DENTAL & OROFACIAL PAIN: BRAINSTEM & THALAMIC MECHANISMS

描述(摘自申请者的摘要)：我们的长期目标 美国国立卫生研究院支持的研究旨在阐明中枢机制和神经可塑性 急性和慢性牙科和口腔面部疼痛的潜在过程和 他们的控制力。我们最近的数据显示，牙髓诱导的神经整形 大鼠口亚核和下丘脑伤害性感受神经元的变化 尾部，涉及N-甲基-D-天冬氨酸(NMDA)机制。这些变化 似乎反映了一个类似于最近的“中枢敏化”的过程 在脊髓伤害性通路中描述的，已经被牵连到 可能发生的痛觉过敏的发展以及疼痛的扩散和转介 外周组织损伤和炎症后。相对重要的是 口腔和尾侧对这些神经元的中枢表达和调控 然而，伤害性现象仍然不清楚，而且非常有限 丘脑伤害性机制和神经可塑性的研究进展 与牙髓痛的中枢调节有关。考虑到有很好的记录 尾肌在口面部疼痛机制中的作用及其直接投射 丘脑和口腔，以及关于脑干和丘脑的有限信息 神经可塑性，建议在麻醉状态下使用单个神经元记录 大鼠，解决假设I：牙髓诱导的神经可塑性变化 口亚核伤害性神经元可见于丘脑腹基底核 神经元，并依赖于尾侧亚核；和假设II： 牙髓诱发的神经元放电，但不是牙髓诱导的神经可塑性改变 丘脑腹基底核神经元主要依赖于口腔亚核。这个 前后丘脑腹基底区神经元的特性将被记录下来 有或无尾部或口部断裂的大鼠磨牙髓刺激 确定丘脑伤害性感受器是否表现为神经可塑性改变 神经元和非伤害性神经元，如果这些改变了其他神经元 属性取决于尾肌或口肌。假设III：牙髓诱导 口侧亚核伤害性神经元的可塑性改变 牙髓诱发的口腔神经元放电依赖于亚核。这个 口腔神经细胞的特性也将进行类似的评估，以确定 牙髓诱导的口腔神经可塑性改变和其他神经元特性 依赖尾肌的。该项目将提供对 牙髓传入信息的中央加工及其与脑电活动的关系 面部疼痛和发炎。

DESCRIPTION (adapted from applicant's abstract): The long-term objective of our NIH-supported research is to elucidate the central mechanisms and neuroplastic processes underlying acute and chronic dental and orofacial pain conditions and their control. Our recent data have revealed tooth pulp-induced neuroplastic changes in nociceptive brainstem neurons of the rat subnucleus oralis and caudalis that involve N-methyl-D-aspartate (NMDA) mechanisms. These changes appear to reflect a process analogous to the "central sensitization" recently described in spinal nociceptive pathways that has been implicated in the development of the hyperalgesia and spread and referral of pain that may occur after injury and inflammation of peripheral tissues. The relative importance of oralis and caudalis to the central expression and modulation of these nociceptive phenomena is however still unclear, and there is very limited information available of thalamic nociceptive mechanisms and neuroplasticity associated with the central mediation of pulp pain. Given the well-documented role of caudalis in orofacial pain mechanisms and its direct projections to both thalamus and oralis, and the limited information on brainstem and thalamic neuroplasticity, it is proposed to use single neuron recordings in anesthetized rats, to address Hypothesis I: The pulp-induced neuroplastic changes in subnucleus oralis nociceptive neurons can be manifested in ventrobasal thalamic neurons and are dependent on subnucleus caudalis; and Hypothesis II: Pulp-evoked neuronal discharges but not pulp-induced neuroplastic changes in ventrobasal thalamic neurons are primarily dependent on subnucleus oralis. The properties of ventrobasal thalamic neurons will be documented before and after molar pulp stimulation in rats with or without disruption of caudalis or oralis to determine if neuroplastic changes are manifested in thalamic nociceptive neurons and non-nociceptive neurons and if these changes an other neuronal properties are dependent on caudalis or oralis. Hypothesis III: Pulp-induced neuroplastic changes in subnucleus oralis nociceptive neurons but not pulp-evoked oralis neuronal discharges are dependent on subnucleus. The properties of oralis neurons will similarly be assessed to determine if the pulp-induced oralis neuroplastic changes and other neuronal properties are dependent on caudalis. This project will provide further new insights into the central processing of pulp afferent information and its relationship to orofacial pain and inflammation.