Anatomy and Function of TRPM8 and TRPA1 in Nociceptors of Dental Pulp

描述（由申请人提供）：牙痛或牙痛是成人和儿童最常见的疼痛类型之一。疼痛可能很严重，导致日常活动中断，包括错过工作，睡眠不足，饮食问题和情绪改变。引起牙痛的主要机制之一是牙髓炎症或牙髓炎。冷过敏是牙髓炎的标志之一。重要的是，涉及牙齿中冷检测的分子机制是未知的。了解牙髓传入冷伤害感受的神经生物学对于确定牙痛管理的新策略和深入了解冷伤害感受的神经生物学都很重要。多种受体潜在地参与有害和非有害冷的检测和转导，其中两种属于瞬时受体电位家族，TRPM 8和TRPA 1受体。该建议旨在表征牙髓传入，TRPM 8和TRPA 1的表达和功能，以阐明它们在牙齿中转导有害冷的作用。特定目标1A中的研究将使用神经解剖学方法评估支配牙髓的三叉神经感觉神经元群体中TRPM 8和TRPA 1的表达和功能。特定目标1B将利用药理学和遗传学方法，使用钙显微荧光测定法评估投射到牙髓的细胞中的TRPM 8和TRPA 1受体活性。具体目标2将评估TRPM 8和TRPA 1对牙髓的有害冷刺激后三叉神经伤害感受神经元的激活的贡献。由于TRP受体已成为伤害性信号传导和整合的至关重要的受体，因此了解它们在牙髓纤维中的表达和功能是了解最常见的口面疼痛类型之一-牙痛的关键。此外，这些研究将有助于我们了解参与冷伤害感受的受体的神经生物学。

DESCRIPTION (provided by applicant): Odontalgia, or toothache, is one of the most common types of pain experienced by both adults and children. The pain can be severe, leading to disruption of daily activities, including missed work, sleep loss, problems eating, and mood alterations. One of the primary mechanisms contributing to odontalgia is inflammation of the dental pulp, or pulpitis. Cold hypersensitivity is one of the hallmarks of pulpitis. Importantly, te molecular mechanisms involved in cold detection in teeth are unknown. Understanding the neurobiology of cold nociception by dental pulp afferents is important for both identifying new strategies for dental pain management and providing insight into the neurobiology of cold nociception. Multiple receptors are potentially involved in the detection and transduction of noxious and non-noxious cold, two of which belong to the transient receptor potential family, the TRPM8 and TRPA1 receptors. This proposal seeks to characterize pulpal afferents, in respect to TRPM8 and TRPA1 expression and function, in order to explicate their role in transducing noxious cold in teeth. Studies in Specific Aim 1A will evaluate TRPM8 and TRPA1 expression and function in the population of trigeminal sensory neurons innervating dental pulp using neuroanatomical methods. Specific Aim 1B will utilize pharmacologic and genetic approaches to evaluate TRPM8 and TRPA1 receptor activity in cells projecting to dental pulp using calcium microfluorometry. Specific Aim 2 will evaluate the contribution of TRPM8 and TRPA1 to activation of central trigeminal nociceptive neurons upon noxious cold stimulation of dental pulp. As TRP receptors have emerged as critically important receptors for nociceptive signaling and integration, understanding their expression and function in pulpal fibers is key to understanding one of the most common types of orofacial pain, odontalgia. Further, these studies will contribute to our understanding of the neurobiology of receptors involved in cold nociception.