Sodium Channel Expression in Human Teeth

描述(申请人提供)：电压门控钠通道对神经动作电位的起始和传播至关重要，一些钠通道(NACH)亚型优先在初级传入伤害性感受器中表达。实验动物和一些人类研究表明，与外周炎症和神经损伤相关的初级传入神经元中某些亚型的分布和表达发生了变化。这些变化表明，NACH的动态表达是导致炎性和神经病理性疼痛的基本机制。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。正常智齿和被诊断为不可逆转牙髓炎和已知疼痛程度的患病牙齿通常被提取，为分析提供了充足的组织供应。对感觉刺激的反应可以在提取之前进行评估，从而可能使NACH的表达与各种刺激的受体表达相关联。这项研究的总体目标是将正常和疾病拔除的牙齿中NACH表达的变化与热和冷热感受器的变化与疼痛水平和临床反应之间的关系进行关联。NACH和温度感受器的表达将在正常和疾病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亚型的表达发生动态变化，而且与正常牙齿相比，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。在更广泛的意义上，拔除的牙齿代表了一个强大的模型系统，以定量的方式在分子水平上评估已知疼痛状态与疾病人体组织变化之间的可能相关性。这项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了解，这可能是对牙科护理利用的主要威慑。

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.