Sensitization of P2X3 receptors by cystathionine β-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation.
Sensitization of P2X3 receptors by cystathionine β-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation.
复制标题
胱硫醚β-合成酶对 P2X3 受体的敏化介导腰椎间盘突出症大鼠模型的持续性疼痛超敏反应。
DOI：
10.1186/s12990-015-0012-7
复制
发表时间：
2015-03-20
期刊：
影响因子：
3.3
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Wang Q;Zhu H;Zou K;Yuan B;Zhou YL;Jiang X;Yan J;Xu GY
腰椎间盘突出症（LDH）是椎间盘源性腰痛和坐骨神经痛的主要原因，但其潜在机制仍不清楚。硫化氢（H2S）因其参与包括炎症和伤害感受在内的各种过程而被公认。本研究旨在探讨H2S信号通路在LDH大鼠背根神经节（dorsal root ganglion，DRG）嘌呤能受体（purinergic receptor，P2 XRs）表达和功能调节中的作用。将大鼠尾髓核植入腰5和腰6脊神经根诱导LDH。植入自体NP引起持续性疼痛超敏反应，这是部分逆转鞘内注射A317491，P2 X3受体和P2 X2/3Rs的有效抑制剂。NP诱导的持续性疼痛超敏反应与L5-6 DRG中P2 X3 Rs的表达增加相关，但与P2 X1 Rs和P2 X2 Rs受体的表达无关。与对照组相比，NP植入后DRG神经元ATP诱导的胞内钙信号增加2倍（P < 0.05）。有趣的是，NP植入显著增强了内源性硫化氢产生酶胱硫醚-β-合成酶（CBS）的表达。全身给予CBS抑制剂O-（羧甲基）羟胺半盐酸盐（AOAA）可抑制P2 X3 R表达上调和ATP诱导的DRG神经元胞内钙信号增强（P < 0.05）。鞘内注射AOAA可明显减轻NP引起的持续性疼痛超敏反应.我们的研究结果表明，P2 X3 Rs的敏化，这可能是介导的CBS-H2S信号在初级感觉神经元，有助于椎间盘源性疼痛。靶向CBS/H2S-P2 X3 R信号传导可能代表LDH引起的神经性疼痛的潜在治疗。
Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2X3Rs and P2X2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2X3Rs, but not P2X1Rs and P2X2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2X3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced- persistent pain hypersensitivity. Our results suggest that sensitization of P2X3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2X3R signaling may represent a potential treatment for neuropathic pain caused by LDH.
登录
查看更多内容
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
影响因子：
3
作者：
Miyoshi, Shinji;Sekiguchi, Miho;Kanaya, Fuminori
通讯作者：
Kanaya, Fuminori
影响因子：
14.5
作者：
Kaan, Timothy K. Y.;Yip, Ping K.;McMahon, Stephen B.
通讯作者：
McMahon, Stephen B.
影响因子：
64.8
作者：
Gu, JGG;MacDermott, AB
通讯作者：
MacDermott, AB