Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation.
Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation.
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抑制胱硫醚β-合成酶可抑制腰椎间盘突出症大鼠背根神经节神经元的钠通道活性。
DOI：
10.1038/srep38188
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Yan J;Hu S;Zou K;Xu M;Wang Q;Miao X;Yu SP;Xu GY
腰椎间盘突出症(LDH)疼痛的发病机制尚不清楚。我们最近在大鼠LDH模型上证明了背根神经节(DRG)神经元的电压门控性钠通道(VGSCs)是致敏的。然而，VGSCs致敏的详细分子机制在很大程度上仍不清楚。本研究旨在探讨内源性硫化氢合成酶胱硫醚β合成酶(CBS)在大鼠乳酸脱氢模型增敏VGSCs中的作用。在此，我们发现O-(羧甲基)羟胺半盐酸盐(AOAA)抑制CBS活性可显著减轻LDH大鼠的痛敏反应。AOAA还可降低支配DRG神经元的兴奋性，抑制钠电流密度，并使DII逆行标记的后爪DRG神经元失活曲线的V1/2右移。AOAA体外孵育不改变急性分离的DRG神经元的兴奋性。此外，CBS与Nav1.7和NaV1.8共同定位于支配后爪的DRG神经元。AOAA可显著抑制LDH大鼠背根神经节Nav1.7和NaV1.8的表达。这些数据表明，以DRG水平的CBS-H2S信号为靶点可能是缓解LDH患者慢性疼痛的一种新的治疗策略。
The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH.
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影响因子：
3.3
作者：
Feng X;Zhou YL;Meng X;Qi FH;Chen W;Jiang X;Xu GY
通讯作者：
Xu GY
影响因子：
3.3
作者：
Li L;Xie R;Hu S;Wang Y;Yu T;Xiao Y;Jiang X;Gu J;Hu CY;Xu GY
通讯作者：
Xu GY
多硫化物通过在小鼠感觉神经元中激活伤害性TRPA1引起急性疼痛。
影响因子：
3.3
作者：
Hatakeyama Y;Takahashi K;Tominaga M;Kimura H;Ohta T
通讯作者：
Ohta T
影响因子：
2
作者：
Kataoka, H;Horiyama, S;Ito, Y
通讯作者：
Ito, Y
影响因子：
29.4
作者：
Schicho, Rudolf;Krueger, Dagmar;Schemann, Michael
通讯作者：
Schemann, Michael