CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy.
CXCR4 chemokine receptor signaling mediates pain in diabetic neuropathy.
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DOI：
10.1186/1744-8069-10-42
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发表时间：
2014-06-25
期刊：
影响因子：
3.3
通讯作者：
Miller RJ
中科院分区：
文献类型：
--
作者：
Menichella DM;Abdelhak B;Ren D;Shum A;Frietag C;Miller RJ
疼痛性糖尿病神经病变（PDN）是一种使人衰弱的综合征，存在于四分之一的糖尿病患者中，对他们的生活质量有重大影响。尽管存在这种显著的患病率和影响，但目前的PDN治疗仅部分有效。此外，PDN的蜂窝机制尚未得到很好的理解。神经性疼痛是由多种现象引起的，包括感觉神经元的持续兴奋性，其降低疼痛阈值，使得在缺乏适当刺激的情况下产生疼痛。在多种动物模型中，趋化因子信号转导与神经病理性疼痛的发病机制有关。因此，我们测试的假设，趋化因子信号介导的DRG神经元过度兴奋与PDN。我们证明，腹膜内注射特异性CXCR 4拮抗剂AMD 3100在两种II型糖尿病动物模型中逆转了PDN。此外，从糖尿病小鼠中急性分离的DRG感觉神经元显示出增强的SDF-1诱导的钙反应。此外，我们证明，CXCR 4受体表达的DRG感觉神经元的一个子集。最后，我们观察到大量表达CXCR 4的炎性细胞浸润到糖尿病小鼠的DRG中。这些数据表明，CXCR 4/SDF-1信号转导介导负责PDN的DRG神经元中钙内流和兴奋性的增强。同时，CXCR 4/SDF-1信号可能协调糖尿病DRG中的炎症，这可能有助于糖尿病疼痛的发展。因此，靶向CXCR 4趋化因子受体可能代表治疗PDN的新干预。
Painful Diabetic Neuropathy (PDN) is a debilitating syndrome present in a quarter of diabetic patients that has a substantial impact on their quality of life. Despite this significant prevalence and impact, current therapies for PDN are only partially effective. Moreover, the cellular mechanisms underlying PDN are not well understood. Neuropathic pain is caused by a variety of phenomena including sustained excitability in sensory neurons that reduces the pain threshold so that pain is produced in the absence of appropriate stimuli. Chemokine signaling has been implicated in the pathogenesis of neuropathic pain in a variety of animal models. We therefore tested the hypothesis that chemokine signaling mediates DRG neuronal hyperexcitability in association with PDN. We demonstrated that intraperitoneal administration of the specific CXCR4 antagonist AMD3100 reversed PDN in two animal models of type II diabetes. Furthermore DRG sensory neurons acutely isolated from diabetic mice displayed enhanced SDF-1 induced calcium responses. Moreover, we demonstrated that CXCR4 receptors are expressed by a subset of DRG sensory neurons. Finally, we observed numerous CXCR4 expressing inflammatory cells infiltrating into the DRG of diabetic mice. These data suggest that CXCR4/SDF-1 signaling mediates enhanced calcium influx and excitability in DRG neurons responsible for PDN. Simultaneously, CXCR4/SDF-1 signaling may coordinate inflammation in diabetic DRG that could contribute to the development of pain in diabetes. Therefore, targeting CXCR4 chemokine receptors may represent a novel intervention for treating PDN.
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影响因子：
3.3
作者：
Bhangoo SK;Ripsch MS;Buchanan DJ;Miller RJ;White FA
通讯作者：
White FA
影响因子：
2.6
作者：
Quilici S;Chancellor J;Löthgren M;Simon D;Said G;Le TK;Garcia-Cebrian A;Monz B
通讯作者：
Monz B
影响因子：
2.5
作者：
Ma, C;Shu, YS;LaMotte, RH
通讯作者：
LaMotte, RH
影响因子：
5.8
作者：
Doupis, John;Lyons, Thomas E.;Veves, Aristidis
通讯作者：
Veves, Aristidis
DOI：
10.1073/pnas.1209294110
发表时间：
2012-12-11
影响因子：
11.1
作者：
Miller, Rachel E.;Tran, Phuong B.;Malfait, Anne-Marie
通讯作者：
Malfait, Anne-Marie