Sodium Channel Expression in Human Teeth

人类牙齿中钠通道的表达

• 批准号: 7002348
• 负责人: MICHAEL A HENRY
• 金额: $ 35.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7002348
• 关键词: clinical research; cold temperature; dental caries; dental pulp; dental structure; electron microscopy; gene expression; heat stimulus; human subject; immunoperoxidase; laboratory rabbit; patient oriented research; protein isoforms; protein localization; receptor expression; sodium channel; stimulus /response; thermoreceptors; tooth; tooth extraction

DESCRIPTION (provided by applicant): Voltage-gated sodium channels are critical to the initiation and propagation of nerve action potentials and some sodium channel (NaCh) isoforms are preferentially expressed in primary afferent nociceptors. Experimental animal and a few human studies have shown changes in the distribution and expression of certain isoforms within primary afferent neurons associated with peripheral inflammation and following nerve injury. These alterations implicate dynamic NaCh expression as a basic underlying mechanism contributing to inflammatory and neuropathic pain. The tooth pulp is a rich source of pain fibers and represents a valuable model system to study pain mechanisms. Normal wisdom teeth and diseased teeth with a diagnosis of irreversible pulpitis and known pain levels are commonly extracted, providing an ample supply of tissues for analysis. The responses to sensory stimuli can be evaluated prior to extraction, thus allowing a possible correlation of NaCh expression with receptor expression for various stimuli. The overall objective of this study is to correlate changes in NaCh expression with changes in hot and cold thermoreceptors to pain levels and clinical responses to hot and cold stimuli in normal and diseased human extracted teeth. NaCh and thermoreceptor expressions will be quantified in normal and in modaUty-specific pain groups of diseased teeth. We hypothesize that in painful teeth the expression of NaCh isoforms dynamically changes, and further that these changes will correlate temporally and spatially with the expression of appropriate thermoreceptors in hot or cold sensitive painful teeth when compared to normal teeth. In a more general sense, the extracted tooth represents a powerful model system to evaluate in a quantitative fashion a possible correlation between known pain states and the alterations in diseased human tissues at the molecular level. Findings from this study will further our knowledge regarding both basic pain mechanisms and the increased occurrence of local anesthesia failures in diseased teeth that can be a major deterrent for utilization of dental care.

描述（由申请人提供）：电压门控钠通道对于神经动作电位的启动和传播至关重要，并且一些钠通道（NaCh）亚型优先在初级传入伤害感受器中表达。实验动物和一些人类研究表明，初级传入神经元内某些亚型的分布和表达发生变化，与周围炎症和神经损伤后相关。这些改变表明动态 NaCh 表达是导致炎症和神经性疼痛的基本机制。牙髓是疼痛纤维的丰富来源，是研究疼痛机制的有价值的模型系统。通常会拔除正常的智齿和诊断为不可逆牙髓炎且疼痛程度已知的患病牙齿，从而提供充足的组织用于分析。可以在提取之前评估对感觉刺激的反应，从而允许 NaCh 表达与各种刺激的受体表达可能存在相关性。本研究的总体目标是将 NaCh 表达的变化与冷热温度感受器的变化与正常和患病人类拔牙中的疼痛水平以及对冷热刺激的临床反应联系起来。 NaCh 和温度感受器的表达将在正常和病变牙齿的特定疼痛组中进行量化。我们假设在疼痛的牙齿中，NaCh 同工型的表达动态变化，并且进一步认为，与正常牙齿相比，这些变化将在时间和空间上与热或冷敏感的疼痛牙齿中适当的温度感受器的表达相关。从更一般的意义上来说，拔出的牙齿代表了一个强大的模型系统，可以在分子水平上以定量方式评估已知疼痛状态与患病人体组织变化之间的可能相关性。这项研究的结果将进一步加深我们对基本疼痛机制和患病牙齿局部麻醉失败发生率增加的认识，这可能是牙科护理利用的主要障碍。