DENTAL & OROFACIAL PAIN: BRAINSTEM & THALAMIC MECHANISMS

描述（改编自申请人的摘要）：我们的长期目标 NIH支持的研究是阐明中枢机制和神经可塑性 过程潜在的急性和慢性牙齿和口面疼痛条件和 他们的控制。我们最近的数据显示牙髓诱导的神经可塑性 大鼠口侧亚核脑干伤害性感受神经元的变化 涉及N-甲基-D-天冬氨酸（NMDA）机制的尾侧肌。这些变化 似乎反映了一个类似于最近的“中枢敏感化”的过程， 在脊髓伤害性通路中描述， 痛觉过敏的发展以及可能发生的疼痛的扩散和转移 在损伤和周围组织的炎症之后。的相对重要性 口侧和尾侧的中枢表达和调制这些 然而，伤害性现象仍然不清楚，并且存在非常有限的 丘脑伤害性机制和神经可塑性的信息 与牙髓疼痛的中枢调节有关。鉴于证据确凿的 尾侧肌在口面疼痛机制中的作用及其对 丘脑和口腔，以及脑干和丘脑的有限信息 神经可塑性，建议使用单神经元记录麻醉 大鼠，以解决假设一：牙髓诱导的神经可塑性变化， 口侧亚核伤害性感受神经元可出现在丘脑腹基底核 神经元和依赖于尾侧亚核;和假设II： 牙髓诱发的神经元放电，而不是牙髓诱导的神经可塑性变化， 丘脑腹基底核神经元主要依赖于口亚核。的 将记录腹基底丘脑神经元的特性， 大鼠磨牙牙髓刺激伴或不伴尾侧肌或口侧肌断裂 以确定神经可塑性变化是否表现在丘脑伤害性感受中， 神经元和非伤害感受神经元，如果这些改变了其他神经元， 属性取决于尾肌或口肌。假设三：牙髓诱发 口侧亚核伤害感受神经元的神经可塑性变化， 牙髓诱发的口腔神经元放电依赖于亚核。的 将类似地评估口神经元的特性以确定 牙髓诱导的口腔神经可塑性变化和其他神经元特性， 依赖于尾肌该项目将提供进一步的新见解， 牙髓传入信息的中枢处理及其与 口面疼痛和炎症。

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.