NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
基本信息
- 批准号:7434558
- 负责人:
- 金额:$ 34.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-15 至 2012-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAfferent NeuronsAgonistBehaviorBehavioralBiological AssayBioluminescenceCell CommunicationCellsChronicChronic intense painCitric Acid CycleCommunicationComplexConditionDevelopmentDiseaseDyesElectric StimulationEndocytosisEnzyme-Linked Immunosorbent AssayEnzymesExocytosisFaceFeedbackFire - disastersFreund&aposs AdjuvantFutureGangliaGeneticGoalsImage AnalysisImmunosorbentsIn VitroInflammationInflammatoryInjuryIon ChannelJawKnowledgeLinkMaintenanceMeasuresMediatingMembraneMethodsMonitorMyxoid cystNerveNerve FibersNeuraxisNeurogliaNeuronsNeuropathyNociceptionNucleotidesOrofacial PainP2X-receptorPainPain DisorderPatientsPatternPeripheralPeripheral NervesPersonal SatisfactionPlant RootsPlayProductionPublic HealthPurinoceptorRattusRecombinantsResearchResearch PersonnelRoleSensorySignal TransductionSkinSmall Interfering RNASpinal CordSpinal GangliaStructureStructure of trigeminal ganglionTRPV1 geneTestingTetanus ToxinTherapeuticTimeTooth structureTumor Necrosis Factor-alphaTumor Necrosis FactorsVanilloidViralVisceraautocrinebasechronic paincytokinedesignganglion cellhuman TNF proteinimmunocytochemistryin vivoinsightknock-downnerve injuryneuronal cell bodyneuronal excitabilitynociceptive responseorofacialparacrineprogramsreceptorreceptor expressionrepairedresponsesatellite celltransmission processvector
项目摘要
DESCRIPTION (provided by applicant): Recent studies of cytokine actions in the spinal cord and dorsal root ganglia suggest that neuron-glia interactions are important in initiating and maintaining chronic pain states. How this is accomplished remains unclear. Disorders of the orofacial complex often produce intense chronic pain in patients and results in devastating consequences in their well being. The long-term goal of this research is to understand neuron-glia interactions in the trigeminal ganglion (TG), the primary afferent structure for the orofacial region. Our focus will be to understand the critical role that transmitters released from neuronal somata (cell bodies) of TGs play in neuron- satellite glial cell communication. We hypothesize that excessive firing in TG neurons elicits somatic release of ATP from neuronal somata. ATP activates satellite cells and evokes cytokine release from these cells. Cytokines in turn sensitize the neuronal somata and further increase their activity. In vitro and in vivo approaches will be used to test this hypothesis of positive feedback loop. We will (1) identify the transmitters released from neuronal somata of TGs (2) examine the communication between neuron and satellite cells (3) determine the effects of cytokines on P2X and TRPV receptor-mediated responses, (4) examine the action of cytokines on nociceptive responses in rats and determine the possibility of using siRNA to down-regulate receptors involved in neuron-glia communication and thus to relieve orofacial nociception. Normal, inflamed and nerve-ligated rats will be used. Transmitter release and membrane currents will be measured with patch pipettes; intracellular Ca2+ concentrations will be monitored with Ca2+ dyes; expression of P2X and TRPV receptors will be examined with immunocytochemistry and Western analyses. These studies should provide a better understanding of the mechanisms underlying neuron-glia interactions in TGs. The knowledge will be critical for designing better therapies for the treatment of orofacial pain.
描述(由申请人提供):最近对脊髓和背根神经节中细胞因子作用的研究表明,神经元-胶质细胞相互作用对于引发和维持慢性疼痛状态很重要。这是如何实现的仍不清楚。口面部复合体疾病常常给患者带来剧烈的慢性疼痛,并对他们的健康造成毁灭性的后果。这项研究的长期目标是了解三叉神经节(TG)中神经元与胶质细胞的相互作用,三叉神经节是口面部区域的主要传入结构。我们的重点是了解 TG 的神经元胞体(细胞体)释放的发射器在神经元-卫星胶质细胞通信中发挥的关键作用。我们假设 TG 神经元的过度放电会引起神经元胞体释放 ATP。 ATP 激活卫星细胞并引发这些细胞释放细胞因子。细胞因子反过来使神经元胞体敏感并进一步增加其活性。将使用体外和体内方法来测试正反馈循环的这一假设。我们将 (1) 识别 TG 神经元胞体释放的递质 (2) 检查神经元和卫星细胞之间的通讯 (3) 确定细胞因子对 P2X 和 TRPV 受体介导的反应的影响,(4) 检查细胞因子对大鼠伤害性反应的作用,并确定使用 siRNA 下调参与神经元-胶质细胞通讯的受体的可能性,从而缓解 口面部伤害感受。将使用正常、发炎和神经结扎的大鼠。将使用贴片移液器测量发射器释放和膜电流;使用 Ca2+ 染料监测细胞内 Ca2+ 浓度; P2X 和 TRPV 受体的表达将通过免疫细胞化学和 Western 分析进行检查。这些研究应该可以更好地理解 TG 中神经元-胶质细胞相互作用的机制。这些知识对于设计更好的治疗口面部疼痛的疗法至关重要。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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LI-YEN M HUANG其他文献
LI-YEN M HUANG的其他文献
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{{ truncateString('LI-YEN M HUANG', 18)}}的其他基金
Neuronal-Glia Interactions in Trigeminal Ganglia as a Basis for Future Therapy
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
8506629 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
Neuronal-Glia Interactions in Trigeminal Ganglia as a Basis for Future Therapy
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
9265450 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
Neuronal-Glia Interactions in Trigeminal Ganglia as a Basis for Future Therapy
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
8661746 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
7858029 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
7153833 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
7621054 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
8069959 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
NEURON-GLIA INTERACTIONS IN TRIGEMINAL GANGLIA AS A BASIS FOR FUTURE THERAPY
三叉神经节中神经元-胶质细胞的相互作用作为未来治疗的基础
- 批准号:
7258444 - 财政年份:2006
- 资助金额:
$ 34.97万 - 项目类别:
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