Sodium Channel Expression in Human Teeth

描述（由申请人提供）：电压门控钠通道对神经动作电位的启动和传播至关重要，一些钠通道（NaCh）亚型优先在初级传入伤害感受器中表达。实验动物和一些人体研究表明，与外周炎症和神经损伤相关的初级传入神经元内某些亚型的分布和表达发生变化。这些改变暗示动态NaCh表达是促成炎性和神经性疼痛的基本潜在机制。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。正常智齿和诊断为不可逆牙髓炎和已知疼痛程度的患病牙齿通常会被拔除，为分析提供充足的组织供应。可以在提取之前评估对感觉刺激的反应，从而允许NaCl2表达与各种刺激的受体表达的可能相关性。本研究的总体目标是将NaCh表达的变化与冷热热感受器对疼痛水平的变化以及对正常和患病人类拔牙中冷热刺激的临床反应相关联。将在患病牙齿的正常和模式特异性疼痛组中定量NaCh和温度感受器表达。我们假设，在疼痛的牙齿的表达的氯化钠异构体的动态变化，并进一步，这些变化将在时间和空间上与适当的热或冷敏感的疼痛的牙齿相比，正常牙齿的温度感受器的表达。在更一般的意义上，拔牙代表了一个强大的模型系统，以定量的方式评估已知的疼痛状态和分子水平上患病人体组织的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，这可能是利用牙科护理的主要障碍。

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.