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，与周围炎症和神经损伤相关的初级传入神经元中某些同种异构体的分布和表达发生了变化。这些改变暗示动态NaCh表达是炎症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被拔出，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NaCh表达与各种刺激的受体表达的可能相关性。本研究的总体目的是在正常和患病的人拔牙中，NaCh表达的变化与冷热感受器对疼痛水平和冷热刺激的临床反应的变化之间的关系。NaCh和热感受器的表达将在正常和模态特异性疼痛组的病变牙齿中进行量化。我们推测疼痛牙中NaCh异构体的表达是动态变化的，并且与正常牙相比，这些变化在时间和空间上与热敏感或冷敏感牙齿中合适的热感受器的表达相关。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疼痛状态和患病人体组织在分子水平上的改变之间可能的相关性。本研究的发现将进一步加深我们对基本疼痛机制和病变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。

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.