma.j.issn.2095-655X.2017.03.016

所属专题: 文献

基础研究

慢性神经根痛大鼠背根神经节KCNQ通道表达及功能改变
李雷1,(), 张越2   
  1. 1. 272067 济宁医学院诊断学教研室
    2. 272100 济宁市第一人民医院保健病房
  • 收稿日期:2017-02-20 出版日期:2017-08-26
  • 通信作者: 李雷
  • 基金资助:
    山东省自然科学基金(ZR2014HL038); 济宁医学院青年基金(JYQ14KJ25)

Expression and functional changes of KCNQ channels in the chronic compression of dorsal root ganglion model

Lei Li1,(), Yue Zhang2   

  1. 1. Department of Diagnosis, Jining Medical University, Jining 272067, China
    2. Department of Board of Health, the first People′s Hospital of Jining, Jining 272100, China
  • Received:2017-02-20 Published:2017-08-26
  • Corresponding author: Lei Li
  • About author:
    Corresponding author: Li Lei, Email:
引用本文:

李雷, 张越. 慢性神经根痛大鼠背根神经节KCNQ通道表达及功能改变[J]. 中华诊断学电子杂志, 2017, 05(03): 205-209.

Lei Li, Yue Zhang. Expression and functional changes of KCNQ channels in the chronic compression of dorsal root ganglion model[J]. Chinese Journal of Diagnostics(Electronic Edition), 2017, 05(03): 205-209.

目的

探讨慢性神经根痛模型(CCD)SD大鼠KCNQ通道表达和功能的改变。

方法

CCD SD大鼠及假手术组大鼠分别用von Frey纤维检测触觉痛觉阈值。用荧光实时定量聚合酶链反应(PCR)检测SD大鼠背根神经节(DRG)组织KCNQ2/3/5 mRNA表达,用蛋白印迹检测DRG组织KCNQ2/3/5蛋白表达。用全细胞膜片钳的电压钳检测DRG神经元M电流密度。

结果

CCD SD大鼠表现出明显的触觉痛觉阈值下降[(4.02±1.06)g,(13.31±1.54)g;t=20.46,P<0.01]。CCD SD大鼠背根神经节组织KCNQ2/3/5 mRNA及蛋白表达下降,伴随背根神经节神经元M电流密度下降[(5.58±1.34)pA/pF,(7.91±1.52)pA/pF;t=4.62,P<0.01]。KCNQ通道开放剂瑞替加滨灌胃可以减轻CCD SD大鼠的触觉痛觉过敏症状[(6.22±1.52)g,(3.90±1.14)g;t=2.57,P<0.05]。

结论

CCD SD大鼠DRG神经元KCNQ通道表达下调引起的M电流密度降低可能是触觉痛觉过敏症状的原因;瑞替加滨通过增加CCD SD大鼠DRG神经元M电流密度起到减轻触觉痛觉过敏的作用。

Objective

To explore the changes of expression and activity of the KCNQ channels in the chronic compression of dorsal root ganglion (CCD) of SD rats model.

Methods

The von Frey filaments were used to assess pain threshold of CCD rats and the control rats.Real-time polymerase chain reaction (PCR) was performed to determine KCNQ2/3/5 mRNA expression of dorsal root ganglion(DRG) tissue.Western blot assay was used to measure KCNQ2/3/5 protein expression.Whole-cell voltage clamp was used to determine M current density of DRG neurons.

Results

CCD rats showed pronounced hyperalgesia behaviors to noxious mechanical stimulation [(4.02±1.06)g, (13.31±1.54)g; t=20.46, P<0.01]. The mRNA and protein levels of KCNQ2/3/5 of DRG tissue notably decreased, followed with the reduction of M current density in DRG neurons of CCD rats [(5.58±1.34)pA/pF, (7.91±1.52)pA/pF; t=4.62, P<0.01]. Intragastric administration of retigabine (KCNQ channels opener) to CCD rats alleviated mechanical hyperalgesia [(6.22±1.52)g, (3.90±1.14)g; t=2.57, P<0.05].

Conclusions

The findings elucidated downregulation of the expression and activity of KCNQ2/3/5 channels in DRG neurons of CCD rats contributes to hyperalgesia.Retigabine exhibits an analgesic effect on mechanical allodynia by increasing the M current of DRG neurons of CCD rats.

表1 CCD组与假手术组大鼠机械痛觉阈值时间变化趋势(g,±s)
表2 CCD组与假手术组大鼠DRG组织KCNQ2/3/5 mRNA表达水平的比较(±s)
表3 CCD组与假手术组大鼠DRG组织KCNQ2/3/5蛋白表达水平的比较(g,±s)
表4 瑞替加滨组与PBS组大鼠机械痛觉阈值的比较(g,±s)
[1]
Belkouch M,Dansereau MA,Tétreault P, et al.Functional up-regulation of Nav1.8 sodium channel in Aβ afferent fibers subjected to chronic peripheral inflammation[J]. J Neuroinflammation, 2014(11): 45.
[2]
Ma C,LaMotte RH.Enhanced excitability of dissociated primary sensory neurons after chronic compression of the dorsal root ganglion in the rat[J]. Pain, 2005, 113(1-2): 106-112.
[3]
Zheng Q,Fang D,Liu M, et al.Suppression of KCNQ/M (Kv7) potassium channels in dorsal root ganglion neurons contributes to the development of bone cancer pain in a rat model[J]. Pain, 2013, 154(3): 434-448.
[4]
Delmas P,Brown DA.Pathways modulating neural KCNQ/M (Kv7) potassium channels[J]. Nat Rev Neurosci, 2005, 6(11): 850-862.
[5]
Linley JE,Rose K,Patil M, et al.Inhibition of M current in sensory neurons by exogenous proteases:a signaling pathway mediating inflammatory nociception[J]. J Neurosci, 2008, 28(44): 11240-11249.
[6]
Hirano K,Kuratani K,Fujiyoshi M, et al.Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice[J]. Neurosci Lett, 2007, 413(2): 159-162.
[7]
Bi Y,Chen H,Su J, et al.Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice[J]. Mol Pain, 2011(7): 84.
[8]
Ma C,Shu Y,Zheng Z, et al.Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons[J]. J Neurophysiol, 2003, 89(3): 1588-1602.
[9]
Chaplan SR,Bach FW,Pogrel JW, et al.Quantitative assessment of tactile allodynia in the rat paw[J]. J Neurosci Methods, 1994, 53(1): 55-63.
[10]
Ma C,LaMotte RH.Multiple sites for generation of ectopic spontaneous activity in neurons of the chronically compressed dorsal root ganglion[J]. J Neurosci, 2007, 27(51): 14059-14068.
[11]
Yao H,Donnelly DF,Ma C, et al.Upregulation of the hyperpolarization-activated cation current after chronic compression of the dorsal root ganglion[J]. J Neurosci, 2003, 23(6): 2069-2074.
[12]
Tan ZY,Donnelly DF,LaMotte RH.Effects of a chronic compression of the dorsal root ganglion on voltagegated Na + and K + currents in cutaneous afferent neurons[J]. J Neurophysiol, 2006, 95(2): 1115-1123.
[13]
Fan N,Donnelly DF,LaMotte RH.Chronic compression of mouse dorsal root ganglion alters voltage-gated sodium and potassium currents in medium-sized dorsal root ganglion neurons[J]. J Neurophysiol, 2011, 106(6): 3067-3072.
[14]
Zaika O,Lara LS,Gamper N, et al.Angiotensin II regulates neuronal excitability via phosphatidylinositol 4, 5-bisphosphate-dependent modulation of Kv7 (M-type)K channels[J]. J Physiol, 2006, 575(Pt1): 49-67.
[15]
Mucha M,Ooi L,Linley JE, et al.Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability[J]. J Neurosci, 2010, 30(40): 13235-13245.
[16]
Wang T,Hurwitz O,Shimada SG, et al.Chronic compression of the dorsal root ganglion enhances mechanically evoked pain behavior and the activity of cutaneous nociceptors in mice[J]. PLoS One, 2015, 10(9): e0137512.
[17]
Bal M,Zhang J,Hernandez CC, et al.Ca2+/calmodulin disrupts AKAP79/150 interactions with KCNQ (M-Type) K channels[J]. J Neurosci, 2010, 30(6): 2311-2323.
[18]
Jia Z,Bei J,Rodat-Despoix L, et al.NGF inhibits M/KCNQ currents and selectively alters neuronal excitability in subsets of sympathetic neurons depending on their M/KCNQ current background[J]. J Gen Physiol, 2008, 131(6): 575-587.
[19]
Linley JE,Pettinger L,Huang D, et al.M channel enhancers and physiological M channel block[J]. J Physiol, 2012, 590(4): 793-807.
[20]
Hayashi H,Iwata M,Tsuchimori N, et al.Activation of peripheral KCNQ channels attenuates inflammatory pain[J]. Mol Pain, 2014(10): 15.
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